Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

by The PLOS ONE Editors …

by Roxana Hossain, Glenda Willems, Niels Wynant, Simon Borgolte, Kristof Govaerts, Mark Varrelmann Beet yellows virus (BYV), one of the causal agents of virus yellows (VY) disease in sugar beet (Beta vulgaris subsp. vulgaris), induces economically important damage to the sugar production in Europe. In the absence of effective natural resistance traits, a deeper understanding of molecular reactions in plants to virus infection is required. In this study, the transcriptional modifications in a BYV susceptible sugar beet genotype following aphid-mediated inoculation on mature leaves were studied at three early infection stages [6, 24 and 72 hours post inoculation (hpi)] using RNA sequencing libraries. On average, 93% of the transcripts could be mapped to the B. vulgaris reference genome RefBeet-1.2.2. In total, 588 differentially expressed genes (DEGs) were identified across the three infection stages. Of these, 370 were up- regulated and 218 down-regulated when individually compared to mock-aphid inoculated leaf samples at the same time point, thereby eliminating the effect of aphid feeding itself. Using MapMan ontology for categorisation of sugar beet transcripts, early differential gene expression identified importance of the BIN categories “enzyme classification”, “RNA biosynthesis”, “cell wall organisation” and “phytohormone action”. A particularly high transcriptional change was found for diverse transcription factors, cell wall regulating proteins, signalling peptides and transporter proteins. 28 DEGs being important in “nutrient uptake”, “lipid metabolism”, “phytohormone action”, “protein homeostasis” and “solute transport”, were represented at more than one infection stage. The RT-qPCR validation of thirteen selected transcripts confirmed that BYV is down-regulating chloroplast-related genes 72 hpi, putatively already paving the way for the induction of yellowing symptoms characteristic for the disease. Our study provides deeper insight into the early interaction between BYV and the economically important crop plant sugar beet and opens up the possibility of using the knowledge of identified proviral plant factors as well as plant defense-related factors for resistance breeding.

by Jooyeon Park, Kyoung Hwa Lee, Young Goo Song, Hyungmin Park, Kwang Suk Lee Since the COVID-19 pandemic, there has been persistent emphasis on the importance of indoor air disinfection and ventilation in isolation units in the hospital environment. Nevertheless, no optimal and concrete disinfection protocol has been proposed to inactivate the viruses as quickly as possible. In this study, we experimentally evaluated various ventilation and disinfection protocols based on the combination of negative-pressure ventilation, ultraviolet (UV) light illumination, and Hypochlorous acid (HOCl) spray against three active virus species in a 3.5 cubic meters isolation unit. This small-size unit has gained attention during the pandemic due to the high demand for compact mobile laboratory systems capable of rapid disease diagnosis. In accordance with the WHO laboratory biosafety guidance, which states that all enclosed units where diagnostic work is conducted must ensure proper ventilation and disinfection activities, we aim to propose virus removal protocols for units compact enough to be installed within a van or deployed outdoor. The results confirmed the superiority (in terms of virus removal rate and time required) of the virus removal methods in the order of UV light, ventilation, and HOCl spray. Ultimately, we propose two optimal protocols: (i) UV light alone for three minutes, and (ii) UV light with ventilation for three minutes, followed by one-minute ventilation only. The time span of three minutes in the latter protocol is based on the clinical practice such that the medical staffs have a sufficient time to process the samples taken in transition to next patient to care.

by Marie Y. Detrait, Stéphanie Warnon, Raphaël Lagasse, Laurent Dumont, Stéphanie De Prophétis, Amandine Hansenne, Juliette Raedemaeker, Valérie Robin, Géraldine Verstraete, Aline Gillain, Nicolas Depasse, Pierre Jacmin, Delphine Pranger Introduction Primary refractory disease affects 30–40% of patients diagnosed with DLBCL and is a significant challenge in disease management due to its poor prognosis. Predicting refractory status could greatly inform treatment strategies, enabling early intervention. Various options are now available based on patient and disease characteristics. Supervised machine-learning techniques, which can predict outcomes in a medical context, appear highly suitable for this purpose. Design Retrospective monocentric cohort study. Patient population Adult patients with a first diagnosis of DLBCL admitted to the hematology unit from 2017 to 2022. Aim We evaluated in our Center five supervised machine-learning (ML) models as a tool for the prediction of primary refractory DLBCL. Main results One hundred and thirty patients with Diffuse Large B-cell lymphoma (DLBCL) were included in this study between January 2017 and December 2022. The variables used for analysis included demographic characteristics, clinical condition, disease characteristics, first-line therapy and PET-CT scan realization after 2 cycles of treatment. We compared five supervised ML models: support vector machine (SVM), Random Forest Classifier (RFC), Logistic Regression (LR), Naïve Bayes (NB) Categorical classifier and eXtreme Gradient Boost (XGboost), to predict primary refractory disease. The performance of these models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, false positive rate, sensitivity, and F1-score to identify the best model. After a median follow-up of 19.5 months, the overall survival rate was 60% in the cohort. The Overall Survival at 3 years was 58.5% (95%CI, 51–68.5) and the 3-years Progression Free Survival was 63% (95%CI, 54–71) using Kaplan-Meier method. Of the 124 patients who received a first line treatment, primary refractory disease occurred in 42 patients (33.8%) and 2 patients (1.6%) experienced relapse within 6 months. The univariate analysis on refractory disease status shows age (p = 0.009), Ann Arbor stage (p = 0.013), CMV infection (p = 0.012), comorbidity (p = 0.019), IPI score (p…

