bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 in patients with chronic kidney disease: a 2-year study of incidence and mortality in relation to the variants of concern waves in Brazil
Authors: Almeida Nathalie Bonatti Franco , Filgueiras Priscilla Soares , Lourenço Adelina Junia , Bicalho Cecilia Maria Florencio , Corsini Camila Amormino , de Miranda Daniel Alvim Pena , Gomes Sarah Vieira Contin , Vilela Raquel V R , Grenfell Rafaella Fortini Queiroz
Published: April 2023

Background

Chronic kidney disease (CKD) is a risk factor for severe coronavirus disease (COVID-19). In Brazil, the disease is the 10th highest cause of death. We evaluated the epidemiological impact of COVID-19 in CDK and non-CDK patients.

Methods

Positive patients for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2020 to 2022 were classified according to the severity of COVID-19 and the numbers of cases and deaths were correlated to each wave of SARS-CoV-2 variants in Brazil.

Results

We compared all variables, and our data show that CDK significantly increased the mortality rate among patients, especially before COVID-19 vaccination, in comparison with non-CKD patients.

Conclusions

CKD patients had a significantly increased mortality rate compared with non-CKD.
A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya
Authors: Joekes Elizabeth , McMonnies Kate , Blanshard Andrew , Mutuku Francis M , Ireri Edmund , Mungai Peter , Stothard J Russell , Bustinduy Amaya L , King Charles H
Published: April 2023

Background

Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied.

Methods

Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000.

Results

Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality.

Conclusions

Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.
Ferroptosis of brain microvascular endothelial cells contributes to hypoxia‐induced blood–brain barrier injury
Authors: Liu Qiuling , Song Tujing , Chen Bing , Zhang Jingjing , Li Wen
Published: April 2023

Hypoxia is pivotal to the pathogeneses of myriad disorders, especially hypoxic cerebropathy. Much is known about the damage to the blood–brain barrier (BBB) in response to hypoxia. Studies have shown that endothelial cell death is closely linked to functional impairment of BBB. Mounting evidences have demonstrated that ferroptosis, a new pathway regulating cell death, is implicated in brain injury. However, whether ferroptosis is involved in hypoxia‐induced BBB disruption remains ambiguous. Here, we utilized in vivo zebrafish and in vitro bEnd.3 cells to explore the correlation between endothelial ferroptosis and hypoxia‐induced BBB damage. We found that hypoxic treatment for 45 min can induce BBB disruption by triggering down‐regulation of claudin‐5 (CLDN5) both in zebrafish cerebrovascluar endothelial cells and bEnd.3 cells. Besides, in vitro and in vivo studies revealed the cysteine/glutamate antiporter xCT (also known as solute carrier family 7 member 11; SLC7A11) decrease, glutathione peroxidase 4 (GPX4) and glutathione (GSH) reduction, 4‐Hydroxynonenal (4‐HNE) increasement, malondialdehyde (MDA) upregulation and reactive oxygen species (ROS) accumulation in hypoxia group. Further mechanism studies indicated that hypoxia‐induced BBB damage might associate with microvascular endothelial cellular ferroptosis, since hypoxic exposure significantly activated the expression of ferroptosis‐related genes (Ptgs2, Por, Lpcat3, Alox5, Alox12, Nfe2l2, and Ncoa4) and inhibited the expression of Slc7a11. Additionally, the application of 20 μM ferrostatin‐1 (Fer‐1), a ferroptosis inhibitor, could partially alleviate BBB disruption under hypoxia, suggesting that inhibition of ferroptosis might be a potential strategy for some neurological diseases with BBB defect.
Diagnosing and managing adrenal incidentalomas
Authors: Herndon Justine , Bancos Irina
Published: April 2023

Adrenal incidentalomas are commonly encountered because of the widespread use of high-resolution cross-sectional imaging. Adrenal incidentalomas may be benign or malignant, and also may demonstrate hormonal hypersecretion, so all patients with adrenal masses should undergo further assessment. Clinicians should have a basic understanding of adrenal incidentalomas, their workup, and when follow-up and referral are warranted.
Complexity in Epidemiology and Public Health. Addressing Complex Health Problems Through a Mix of Epidemiologic Methods and Data
Authors: Rod Naja Hulvej , Broadbent Alex , Rod Morten Hulvej , Russo Federica , Arah Onyebuchi A. , Stronks Karien
Published: April 2023