by Viet Q. Dao, Crystal N. Johnson, William J. Platt Processes modifying newly deposited litter substrates should affect fine fuels in fire-managed tidal marsh ecosystems. Differences in chemical composition and dynamics of litter should arise from fire histories that generate pyrodiverse plant communities, tropical cyclones that deposit wrack as litter, tidal inundation that introduces and alters sediments and microbes, and interactions among these different processes. The resulting diversity and dynamics of available litter compounds should affect microbial (fungal and bacterial) communities and their roles in litter substrate dynamics and ecosystem responses over time. We experimentally examined effects of differences in litter types produced by different fire regimes and litter loads (simulating wrack deposition) on microbial community composition and changes over time. We established replicated plots at similar elevations within frequent tidal-inundation zones of a coastal brackish Louisiana marsh. Plots were located within blocks with different prescribed fire regimes. We deployed different measured loads of new sterilized litter collected from zones in which plots were established, then re-measured litter masses at subsequent collection times. We used DNA sequencing to characterize microbial communities, indicator families, and inferred ecosystem functions in litter subsamples. Differences in fire regimes had large, similar effects on fungal and bacterial indicator families and community compositions and were associated with alternate trajectories of community development over time. Both microbial and plant community compositional patterns were associated with fire regimes, but in dissimilar ways. Differences in litter loads introduced differences in sediment accumulation associated with tidal inundation that may have affected microbial communities. Our study further suggests that fire regimes and tropical cyclones, in the context of frequent tidal inundation, may interactively generate substrate heterogeneities and alter microbial community composition, potentially modifying fine fuels and hence subsequent fires. Understanding microbial community compositional and functional responses to fire regimes and tropical cyclones should be useful in management of coastal marsh ecosystems.

by Mohammed S. Almuhayawi, Mohammed H. Alruhaili, Mohamed K. Y. Soliman, Muyassar K. Tarabulsi, Ruba A. Ashy, Amna A. Saddiq, Samy Selim, Yasir Alruwaili, Salem S. Salem It is thought to be risk-free, environmentally benign, and safe for biological processes to produce zinc oxide nanoparticles from renewable resources. This study examined Cassia javanica’s ability to create ZnONPs. The generated ZnONPs were analyzed using a variety of techniques, such as TEM, FTIR spectroscopy, UV-Vis spectroscopy, and XRD analysis. The antibacterial potential of ZnONPs has been investigated using both Agar well diffusion and microtitreplate (MTP) methods. One method used to evaluate ZnONPs’ capacity to scavenge free radicals at different concentrations was the DPPH method. The permanent zinc oxide (ZnO) shape and the naturally occurring crystal structure of ZnONPs were validated by the XRD data. ZnONPs showed antibacterial activity with MICs of 31.7 μg/mL toward Bacillus subtilis, 62.5 μg/mL for Salmonella typhimurium, Escherichia coli while Clostridium sporogenes and Bacillus pumilus was 125μg/mL. Furthermore, ZnONPs demonstrated a range of antibiofilm activities toward Staphylococcus aureus (MRSA). ZnONPs showed an intriguing antioxidant capacity, achieving IC50 of 109.3 μg/ml μg/mL. Additionally, ZnONPs demonstrated low toxic effect on Vero cell with IC50 154.01 μg/mL as well as possible anticancer action when applied to the carcinoma cell lines HepG2 with IC50 of 47.48 μg/mL. Furthermore, ZnONPs at 62.5 μg/mL had a promising antiviral impact against HSV1 and COX B4, with antiviral activities of 75.4% and 65.8%, respectively.

by Yichong Zhao, Kenta Oono, Hiroki Takizawa, Masaaki Kotera The design of RNA plays a crucial role in developing RNA vaccines, nucleic acid therapeutics, and innovative biotechnological tools. However, existing techniques frequently lack versatility across various tasks and are dependent on pre-defined secondary structure or other prior knowledge. To address these limitations, we introduce GenerRNA, a Transformer-based model inspired by the success of large language models (LLMs) in protein and molecule generation. GenerRNA is pre-trained on large-scale RNA sequences and capable of generating novel RNA sequences with stable secondary structures, while ensuring distinctiveness from existing sequences, thereby expanding our exploration of the RNA space. Moreover, GenerRNA can be fine-tuned on smaller, specialized datasets for specific subtasks, enabling the generation of RNAs with desired functionalities or properties without requiring any prior knowledge input. As a demonstration, we fine-tuned GenerRNA and successfully generated novel RNA sequences exhibiting high affinity for target proteins. Our work is the first application of a generative language model to RNA generation, presenting an innovative approach to RNA design.

by Noelle M. Nieskens, Yukiko Miyamoto, Brianna M. Hurysz, Anthony J. O’Donoghue, Lars Eckmann Trichomonas vaginalis is the causative agent of the common sexually transmitted disease, trichomoniasis, which affects more than a hundred million people worldwide. Metronidazole and tinidazole, agents belonging to the 5-nitroheterocyclic class of antimicrobials, are most often used to treat infection, but increased resistance has been reported and adverse effects of these drugs can be significant. Consequently, an urgent need exists for the development of novel drug entities against trichomoniasis. Critical for antimicrobial drug development is the demonstration of in vivo efficacy. Murine models of vaginal T. vaginalis infection are unreliable for unknown reasons. Meanwhile, murine infections with the related bovine pathogen, Tritrichomonas foetus, tend to be more robust, although susceptibility to different antimicrobials might differ from T. vaginalis. Here, we explored the utility of T. foetus infection as a surrogate model for drug development against T. vaginalis. Four different T. foetus strains caused robust vaginal infection in young mice, while none of four diverse T. vaginalis strains did. Comparison of drug susceptibility profiles revealed that T. foetus and T. vaginalis were similarly susceptible to a range of 5-nitroheterocyclic and gold(I) compounds. By comparison, proteasome inhibitors were 10- to 15-fold less active against T. foetus than T. vaginalis, although one of the proteasome inhibitors, bortezomib, had low micromolar activity or better against multiple strains of both trichomonads. Different strains of T. foetus were used to demonstrate the utility of the murine vaginal infection models for in vivo efficacy testing, including for bortezomib and a gold(I) compound. The differences in susceptibility to proteasome inhibitors may be partially explained by differences in the proteasome subunit sequences between the two trichomonads, although the functional relevance of the proteasome was similar in both organisms. These findings indicate that T. foetus can serve as a reliable surrogate model for T. vaginalis in vitro and in murine infections in vivo, but caution must be exercised for specific drug classes with targets, such as the proteasome, that may display genetic divergence between the trichomonads.

by Rajkumar Kulandaivel, Manikandan Ramachandran, Sathishkumar Veerappampalayam Easwaramoorthy, Jaehyuk Cho Recent evolution in connected devices modelled a massive stipulation for network traffic resources and classification. Software-defined networking (SDN) enables ML techniques with the Internet of Things (IoT) to automate network traffic. This helps to reduce accuracy and improves latency. Problems by conventional techniques to categorize network traffic acquired from IoT and assign resources can be resolved through SDN solutions. This manuscript proposes a proposed network traffic classification technique on IoT with SDN called Gauss Markov and Flow-balanced Vector Radial Learning (GM-FVRL). With the network traffic features acquired from the IoT devices, SDN-enabled Gauss Markov Correlation-based IoT Network Traffic Feature Extraction is applied to extort relevant network aspects. Next, the flow-balanced radial-based ML model for network traffic categorization uses the relevant extracted network traffic features. With the aid of flow, the balanced radial basis function reduces the influence of noise due to distinct network flow. This helps to improve accuracy and minimize latency. Due to this, better precision and recall is ensured. Performance of our method has been evaluated utilizing a scheme using an SDN traffic dataset. The results show that our method classifies the network traffic with high classification accuracy and minimum latency, ensuring better precision and recall.

Publication date: Available online 30 September 2024 Source: Immunity Author(s): Ye Liu, Yifang Chen, Uyanga Batzorig, Jingting Li, Celia Fernández-Méndez, Samiksha Mahapatra, Fengwu Li, Shebin Sam, Tatsuya Dokoshi, Seung-Phil Hong, Teruaki Nakatsuji, Richard L. Gallo, George L. Sen …

Publication date: Available online 30 September 2024 Source: Immunity Author(s): Alexander Lercher, Jin-Gyu Cheong, Michael J. Bale, Chenyang Jiang, Hans-Heinrich Hoffmann, Alison W. Ashbrook, Tyler Lewy, Yue S. Yin, Corrine Quirk, Emma J. DeGrace, Luis Chiriboga, Brad R. Rosenberg, Steven Z. Josefowicz, Charles M. Rice …

Infection and Immunity, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

BackgroundTwo decades have passed since the beginning of the Iraq War in 2003. Iraq has long suffered from conflicts and instability, where the people have limited access to healthcare. The coronavirus disease (COVID-19) pandemic brought additional disruption to health service provision. ObjectivesAt the midpoint towards universal health coverage (UHC) in 2030, this study aims to gain a better understanding of the trends of UHC progress in Iraq in the context of the conflicts and the COVID-19 pandemic and to indicate possible pragmatic options. DesignThis study employed Bayesian hierarchical regression models to estimate trends and projections of health service availability and coverage indicators up to 2030. Furthermore, for health service coverage, four scenarios were defined based on the availability of health services, and projections were made for each scenario up to 2030. SettingOur approach used the yearly data from the Ministry of Health and four nationally representative household surveys between 2000 and 2020. We evaluated the subnational-level progress in three health service availability indicators and 13 health service coverage indicators in 18 governorates in Iraq from 2000 to 2030. ResultsThe findings from 2000 to 2020 revealed a lack of progress in the indicators of health facility and inpatient bed, and pronounced detrimental effects from major conflicts and the pandemic on all measured health service coverage indicators. Despite these setbacks, several health service coverage indicators demonstrated resilience and elasticity in their recovery. The projected trends for 2021 to 2030 indicated limited alternations in the health service availability. By 2030, five health service coverage indicators will achieve the designated 80% targets. A scenario-based analysis predicts improved coverage of antenatal care, and child immunisation and treatment if health service availability is bolstered to globally recommended standards. Under this scenario, several governorates—Anbar, Baghdad, Nainawa, Qadissiyah, Salahaddin, Thiqar and Wasit—presented improved health service coverage in more indicators. ConclusionStrengthened health service availability has the potential to significantly improve fragile health service coverage indicators and in more vulnerable governorates. …

ObjectiveThis study aimed to evaluate the safety and performance of PowerPICC catheters in a real-world setting. DesignProspective, observational, multicentre study. SettingNine European countries, involving 14 centres. ParticipantsGeneral patient population. InterventionPowerPICC catheter inserted by the clinician as standard of care with routinely collected outcomes followed through device removal or 180 days postinsertion. Primary and secondary outcomes measuresSafety and performance outcomes were assessed for PowerPICC, PowerPICC SOLO 2 and PowerGroshong PICC. The primary safety endpoint was the incidence of symptomatic venous thrombosis (VT), and secondary safety endpoints included phlebitis, extravasation, vessel laceration, vessel perforation local infection, accidental dislodgment and catheter-related bloodstream infection (CRBSI). The primary performance endpoint was the percentage of patients whose PowerPICC device remained in place through the completion of therapy. The secondary performance endpoints included catheter patency, placement success in a single attempt and usability. ResultsThe enrolled patients (N=451) received either PowerPICC, PowerPICC SOLO 2 or PowerGroshong PICC catheters. Across all devices, 1.6% of patients developed symptomatic VT, and CRBSI occurred in 1.6% of patients. There were no cases of phlebitis or extravasation and only three cases of vein laceration or vein perforation. The catheters showed high success rates in completing therapy (81.8%), maintaining patency (93.9%) and achieving successful placement in a single attempt (90.4%). Clinicians overwhelmingly agreed that both the guidewire and stylet (93.3% and 94.4%, respectively) were easy or very easy to use. ConclusionsThis study demonstrates the safety and performance of PowerPICC catheters across diverse settings and patient cohorts in real-world hospital settings across Europe. The findings indicate that these catheters are safe and can be effectively used in the general patient setting and when inserted by a variety of clinicians. The low incidence of complications and high success rates further support the clinical utility of these catheters. Trial registration numberNCT04263649. …