Public health and the underlying disease processes are complex, often involving the interaction of biologic, social, psychologic, economic, and other processes that may be nonlinear and adaptive and have other features of complex systems. There is therefore a need to push the boundaries of public health beyond single-factor data analysis and expand the capacity of research methodology to tackle real-world complexities. This article sets out a way to operationalize complex systems thinking in public health, with a particular focus on how epidemiologic methods and data can contribute towards this end. Our proposed framework comprises three core dimensions—patterns, mechanisms, and dynamics—along which complex systems may be conceptualized. These dimensions cover seven key features of complex systems—emergence, interactions, nonlinearity, interference, feedback loops, adaptation, and evolution. We relate this framework to examples of methods and data traditionally used in epidemiology. We conclude that systematic production of knowledge on complex health issues may benefit from: formulation of research questions and programs in terms of the core dimensions we identify, as a comprehensive way to capture crucial features of complex systems; integration of traditional epidemiologic methods with systems methodology such as computational simulation modeling; interdisciplinary work; and continued investment in a wide range of data types. We believe that the proposed framework can support the systematic production of knowledge on complex health problems, with the use of epidemiology and other disciplines. This will help us understand emergent health phenomena, identify vulnerable population groups, and detect leverage points for promoting public health.
Rapidly Rising Diabetes and Increasing Body Weight: A Counterfactual Analysis in Repeated Cross-sectional Nationally Representative Data from Bangladesh
Authors: Wetzel Sarah , Sarker Malabika , Hasan Mehedi , Talukder Animesh , Sudharsanan Nikkil , Geldsetzer Pascal
Published: April 2023

Background:

Diabetes is a growing concern in South Asia but few nationally representative studies identify factors behind this rising disease burden. We studied the nationwide change in diabetes prevalence in Bangladesh, subpopulations disproportionately affected, and the contribution of rising unhealthy weight to the change in diabetes prevalence.

Methods:

Based on a sample of 13,959 adults aged 35 years and older with biomarker measurements from the 2011 and 2017/2018 Bangladesh Demographic and Health Surveys, we estimated how the prevalence of diabetes changed nationally and across socioeconomic/geographic groups. Using counterfactual decomposition, we assessed how much the prevalence of diabetes would have grown if body mass index (BMI) had not changed between 2011 and 2017.

Results:

Diabetes prevalence increased from 12.1% (11.1, 13.1) to 14.4% (13.3, 15.5) between 2011 and 2017/2018. Diabetes grew disproportionately quickly among population groups with higher household wealth, and more education, and in three regions. Over this same period, mean BMI increased from 20.9 (20.8, 21.1) to 22.5 kg/m2 (22.4, 22.7) and overweight from 25.8 (24.4, 27.3) to 42.1% (40.4, 43.7). Under the counterfactual scenario of constant BMI, diabetes would have risen by only 1.0 (−0.4, 2.4) instead of 2.3 percentage points (0.8, 3.7) nationally, corresponding to a contribution of 58% (−106.3, 221.7). Similarly, group-specific trends were largely attributable to increasing BMI.

Conclusions:

Diabetes prevalence in Bangladesh has increased rapidly between 2011 and 2017/2018. Decomposition analysis estimates have wide confidence intervals but are consistent with the hypothesis that this change was driven by the dramatic rise in body weights.
Clinical Characteristics and Chinese Medicine Therapy of Chronic Kidney Disease Combined with Cardiovascular Disease
Authors: Zhu Tingting , Du Yating , Xuan Mingyang , Guo Chuan , Rao Xiangrong
Published: April 2023

Chronic kidney disease (CKD) is a serious public health concern worldwide. Cardiovascular disease (CVD) is the leading cause of death in CKD patients. CKD combined with CVD (CKD-CVD) is a common disease with a poor prognosis. Modern medicine for the treatment of CKD-CVD currently focuses on controlling the traditional risk factors of CVD. However, its efficacy is lower than expected, and revascularization shows no notable benefit to patients. The reason for this unsatisfactory clinical outcome is that CKD-CVD has a specific pathophysiological mechanism and atypical clinical presentation. Due to the inadequacy of the therapeutic effects of modern medicine, Chinese medicine (CM) is recommended to delay disease progression. CM is widely used to treat CKD. Furthermore, some theoretical and clinical explorations on the CM treatments of CKD-CVD have been undertaken in recent years. However, clinical trials on the long-term effects of CM on cardiovascular outcomes in patients with CKD is lacking, especially studies on combined cardiac and renal endpoints. This article summarises the clinical characteristics and main treatments of CKD-CVD. Besides, based on CM theory, it is proposed that a deficiency of the spleen and kidney Qi, water dampness, dampness turbidity, and blood stasis contribute to the pathogenesis of CKD-CVD, treatment should focus on tonifying the spleen and kidney Qi, supplemented by smoothing the triple energizer, detoxification, and activation of blood circulation. In order to provide some reference for the combined treatment of Chinese and Western medicine for CKD-CVD.
The comparison of efficacy and safety evaluation of vacuum-assisted Elite 10-G system and the traditional BARD 14-G core needle in breast diagnosis: an open-label, parallel, randomized controlled trial
Authors: Zhang Ying , Li Junjie , Mo Miao , Shen Juping , Ren Hui , Li Shiping , Liu Guangyu , Shao Zhimin
Published: April 2023