ObjectivesTo validate and test the generalisability of the SASKit-ML pipeline, a prepublished feature selection and machine learning pipeline for the prediction of health deterioration after a stroke or pancreatic adenocarcinoma event, by using it to identify biomarkers of health deterioration in chronic disease. DesignThis is a validation study using a predefined protocol applied to multiple publicly available datasets, including longitudinal data from cohorts with type 2 diabetes (T2D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and various cancers. The datasets were chosen to mimic as closely as possible the SASKit cohort, a prospective, longitudinal cohort study. Data sourcesPublic data were used from the T2D (77 patients with potential pre-diabetes and 18 controls) and IBD (49 patients with IBD and 12 controls) branches of the Human Microbiome Project (HMP), RA Map (RA-MAP, 92 patients with RA, 22 controls) and The Cancer Genome Atlas (TCGA, 16 cancers). MethodsData integration steps were performed in accordance with the prepublished study protocol, generating features to predict disease outcomes using 10-fold cross-validated random survival forests. Outcome measuresHealth deterioration was assessed using disease-specific clinical markers and endpoints across different cohorts. In the HMP-T2D cohort, the worsening of glycated haemoglobin (HbA1c) levels (5.7% or more HbA1c in the blood), fasting plasma glucose (at least 100 mg/dL) and oral glucose tolerance test (at least 140) results were considered. For the HMP-IBD cohort, a worsening by at least 3 points of a disease-specific severity measure, the \'Simple Clinical Colitis Activity Index\' or \'Harvey-Bradshaw Index\' indicated an event. For the RA-MAP cohort, the outcome was defined as the worsening of the \'Disease Activity Score 28\' or \'Simple Disease Activity Index\' by at least five points, or the worsening of the \'Health Assessment Questionnaire\' score or an increase in the number of swollen/tender joints were evaluated. Finally, the outcome for all TCGA datasets was the progression-free interval. ResultsModels for the prediction of health deterioration in T2D, IBD, RA and 16 cancers were produced. The T2D (C-index of 0.633 and Integrated Brier Score (IBS) of 0.107) and the RA (C-index of 0.654 and IBS of 0.150) models were modestly predictive. The IBD model was uninformative. TCGA models tended towards modest predictive power. ConclusionsThe SASKit-ML pipeline produces informative and useful features with the power to predict health deterioration in a variety of diseases and cancers; however, this performance is disease-dependent. …

IntroductionFetal growth restriction (FGR) affects about 3%–5% of term pregnancies. If prenatally detected and anterograde umbilical artery flow is preserved (stage I), it is recommended to deliver at term (≥ 37+0 weeks). In the absence of contraindications, the vaginal route is preferred, and labour induction is usually required. It has been postulated that mechanical methods for cervical ripening may have an optimal profile for the induction of term FGR fetuses since they are associated with less uterine stimulation than the standard pharmacological methods, and therefore, could be better tolerated by fetuses with reduced placental reserve. This study aims to evaluate whether cervical ripening with a Cook’s balloon for the induction of labour from 37+0 weeks of gestation in the stage I FGR manages to increase the rate of vaginal delivery compared with vaginal dinoprostone. Methods and analysisThis will be an open-labelled, randomised, parallel-group clinical trial to be held in five Spanish maternities. Women aged ≥18 years with singleton pregnancies complicated with stage I FGR (defined as the presence of at least one of these two criteria: (1) estimated fetal weight (EFW)

Abstract Background Tuberculous peritonitis often presents with nonspecific symptoms that can lead to diagnostic challenges, particularly when manifesting as peritoneal pseudocysts. This study highlights the clinical complexity and diagnostic approach of tuberculous peritonitis presented as a pseudocyst in an immunocompetent adult, an atypical scenario that is rarely documented. Case presentation We report a detailed case of a 41-year-old man presenting with abdominal distension, pain, and significant weight loss over four months. Abdominal CT showed a peritoneal pseudocyst, initially misdiagnosed due to its resemblance to more common abdominal pathologies. The diagnosis of tuberculous peritonitis was confirmed through histopathological analysis. Additionally, a systematic literature review was conducted to identify and analyse similar cases, focusing on clinical presentations, diagnostic methods, and patient outcomes. Our patient exhibited classic symptoms of abdominal TB but was unique due to the absence of prior ventriculoperitoneal shunting, a common factor in similar cases. Our literature review found that such presentations typically result in diagnostic delays averaging five months, complicating patient management and outcomes. This review also underscores the importance of considering tuberculosis in the differential diagnosis of peritoneal pseudocysts, particularly in TB-endemic regions. Conclusion This case and review emphasize the need for high clinical suspicion and prompt investigation of tuberculosis in patients presenting with atypical abdominal symptoms and pseudocysts. Improved diagnostic strategies, including early use of imaging and pathological evaluations, are essential for timely diagnosis and management, thereby improving patient outcomes in suspected cases of extrapulmonary tuberculosis. …

Abstract Background Omadacycline is a new generation of tetracycline antibiotics, and its clinical application is increasing. We report the first case of acute pancreatitis possibly induced by omadacycline. Case presentation The patient was admitted to the emergency intensive care unit due to community-acquired pneumonia. The initial treatment consisted of meropenem combined with levofloxacin, and the regimen was subsequently switched to omadacycline combined with cefoperazone/sulbactam due to sputum culture showing carbapenem-resistant Acinetobacter baumannii. Seven days after the administration of omadacycline, abdominal tenderness occurred, and CT scan revealed an enlarged gallbladder with exudation from the pancreatic head. The patient was diagnosed with acute pancreatitis and improved after dis-continuing omadacycline. Conclusions Omadacycline, like other tetracycline antibiotics, may cause pancreatitis. Combination medications can be an important factor in this adverse reaction. …

Abstract Background In the pediatric population, Staphylococcus aureus infections are responsible for increased morbidity and mortality, length of hospitalization and the cost of inpatient treatment. The aim of this study is to describe the antimicrobial resistance profile of S. aureus isolated in clinical specimens from pediatric patients admitted to a tertiary hospital in Rio de Janeiro, Brazil. Methods Culture reports and medical records of hospitalized patients under 18 years of age with S. aureus infections between January 2015 and December 2022 were retrospectively analyzed. Information was collected on recent antibiotic use, previous hospital admission, inpatient unit, clinical specimen, time of infection (community or nosocomial), classification according to susceptibility to methicillin (methicillin sensitive - MSSA or methicillin resistant - MRSA) and sensitivity to other antimicrobials. We analyzed the distribution of the sensitivity profile of S. aureus infections over the 7 years evaluated in the study. Results Were included 255 unique clinical episodes, among which the frequencies of MSSA and MRSA were 164 (64%) and 91 (36%), respectively. Over the 7 years evaluated, there was stability in the prevalence percentage, with a predominance of MSSA in the range of 60 to 73.3%, except in 2020, when there was a drop in the prevalence of MSSA (from 73.3% in 2019 to 52.5%) with an increase in MRSA (from 26.7% in 2019 to 47.5%). Ninety-seven (38%) infections were community-acquired and 158 (62%) were healthcare-associated. The main clinical specimens collected were blood cultures (35.2%) and wound secretions (17%). The MRSA isolates presented percentages of sensitivity to trimethoprim-sulfamethoxazole from 90.4 to 100%, and to clindamycin from 77 to 89.8% in MRSA healthcare associated and MRSA community respectively. Conclusion There was a constant predominance in the prevalence of MSSA with percentage values ​​maintained from 2015 to 2022, except in 2020, in which there was a specific drop in the prevalence of MSSA with an increase in MRSA. MSSA infections are still predominant in the pediatric population, but MRSA rates also present significant values, including in community infections, and should be considered in initial empiric therapy. …

Abstract Background and objective To diagnose tuberculosis infection (TBI), whole blood is incubated with M.tuberculosis (Mtb)-specific peptides and the release of interferon-γ (IFN-γ) is measured in IFN-γ-release assays (IGRAs). Hyperglycaemia and fluctuations in blood glucose may modulate IFN-γ-release. Here, we investigated if glucose intake affects IFN-γ-release or IGRA results in IGRAs taken during an oral glucose tolerance test (OGTT). Methods Persons with TB disease (TB) or TBI underwent a standard 75-g OGTT at the start and end of treatment for TB or TBI. Blood for the IGRA QuantiFERON-TB Gold Plus (QFT) containing Mtb-specific tubes (TB1 and TB2), a non-specific mitogen tube (MIT) and an empty control tube (NIL) was drawn at sample-timepoints -15 (baseline), 60, 90, 120 and 240 min during the OGTT. Blood glucose was measured in parallel at all timepoints. IFN-γ-release (after subtraction of NIL) at each timepoint was compared with baseline using linear-mixed-model analysis. Results Twenty-four OGTTs from 14 participants were included in the final analysis. Compared to baseline, IFN-γ-release was increased at sample-timepoint 240 min for TB1; geometric mean (95% confidence interval) 3.0 (1.5–6.2) vs 2.5 (1.4–4.4) IU/mL (p = 0.047), and MIT; 182.6 (103.3–322.9) vs 146.0 (84.0–254.1) IU/mL (p = 0.002). Plasma glucose levels were not associated with IFN-γ-release and the QFT test results were unaffected by the OGTT. Conclusion Ingestion of glucose after a 10-h fast was associated with increased IFN-γ-release after 240 min in the MIT tube. However, there was no association between plasma glucose levels at the QFT sampling timepoint and IFN-γ-release. Furthermore, the QFT test results were not affected by glucose intake. The overall effect of an OGTT and prevailing plasma glucose levels on IFN-γ-release in IGRAs seem limited. Trial registration Trial registration ID: NCT04830462 (https://clinicaltrials.gov/study/NCT04830462). Registration date: 05-Apr-2021. …

Abstract Gallibacterium anatis (G. anatis) is an opportunistic pathogen previously associated with deaths in poultry and is also a pathogen that rarely causes human diseases. G. anatis has only been reported twice as the causative agent of a human disease (both in France). Here, we report a 62-year-old male patient with hypertension and type 2 diabetes who suffered from acute watery diarrhea caused by this bacterium which was identified by MALDI-TOF MS and 16 S rRNA sequencing. Despite human diarrhea caused by G.anatis is rare, with the continuous emergence of multidrug-resistant isolates of G. anatis in recent years, this case report will inform clinicians that G. anatis especially drug-resistant G. anatis may be a possible infectious source of human diarrhea in immune-suppressed populations. …