Background:

Vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) are both widely used methods in diagnosing breast lesions. We aimed to determine whether the Elite 10-gauge VAB achieves higher accuracy than the BARD spring-actuated 14-gauge CNB.

Materials and methods:

This was a phase 3, open-label, parallel, randomized controlled trial (NCT04612439). In total, 1470 patients with ultrasound (US)-visible breast lesions requiring breast biopsy were enrolled from April to July 2021 and randomized at a 1 : 1 ratio to undergo VAB or CNB. All patients underwent surgical excision after needle biopsy. The primary outcome was accuracy, defined as the proportion of patients who had a consistent qualitative diagnosis between the biopsy and surgical pathology results. The underestimation rate, false-negative rate and safety evaluations were the secondary endpoints.

Results:

A total of 730 and 732 patients were evaluable for endpoints in the VAB and CNB groups, respectively. The accuracy of VAB surpassed that of CNB in the whole population (94.8 vs. 91.1%, P=0.009). The overall malignant underestimation rate was significantly lower in the VAB group than in the CNB group (21.4 vs. 30.9%, P=0.035). Additionally, significantly more false-negative events were noted in the CNB group (4.9 vs. 7.8%, P=0.037). In patients who presented with accompanying calcification, the accuracy of VAB surpassed that of CNB (93.2 vs. 88.3%, P=0.022). The potential superiority of VAB was indicated in patients with heterogeneous echo on US.

Conclusions:

In general, the 10-G VAB procedure is a reasonable alternative to the 14-G CNB procedure with higher accuracy. We recommend the use of VAB for lesions with accompanying calcification or heterogeneous echo on US.
The AFLETES Study: Atrial Fibrillation in Veteran Athletes and the Risk of Stroke
Authors: Pallikadavath Susil , Richards Caryl , Bountziouka Vasiliki , Sandilands Alastair J. , Graham-Brown Matthew P. M. , Robinson Thompson , Singh Anvesha , McCann Gerry P.
Published: April 2023

Objectives:

Endurance athletes are at an increased risk of atrial fibrillation (AF) when compared with the general population. However, the risk of stroke in athletes with AF is unknown.

Design and Setting:

We aimed to assess this risk using an international online survey.

Patients:

Individuals that had competed in ≥1 competitive events and were ≥40 years old were included.

Interventions:

Self-reported demographic, medical history, and training history data were collected, and a CHA2DS2-VASc was calculated.

Main Outcome Measures:

Binary logistic regression was used to assess variables associated with AF and stroke.

Results:

There were 1002 responses from participants in 41 countries across Africa, Asia, Australasia, Europe, and North and South America, and 942 were included in the final analysis. The average age was 52.4 ± 8.5 years, and 84% were male. The most common sports were cycling (n = 677, 72%), running (n = 558, 59%), and triathlon (n = 245, 26%). There were 190 (20%) individuals who reported AF and 26 individuals (3%) who reported stroke; of which, 14 (54%) had AF. Lifetime exercise dose [odds ratio (OR), 1.02, 95% confidence interval (95% CI),1.00-1.03, P = 0.02] and swimming (OR, 1.56, 95% CI, 1.02-2.39, P = 0.04) were associated with AF in multivariable analysis, independent of other risk factors. Atrial fibrillation was associated with stroke (OR, 4.18, 95% CI, 1.80-9.72, P < 0.01), even in individuals with a low (0/1) CHA2DS2-VASc score (OR, 4.20, 95% CI, 1.83-9.66, P < 0.01).