Abstract Background False negative rapid diagnostic tests (RDTs) accruing to the non-detection of Plasmodium falciparum histidine-rich protein 2/3 (Pfhrp2/3) is threatening the diagnosis and management of malaria. Although regular monitoring is necessary to gauge the level of efficacy of the tool, studies in Cameroon remain limited. This study assessed Plasmodium spp. prevalence and Pfhrp2/3 gene deletions across ecological and transmission zones in Cameroon. Methods This is a cross-sectional, multi-site, community- and hospital- based study, in 21 health facilities and 14 communities covering all five ecological settings in low seasonal (LS) and intense perennial (IPT) malaria transmission zones between 2019 and 2021. Participants were screened for malaria parasite using Pfhrp2 RDT and light microscopic examination of thick peripheral blood smears. DNA was extracted from dried blood spot using chelex®-100 and P. falciparum confirmed using varATS real-time quantitative Polymerase Chain Reaction (qPCR), P. malariae and P. ovale by real-time qPCR of Plasmepsin gene, and P. vivax using a commercial kit. Isolates with amplified Pfcsp and Pfama-1 genes were assayed for Pfhrp 2/3 gene deletions by conventional PCR. Results A total of 3,373 participants enrolled, 1,786 Plasmodium spp. infected, with 77.4% P. falciparum. Discordant RDT and qPCR results (False negatives) were reported in 191 (15.7%) P. falciparum mono-infected samples from LS (29%, 42) and IPT (13.9%, 149). The Pfhrp2+/Pfhrp3 + genotype was most frequent, similar between LS (5.5%, 8/145) and IPT (6.0%, 65/1,076). Single Pfhrp2 and Pfhrp3 gene deletions occurred in LS (0.7%, 1/145 each) and IPT (3.6%, 39/1,076 vs. 2.9%, 31/1,076), respectively. Whilst a single sample harboured Pfhrp2-/Pfhrp3- genotype in LS, 2.4% (26/1,076) were double deleted at IPT. Pfhrp2+/Pfhrp3- (0.3%, 3/1,076) and Pfhrp2-/Pfhrp3+ (1.2%, 13/1,076) genotypes were only observed in IPT. Pfhrp2, Pfhrp3 deletions and Pfhrp2-/Pfhrp3- genotype accounted for 78.8% (26), 69.7% (23) and 63.6% (21) RDT false negatives, respectively. Conclusion Plasmodium falciparum remains the most dominant and widely distributed Plasmodium species across transmission and ecological zones in Cameroon. Although the low prevalence of Pfhrp2/3 gene deletions supports the continued use of HRP2-based RDTs for routine malaria diagnosis, the high proportion of false-negatives due to gene deleted parasites necessitates continued surveillance to inform control and elimination efforts. …

Abstract Introduction Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. Case presentation A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. Conclusion The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates. …

Abstract Introduction HIV self-testing represents a convenient and confidential option for HIV testing—the present study aimed to assess the acceptability of blood versus saliva self-tests among key populations in Kisangani. Methods This study was an analytical cross-sectional study. Our sample size was 363 subjects. After obtaining their consent, we administered a questionnaire to participants. We asked participants to choose between blood and saliva self-testing. We defined the acceptability of the self-test (saliva or blood) as the intention to use the self-test using a 5-point Likert scale. Descriptive statistics were described by estimating proportions for categorical variables and means with standard deviations for symmetrically distributed quantitative variables. The variable of interest was the acceptability of self-testing, which was dichotomized (Very Likely/Unlikely). The corresponding endpoint was the proportion of participants accepting the self-test in HIV screening. A bivariate analysis was performed to determine factors related to the acceptability of the self-test, using Pearson’s Chi-square (χ2) and ANOVA followed by 2-to-2 multiple comparisons (Bonferroni) for comparison of means and proportions. A progressive stepwise logistic regression model at the 5% threshold included variables with a bi-variate association. Results The acceptability of the blood self-test was 71.6% compared to 28.4% for the saliva self-test. Factors associated with acceptability of the self-test were higher level of education aOR CI95%: 1.5(0.4–5.5) p = 0.006; non-use of condoms with casual partners aOR CI95%: 2.8(1.4-5) p = 0.003; knowledge of the type of self-test aOR CI95%:2.4(1.02–5.65) p = 0.043 and the obstacle to acceptability of the self-test was non-availability of the self-test aOR CI 95%: 18.9(6.5–54.9) p 

Abstract Background Since May 7 2022, mpox has been endemic in many countries which has attracted the attention of health authorities in various countries and made control decisions, in which vaccination is the mainstream strategy. However, the shortage of vaccine doses and the reduction of protective efficacy have led to unresolved issues such as vaccine allocation decisions and evaluation of transmission scale. Methods We developed an epidemiological model to describe the prevalence of the mpox virus in New York City and calibrated the model to match surveillance data from May 19 to November 3, 2022. Finally, we adjusted the model to simulate and compare several scenarios of non-vaccination and pre-pandemic vaccination. Results Relative to the status quo, if vaccination is not carried out, the number of new infections increases to about 385%, and the transmission time will be extended to about 350%, while if vaccinated before the epidemic, the number of new infections decreases to 94.2-96%. Conclusions The mpox outbreak in New York City may be linked to the Pride event. However, with current vaccine coverage, there will be no more large-scale outbreaks of mpox, even if there is another similar activity. For areas with limited vaccines, priority is given to high-risk groups in the age group [34–45] years as soon as possible. …

Abstract Background Viral neutralization (NT) assays can be used to determine the immune status of patients or assess the potency of candidate vaccines or therapeutic monoclonal antibodies (mAbs). Focus reduction neutralization test (FRNT) is a conventional neutralization test (cVNT) with superior specificity for measurement of neutralizing antibodies against a specific virus. Unfortunately, the application of FRNT to the chikungunya virus (CHIKV) involves a highly pathogenic bio-agent requiring biosafety level 3 (BSL3) facilities, which inevitably imposes high costs and limits accessibility. In this study, we evaluated a safe surrogate virus neutralization test (sVNT) that uses novel CHIKV replicon particles (VRPs) expressing eGFP and luciferase (Luc) to enable the rapid detection and quantification of neutralizing activity in clinical human serum samples. Methods This unmatched case-control validation study used serum samples from laboratory-confirmed cases of CHIKV (n = 19), dengue virus (DENV; n = 9), Japanese encephalitis virus (JEV; n = 5), and normal individuals (n = 20). We evaluated the effectiveness of sVNT, based on mosquito cell-derived CHIK VRPs (mos-CHIK VRPs), in detecting (eGFP) and quantifying (Luc) neutralizing activity, considering specificity, sensitivity, and reproducibility. We conducted correlation analysis between the proposed rapid method (20 h) versus FRNT assay (72 h). We also investigated the correlation between sVNT and FRNT in NT titrations in terms of Pearson’s correlation coefficient (r) and sigmoidal curve fitting. Results In NT screening assays, sVNT-eGFP screening achieved sensitivity and specificity of 100%. In quantitative neutralization assays, we observed a Pearson’s correlation coefficient of 0.83 for NT50 values between sVNT-Luc and FRNT. Conclusions Facile VRP-based sVNT within 24 h proved highly reliable in the identification and quantification of neutralizing activity against CHIKV in clinical serum samples. …

Abstract Background After recovering from the acute phase of COVID-19, some of the infected children manifest long COVID symptoms. The present study aims to identify long COVID symptoms in children and adolescents admitted to hospitals in Bushehr, Iran, during 2021 to 2023, and compare them with the non-affected group. Methods This historical cohort study with a population-based control group was conducted on 141 children and adolescents with COVID-19 hospitalized in Bushehr city hospitals and 141 non-affected peers. Out of 10 comprehensive health service centers in Bushehr city, 5 centers were selected by random sampling and the non-Covid-19 group was chosen from them (matched by gender and age with the affected group). The data were collected using the data recorded in the patients’ records, conducting telephone interviews and completing the prevalent long COVID symptom form. Data were analyzed using SPSS version 18. Descriptive statistics, Chi-square/Fisher’s exact tests, and stepwise logistic regression were used. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with p 

Abstract Background Pulmonary nocardiosis (PN) is a rare and opportunistic infection. This study aimed to analyze clinical, radiological, and microbiological features, treatment and outcome of PN in southern china. Methods Clinical, laboratory, imaging, treatment and outcome data of PN patients at two tertiary hospitals from January 1, 2018, to January 1, 2024 were collected. Factors associated with clinical outcomes were determined by multivariate logistic regression analysis. Results 67 PN patients including 53 with clinical improvement and 14 with treatment failure were enrolled. Bronchiectasis was the most common respiratory disease in patients with PN (31.3%). The major symptoms of PN were cough (89.6%) and sputum (79.1%). Lung nodules, bronchiectasis, consolidation, pleural involvement, mass, cavity, and lymph node enlargement were the frequent computed tomography findings of PN. Among the Nocardia species detected, N. farcinica was the most common pathogen. Neutrophil-to-lymphocyte ratio (OR = 1.052, p = 0.010), concurrent bacterial infection (OR = 7.706, p = 0.016), and the use of carbapenems (OR = 9.345, p = 0.023) were independently associated with poor prognosis in patients with PN. Conclusions This study provides important insights into the clinical features of PN in southern china. neutrophil-to-lymphocyte ratio, concurrent bacterial infection, and the use of carbapenems were independently associated with poor prognosis in patients with PN. …

Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal.

Abstract For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

by Antoine Froment, Julia Delomez, Sophie Da Nascimento, Alexandra Dassonville-Klimpt, Claire Andréjak, François Peltier, Cédric Joseph, Pascal Sonnet, Jean-Philippe Lanoix The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo, in a mouse model of M. avium intraveinous infection. However, no study reports aerosol model of infection or combination with gold standard treatment. That was the aim of our study. In an aerosol model of M. avium infection in BALB/c mice, we used five treatment groups as followed: Clarithromycin-Ethambutol-Rifampicin (CLR-EMB-RIF, standard of care, n = 15), CLR-EMB-MFQ (n = 15), CLR-EMB-(+)-EMQ (n = 15), CLR-EMB-(-)-EMQ (n = 15) and an untreated group (n = 25). To evaluate drug efficacy, we sacrificed each month over 3 months, 5 mice from each group. Lung homogenates were diluted and plated for colony forming unit count (CFU) expressed in Log10. At each time point, we found a significant difference between the untreated group and each of the treatment groups (p…

by Xia Wu, Jinjun Cai, Zhangjun Wang, Weiqian Li, Gang Chen, Yangyang Bai The bacterial community performs an essential ecological role in maintaining agriculture systems. The roles of bacteria in the forest, marine, and agricultural systems have been studied extensively and intensively. However, similar studies in the areas irrigated by the Yellow River remain limited. In this study, we used Illumina sequencing analysis with the 16S rRNA method to analyze the bacterial diversity, community structure, and influencing factors in soil samples from eight regions of the Yellow River irrigation area in northwestern China. The bacterial community structure and diversity varied among samples from the eight regions. The samples differed significantly in terms of the bacterial community composition. Proteobacteria (approximately 12.4%-55.7%) accounted for the largest proportion and was the dominant bacteria, followed by Actinobacteria (approximately 9.2%-39.7%), Bacteroidetes (approximately 1.8%-21.5%), and Chloroflexi (approximately 2.7%-12.6%). Among the physicochemical variables, the soil pH in the eight regions was mildly alkaline, and the total nitrogen, total phosphorus, and total potassium contents in the soils differed significantly. However, the trend in the variations of the above variables was essentially similar. Soil bacteria in Yongning county had greater Chao1, Shannon-Wiener, and Simpson indices than those in the other regions. Notably, soil moisture, organic matter, and total nitrogen were recognized as the primary factors influencing the bacterial community in the Yellow River irrigation area. Our results revealed the laws of variation in soil bacterial diversity and community composition in the Yellow River irrigation area. Our findings could be beneficial for maintaining sustainable ecological practices in the Yellow River irrigation area.