Conclusions:

This survey provides early evidence that veteran endurance athletes who develop AF may be at an increased risk of developing stroke, even in those deemed to be at low risk by CHA2DS2-VASc score.
Uterine MEIS1::NCOA2 Fusion Sarcoma With Lung Metastasis: A Case Report and Review of the Literature
Authors: Xing Deyin , Meyer Christian F. , Gross John M. , Argani Pedram , Hung Chien-Fu , Wu T.-C. , Vang Russell , Armstrong Deborah K. , Gaillard Stéphanie L.
Published: April 2023

MEIS1::NCOA1/2 fusion sarcomas are a recently described novel entity arising in a variety of locations with a predilection for the genitourinary tract and gynecologic organs. Despite multiple locoregional recurrences, these tumors are thought to behave in a low-grade malignant manner. Here we report a uterine MEIS1::NCOA2 fusion sarcoma with lung metastasis. The patient was a 47-yr-old woman with a history of abnormal uterine bleeding who was found to have a myometrial mass confirmed by pathology to be uterine sarcoma. The tumor was predominantly composed of monotonous spindle cells with scant cytoplasm, crowded nuclei, and brisk mitotic activity, growing in a fascicular and streaming pattern. The morphologic and immunophenotypic features were nonspecific and a diagnosis of high-grade uterine sarcoma with a differential of leiomyosarcoma versus high-grade endometrial stromal sarcoma was rendered. At the 27-mo follow-up, the patient was found to have a lung metastasis consisting of a monotonous round cell sarcoma. A retrospective RNA-based and DNA-based next-generation sequencing of the primary uterine sarcoma revealed a MEIS1::NCOA2 gene fusion, a c.94G>C/p.D32H mutation in exon 3 of CTNNB1 gene, HMGA2, and CDK4 gene amplification, and an intermediate/marginal level of MDM2 gene amplification. Polymerase chain reaction–based molecular analysis further demonstrated that the MEIS1::NCOA2 gene fusion and CTNNB1 somatic mutation were also present in the lung metastasis. This case represents the first case of such gynecologic sarcoma with distant (lung) metastasis, and the second metastatic case among all reported MEIS1::NCOA1/2 fusion sarcomas, highlighting the malignant metastatic potential of this emerging entity. Our case also indicates that HMGA2/CDK4/MDM2 region amplification and CTNNB1 somatic mutation might be recurrent genetic events in this rare sarcoma subtype.
Audio Care for Managing Diabetes: A Rapid Review
Authors: Reddy Shivani M. , Kugley Shannon , Booth Graham , Dalton Jennie , Rodriguez Borja Ivette , Coker-Schwimmer Manny , Patel Sheila V. , Bonds Denise , Prum Soknorntha , Fujita Miku , Philbrick Sarah , Ruwala Richa , Albritton Jordan A. , Crotty Karen
Published: April 2023

  

We compared the effectiveness of audio care, as a replacement or a supplement to usual care, for managing diabetes.
Biocontrol of snail-borne parasites with the glossiphoniid leech,
Helobdella austinensis
Authors: Saglam Naim , Melissaratos Diana S. , Shain Daniel H.
Published: April 2023

Parasites in which freshwater snails are intermediate hosts pose a serious threat to human health worldwide. We show here that freshwater snails can potentially be controlled by leech predation; in principle, this approach could significantly reduce snail-borne parasitic diseases (SBPDs). Specifically, glossiphoniid leeches,
Helobdella austinensis
and congener species
,
consume freshwater snails indiscriminately, while other common leeches do not. A single adult
H. austenensis
, for example, can consume up to its weight in snails, e.g.
Physella acuta,
per day. Our predator–prey models suggest that snail populations could be eliminated in relatively short time periods (approximately six months) using a leech biocontrol approach. This could have considerable impact on global SBPDs by breaking the intermediate host life cycle.
Structure and mechanics of water-holding feathers of Namaqua sandgrouse (
Pterocles namaqua
)
Authors: Mueller J. , Gibson L. J.
Published: April 2023

Desert sandgrouse, such as the Namaqua sandgrouse, nest up to 30 km away from watering holes. Adult male desert sandgrouse have specially adapted feathers on their bellies that hold water, even during flight, allowing the birds to transport water back to the chicks at the nest. The structure of the belly feathers and aspects of the mechanism by which they hold water was first described by Cade and Maclean (Cade, Maclean 1967
Condor
69
, 323–343 (
doi:10.2307/1366197
)). Here, we use scanning electron microscopy and micro-computed tomography as well as videography to characterize the geometry of different components of the belly feathers and to show how differences in their bending stiffnesses contribute to the water-holding mechanism. The results of this study will be used in a companion paper to model computationally water uptake by the feather.
The historical power of the natural science collection of Dominik Bilimek at the University of Natural Resources and Life Sciences Vienna (BOKU)
Authors: Lukeneder Petra , Liebhart Irene , Ottner Franz , Mikes Anika , Heinz Petra , Polách Radek
Published: April 2023

The scientific world of the nineteenth century was shaped by far-reaching discoveries, expeditions, travel and collection activities as well as by the development of extensive natural scientific social networking. During the 1840s, Dominik Bilimek (1813–1884) arose as a key personality in European natural sciences, with a significant impact on the biological, geoscientific and even archaeological communities. The Bilimek collection at the University of Natural Resources and Life Sciences Vienna encompasses thousands of specimens and provides a large number of original labels with date, locality and companions in the field. This set of collection labels was analysed qualitatively and quantitatively with respect to its historical value to increase our knowledge about the explorer's life and his social network. The study also focuses on Bilimek's so far unknown social links, which were recovered by the processing of the collection, probably resulting in the use of these data for a social network analysis of a nineteenth-century scientific network.
A multiphasic approach to solve misidentification of Cutibacterium acnes as Atopobium vaginae during routine bacterial screening of platelet concentrates using the VITEK 2 system
Authors: Kumaran Dilini , Laflamme Carmelie , Ramirez-Arcos Sandra
Published: April 2023

Skin flora bacteria, such as Cutibacterium acnes, are the predominant contaminants of blood products used for transfusion. Platelet concentrates (PCs), a therapeutic product used to treat patients with platelet deficiencies, are stored at ambient temperature under agitation, providing ideal conditions for bacterial proliferation. PCs are screened for microbial contamination using the automated BACT/ALERT culture system. Positive cultures are processed and contaminating organisms are identified using the VITEK 2 system. Over a period of approximately 2 years, several PC isolates were identified as Atopobium vaginae to a high level of confidence. However, since A. vaginae is associated with bacterial vaginosis and is not a common PC contaminant, a retrospective investigation revealed that in all cases C. acnes was misidentified as A. vaginae. Our investigation demonstrated that the media type used to grow PC bacterial isolates can have a significant impact on the results obtained on the VITEK 2 system. Furthermore, other identification methods such as MALD-ToF and PCR amplification of the 16s RNA gene were only partially successful in the identification of C. acnes. Therefore, our findings support a multiphasic approach when PC isolates are identified as A. vaginae by the VITEK 2 system for proper identification of C. acnes using macroscopic, microscopic, and other biochemical analyses.
Replication and innate immune responses of two chikungunya virus genotypes in human monocyte-derived macrophages
Authors: Lau Joanne Zhi Han , Chua Chong Long , Chan Yoke Fun , Nadarajan Veera Sekaran , Lee Christina Lai Ling , Sam I-Ching
Published: April 2023

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs. In vivo, this may lead to poorer initial control of viral infection, facilitating CHIKV replication and dissemination to other sites such as joints. This may explain the consistent past findings that the ECSA genotype is associated with greater viremia and severity of symptoms than the Asian genotype. Knowledge of CHIKV genotype-specific immunopathogenic mechanisms in human MDMs is important in understanding of clinical epidemiology, biomarkers and therapeutics in areas with co-circulation of different genotypes.
Comparing genomic variant identification protocols for Candida auris
Authors: Li Xiao , Muñoz José F. , Gade Lalitha , Argimon Silvia , Bougnoux Marie-Elisabeth , Bowers Jolene R. , Chow Nancy A. , Cuesta Isabel , Farrer Rhys A. , Maufrais Corinne , Monroy-Nieto Juan , Pradhan Dibyabhaba , Uehling Jessie , Vu Duong , Yeats Corin A. , Aanensen David M. , d’Enfert Christophe , Engelthaler David M. , Eyre David W. , Fisher Matthew C. , Hagen Ferry , Meyer Wieland , Singh Gagandeep , Alastruey-Izquierdo Ana , Litvintseva Anastasia P. , Cuomo Christina A.
Published: April 2023

Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies.
Vibrio cholerae O37: one of the exceptions that prove the rule
Authors: Dorman Matthew J. , Thomson Nicholas R.
Published: April 2023

Between 1965 and 1968, outbreaks of cholera in Sudan and former Czechoslovakia provoked considerable public health concern. These still represent important historical events that need to be linked to the growing genomic evidence describing the aetiological agent of cholera,

Vibrio cholerae

. Whilst O1 serogroup

V. cholerae

are canonically associated with epidemic and pandemic cholera, these events were caused by a clone of toxigenic

V. cholerae

O37 that may be more globally distributed than just to Europe and North Africa. Understanding the biology of these non-O1 strains of