by Louise S. Cox, Mark Naunton, Gregory M. Peterson, Nasser Bagheri, Jake Paul Bennetts, Jane Koerner, Rachel Davey, Sam Kosari Older people in residential aged care are susceptible to acute illness or injury which may necessitate an ambulance call out, assessment/treatment by a paramedic and transfer to a hospital emergency department. Understanding the case mix of residential aged care ambulance attendances is important for prevention strategies and for planning services. A retrospective observational closed cohort study was designed to investigate the characteristics of emergency ambulance call outs to 15 residential aged care sites in the Australian Capital Territory over a 12-month period. Data were collected from the local ambulance service and the aged care sites. Case load data were analysed to determine rates, clinical characteristics, ambulance attendance outcomes and the temporal distribution of call outs. A Poisson regression model was developed to investigate demographic, morbidity and medication-related risk factors associated with the number of ambulance call outs per resident. Annual ambulance call out costs were estimated. There were 1,275 residents, with 396 (31.1%) requiring at least one ambulance call out over 12 months. Of 669 ambulance attendances, the majority (87.0%) were transported to emergency departments. Trauma (23.9%), pain (16.9%) and infections (9.4%) were the most common primary assessments by the ambulance attendees. Cases/day were similar throughout the year and on weekdays compared to weekends/public holidays. The main predictors of ambulance call out were multi-morbidity, taking regular anticholinergic medicines, being male and younger age. Estimated costs of ambulance call outs/year were $475/resident and $40,375/residential aged care site. The most frequent primary assessments (trauma, pain, infections) may constitute priorities for developing prevention strategies and for treatment initiatives within residential aged care. Strategies to reduce anticholinergic medication prescribing may also be a potential intervention to decrease ambulance call outs and hospital emergency department demand. The ambulance usage data from this study may be useful to compare with future datasets to measure the impact of the introduction of new services.

by Zeynab Hosseinpoor, Zahra-Soheila Soheili, Maliheh Davari, Hamid Latifi-Navid, Shahram Samiee, Dorsa Samiee Regulation of visual system function demands precise gene regulation. Dysregulation of miRNAs, as key regulators of gene expression in retinal cells, contributes to different eye disorders such as diabetic retinopathy (DR), macular edema, and glaucoma. MIR-96, a member of the MIR-183 cluster family, is widely expressed in the retina, and its alteration is associated with neovascular eye diseases. MIR-96 regulates protein cascades in inflammatory and insulin signaling pathways, but further investigation is required to understand its potential effects on related genes. For this purpose, we identified a series of key target genes for MIR-96 based on gene and protein interaction networks and utilized text-mining resources. To examine the MIR-96 impact on candidate gene expression, we overexpressed MIR-96 via adeno-associated virus (AAV)-based plasmids in human retinal pigment epithelial (RPE) cells. Based on Real-Time PCR results, the relative expression of the selected genes responded differently to overexpressed MIR-96. While the expression levels of IRS2, FOXO1, and ERK2 (MAPK1) were significantly decreased, the SERPINF1 gene exhibited high expression simultaneously. pAAV-delivered MIR-96 had no adverse effect on the viability of human RPE cells. The data showed that changes in insulin receptor substrate-2 (IRS2) expression play a role in disrupted retinal insulin signaling and contribute to the development of diabetic complications. Considered collectively, our findings suggest that altered MIR-96 and its impact on IRS/PI3K/AKT/VEGF axis regulation contribute to DR progression. Therefore, further investigation of the IRS/PI3K/AKT/VEGF axis is recommended as a potential target for DR treatment.

by Chu-Yun Liu, Yu-Shen Yang, Meng-Qin Pei, He-fan He The objective of this study was to explore the potential causalities of fat mass, nonfat mass and height (henceforth, ‘anthropometric measures’) with sepsis risk and mortality. We conducted the Mendelian randomization (MR) investigation using genome-wide association study (GWAS) summary statistics of anthropometric measures, sepsis, and sepsis mortality. The GWAS summary data from the UK Biobank was used. Firstly, MR analysis was performed to estimate the causal effect of anthropometric measures on the risk of sepsis. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach, together with weighted median-based method. Cochrane’s Q test and MR-Egger intercept test were performed to assess heterogeneity and pleiotropy, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted weight-related measures were suggestively linked to an increased risk of sepsis. However, height displayed no causal association with sepsis risk and mortality. Furthermore, weight-related measures also displayed significant MR association with the sepsis mortality, except body nonfat mass and right leg nonfat mass. However, MVMR analysis indicated the observed effects for weight-related measures in the univariable MR analyses are more likely a bias caused by the interrelationship between anthropometric measures. According to the MR-Egger intercept assessment, our MR examination was not influenced by horizontal pleiotropy (all p>0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. In conclusion, these findings provided vital new knowledge on the role of anthropometric-related measures in the sepsis etiology.

by Awad M. Almuklass, Abdulmajeed Mansour Alassaf, Rakan F. Alanazi, Turki Rashed Alnafisah, Thamir Ali Alrehaily, Yaser Al Malik Introduction The median and ulnar nerves have been suggested to play a significant role in hand function; however, there are insufficient data to determine the strength of this association. This study aimed to investigate the correlation between hand function as measured with the Grooved pegboard test (GPT) and conduction velocity and latency of the median and ulnar nerves. Methods We collected convenience samples in the College of Medicine, KSAU-HS. We used GPT to characterize hand function and performed measured nerve conduction velocity (NCV) and latency of the ulnar and median nerves of both hands. We used the Edinburgh handedness inventory (EHI) to determine hand dominance. Results We recruited 28 healthy medical students aged 20–29 years (mean: 21.46 ± 1.62 years). Most were right-handed (n = 25, 89.3%), with a mean EHI score of 302 ± 210. The mean GPT time was significantly faster in the dominant (65.5 ± 6.4 s) than in the non-dominant (75.0 ± 9.6 s) hand. The NCV for the ulnar nerve of the dominant hand was significantly correlated with GPT (r = -0.52, p = 0.005) while median nerve was not correlated (0.24, p = 0.21). Regression analysis and collinearity test showed that the ulnar NCV explained 20% of the variance in GPT of the dominant hand (R2 = 0.203, p = 0.016). Conclusion The ulnar nerve conduction velocity, explained 20% of the variance in GPT times of the young men. Performance on this biomarker of neurological health seems to be more influenced by other factors in healthy young individuals. …