V. cholerae

is key to understanding how diseases like cholera continue to be globally important. In this article, we consolidate epidemiological, molecular and genomic descriptions of the bacteria responsible for these outbreaks. We attempt to resolve discrepancies in order to summarize the history and provenance of as many commonly used serogroup O37 strains as possible. Finally, we highlight the potential for whole-genome sequencing of

V. cholerae

O37 isolates from strain collections to shed light on the open questions that we identify.
A journey with type IX secretion system effectors: selection, transport, processing and activities
Authors: Paillat Maëlle , Lunar Silva Ignacio , Cascales Eric , Doan Thierry
Published: April 2023

The type IX secretion system (T9SS) is a multiprotein machine distributed in

Bacteroidota

and responsible for the secretion of various proteins across the outer membrane. Secreted effectors can be either delivered into the medium or anchored to the cell surface. The T9SS is composed of a transenvelope complex consisting of proton-motive force-dependent motors connected to a membrane-associated ring and outer membrane translocons, and a cell-surface anchoring complex that processes effectors once translocated. The T9SS is involved in pathogenesis, metal acquisition, carbohydrate degradation, S-layer biogenesis and gliding motility. The broad spectrum of functions is linked to a highly versatile repertoire of effectors including metallophores, enzymes, toxins and adhesins, that all possess specific signatures to be recruited and transported by the apparatus. This review summarizes the current knowledge on T9SS substrate secretion signals, transport, processing and activities.
CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues
Authors: Aguillon Raphael , Rinsky Mieka , Simon-Blecher Noa , Doniger Tirza , Appelbaum Lior , Levy Oren
Published: April 2023

The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL or pacemaker) with CLOCK as a conserved positive factor in animals. However, CLOCK’s functional evolutionary origin and mechanism of action in basal animals are unknown. In the cnidarianNematostella vectensis, pacemaker gene transcript levels, includingNvClk(theClockortholog), appear arrhythmic under constant darkness, questioning the role of NvCLK. Utilizing CRISPR/Cas9, we generated aNvClkallele mutant (NvClkΔ), revealing circadian behavior loss in constant light conditions (LL and DD) while a 24-hour rhythm was maintained under light-dark condition (LD). Transcriptomics showed distinct rhythmic genes in wild-type (WT) genes in LD compared to DD. The LDNvClkΔ/Δshowed comparable numbers of rhythmic genes, but were greatly reduced in DD. Furthermore, the LDNvClkΔ/Δshowed alterations in temporal pacemaker gene expression, affecting their potential interactions. Additionally, differential expression of non-rhythmic genes associated with cell division and neuronal differentiation was observed. These findings revealed that a light-responsive pathway can partially compensate for circadian clock disruption and that theClockgene has evolved in cnidarians to synchronize rhythmic physiology and behavior to the diel rhythm of the earth’s biosphere.
Quantification of amyloid protein enrichment by mass spectrometry improves amyloidosis typing
Authors: Di Tommaso Sylvaine , Chauveau Bertrand , Dourthe Cyril , Dupuy Jean-William , Saltel Frédéric , Le Bail Brigitte , Raymond Anne-Aurélie
Published: April 2023

Introduction

Amyloidosis typing is crucial to determine the best therapeutic strategy for patients. Since conventional histological techniques often fail, the identification of amyloid precursors by mass spectrometry became the new standard. However, without quantification, selecting the amyloid precursor from proteins that may be ubiquitous under non-pathological conditions may be equivocal. Therefore, we quantified protein enrichment in amyloid deposits to improve typing.

Methods

Protein enrichment was measured by extracted ion chromatogram based label free quantification by comparing a microdissected amyloid area with a non-amyloid area. We assessed the discrimination ability of candidate precursors with this approach compared to the two practiced identification methods.

Results

As proof of concept, we selected seven cases, 5 typical of the most common amyloidosis subtypes and typed by immunostainings, 2 inconclusive after immunohistochemistry. Proteins associated with amyloid deposits were identified in all samples confirming the pathology. When the routine clinical mass spectrometric identification techniques allowed unambiguous conclusions for 2/3 of 7 cases, quantification of the enrichment ratio in the amyloid deposit allowed unambiguous precursor selection in all cases.

Conclusion

Quantification of precursor enrichment in amyloid deposits is a promising optimization for amyloidosis typing. Incorporated into routine clinical processes, it will improve patient care in difficult diagnostic situations.
Large-scale Integrative Analysis of Juvenile Idiopathic Arthritis for New Insight into Its Pathogenesis
Authors: Kim Daeun , Song Jaeseung , Mancuso Nicholas , Mangul Serghei , Ahn Chul Woo , Jung Junghyun , Jang Wonhee
Published: April 2023

Objectives

Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear. We conducted a comprehensive integrative analysis to gain new insights into the etiology of JIA.

Methods

To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS). Then, to understand genetic architecture JIA, we systematically analyzed single nucleotide polymorphism (SNP)-based heritability, a signature of natural selection, and polygenicity. Finally, we performed HLA typing using multi-ancestry RNA sequencing data and analyzed the T cell receptor (TCR) repertoire at a single-cell level to investigate the associations between immunity and JIA risk.

Results

We have identified 19 TWAS genes and two PWAS proteins that are associated with JIA risks. Furthermore, we observe that the heritability and cell type enrichment analysis of JIA are enriched in T lymphocytes and HLA regions, and that JIA shows higher polygenicity compared to other AIDs. In multi-ancestry HLA typing, B*45:01 is more prevalent in African JIA patients than in European JIA patients, whereas DQA1*01:01, DQA1*03:01, and DRB1*04:01 exhibit a higher frequency in European JIA patients. Using single-cell immune repertoire analysis, we identify clonally expanded T cell subpopulations in JIA patients, includingCXCL13+BHLHE40+THcells which are significantly associated with JIA risks.

Conclusions

Our findings shed new light on the pathogenesis of JIA and provide a strong foundation for future mechanistic studies aimed at uncovering the molecular drivers of JIA
Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID
Authors: Visvabharathy L , Zhu C , Orban ZS , Yarnoff K , Palacio N , Jimenez M , Lim PH , Penaloza-MacMaster P , Koralnik IJ
Published: April 2023

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown. Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers. In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.
A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples
Authors: Vicco Anna , McCormack Clare , Pedrique Belen , Amuasi John H. , Awuah Anthony Afum-Adjei , Obirikorang Christian , Struck Nicole S. , Lorenz Eva , May Jürgen , Ribeiro Isabela , Malavige Gathsaurie Neelika , Donnelly Christl A. , Dorigatti Ilaria
Published: April 2023

The extent to which dengue virus has been circulating in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection; the force of infection (FOI), which is a fundamental measure of transmission intensity.

In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform a dengue seroprevalence survey which is currently being conducted in Ghana by the Drug for Neglected disease initiative, utilizing samples previously collected for a SARS-CoV-2 serosurvey.

The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.

Author summary

The historical circulation of dengue virus in Africa is still poorly understood, and age-stratified seroprevalence surveys can provide the data to quantify population exposure to dengue and its transmission intensity.

In this work, we developed a simulation-based method that can be used to identify the sample sizes and age-distribution of the samples needed to obtain informative estimates of dengue force of infection from existing blood samples. We apply this method to data obtained from a SARS-CoV-2 serological survey, previously conducted in three cities in Ghana.

The proposed method can be used to design serological surveys for other pathogens when using existing blood samples with accompanying age and location are available.
Metagenomics reveals novel microbial signatures of farm exposures in house dust
Authors: Wang Ziyue , Dalton Kathryn R. , Lee Mikyeong , Parks Christine G. , Beane Freeman Laura E. , Zhu Qiyun , González Antonio , Knight Rob , Zhao Shanshan , Motsinger-Reif Alison A , London Stephanie J.
Published: April 2023

Indoor home dust microbial communities, important contributors to human health outcomes, are shaped by environmental factors, including farm-related exposures. Detection and characterization of microbiota are influenced by sequencing methodology; however, it is unknown if advanced metagenomic whole genome shotgun sequencing (WGS) can detect novel associations between environmental exposures and the indoor built-environment dust microbiome, compared to conventional 16S rRNA amplicon sequencing (16S). This study aimed to better depict indoor dust microbial communities using WGS to investigate novel associations with environmental risk factors from the homes of 781 farmers and farm spouses enrolled in the Agricultural Lung Health Study. We examined various farm-related exposures, including living on a farm, crop versus animal production, and type of animal production, as well as non-farm exposures, including home cleanliness and indoor pets. We assessed the association of the exposures on within-sample alpha diversity and between-sample beta diversity, and the differential abundance of specific microbes by exposure. Results were compared to previous findings using 16S. We found most farm exposures were significantly positively associated with both alpha and beta diversity. Many microbes exhibited differential abundance related to farm exposures, mainly in the phylaActinobacteria, Bacteroidetes, Firmicutes, andProteobacteria. The identification of novel differential taxa associated with farming at the genera level, includingRhodococcus, Bifidobacterium, Corynebacterium, andPseudomonas, was a benefit of WGS compared to 16S. Our findings indicate that characterization of dust microbiota, an important component of the indoor environment relevant to human health, is heavily influenced by sequencing techniques. WGS is a powerful tool to survey the microbial community that provides novel insights on the impact of environmental exposures on indoor dust microbiota, and should be an important consideration in designing future studies in environmental health.
Cortical microstructural associations with CSF amyloid and pTau
Authors: Nir Talia M. , Villalón-Reina Julio E. , Salminen Lauren , Haddad Elizabeth , Zheng Hong , Thomopoulos Sophia I. , Jack Clifford R. , Weiner Michael W. , Thompson Paul M. , Jahanshad Neda ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: April 2023

Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer’s disease (AD) pathology. Few studies have evaluated multi-shell dMRI models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI, in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau181and Aβ1–42burden and regional cortical NODDI and MAP-MRI indices in 46 cognitively unimpaired individuals, 18 with mild cognitive impairment, and two with dementia (mean age: 71.8±6.2 years) from the Alzheimer’s Disease Neuroimaging Initiative. We compared findings to more conventional cortical thickness measures. Lower CSF Aβ1–42and higher pTau181were associated with cortical dMRI measures reflecting less hindered or restricted diffusion and greater diffusivity. Cortical dMRI measures were more widely associated with Aβ1–42than pTau181and better distinguished Aβ+ from Aβ-participants than pTau+/- participants. Conversely, cortical thickness was more tightly linked with pTau181. dMRI associations mediated the relationship between CSF markers and delayed logical memory performance, commonly impaired in early AD. dMRI measures sensitive to early AD pathogenesis and microstructural damage may elucidate mechanisms underlying cognitive decline.
Factors associated with differential seropositivity toLeptospira interrogansandLeptospira kirschneriin a high transmission urban setting for leptospirosis in Brazil
Authors: de Oliveira Daiana , Khalil Hussein , Almerinda G. Palma Fabiana , Santana Roberta , Nery Nivison , Quintero-Vélez Juan C. , Zeppelini Caio Graco , do Sacramento Gielson Almeida , Cruz Jaqueline , Lustosa Ricardo , Ferreira Igor Santana , Carvalho-Pereira Ticiana , Diggle Peter J , Wunder Elsio A. , Ko Albert I. , Lopez Yeimi Alzate , Begon Mike , Reis Mitermayer G. , Costa Federico
Published: April 2023

Background

Leptospirosis is a zoonosis caused by pathogenic species of bacteria belonging to the genusLeptospira. Most studies infer the epidemiological patterns of a single serogroup or aggregate all serogroups to estimate overall seropositivity, thus not exploring the risks of exposure to distinct serogroups. The present study aims to delineate the demographic, socioeconomic and environmental factors associated with seropositivity ofLeptospiraserogroup Icterohaemorraghiae and serogroup Cynopteri in an urban high transmission setting for leptospirosis in Brazil.

Methods/Principal Findings

We performed a cross-sectional serological study in five urban informal communities in the city of Salvador, Brazil. During the years 2018, 2020 2021, we recruited 2.808 residents and collected blood samples for serological analysis using microagglutination assays. We used a mixed-effect multinomial logistic regression model to identify risk factors associated with seropositivity for each serogroup. Seropositivity to Cynopteri increased with age in years (OR 1.03; 95% CI 1.01-1.06) and was higher in those living in houses with unplaster walls (exposed brick) (OR 1.68; 95% CI 1.09-2.59) and where cats were present near the household (OR 2.00; 95% CI 1.03-3.88). Seropositivity to Icterohaemorrhagiae also increased with age in years (OR 1.02; 95% CI 1.01-1.03) but was higher in males (OR 1.51; 95% CI 1.09-2.10), in those with work-related exposures (OR 1.71; 95% CI 1.10-2.66) or who had contact with sewage (OR 1.42; 95% CI 1.00-2.03). Spatial analysis showed differences in distribution of seropositivity to serogroups Icterohaemorrhagiae and Cynopteri within the five districts where study communities were situated.

Conclusions/Significance

Our data suggests distinct epidemiological patterns associated with serogroups Icterohaemorrhagiae and Cynopteri within the high-risk urban environment for leptospirosis and with differences of spatial niches. Future studies must identify the different pathogenic serogroups circulating in low-income areas, and further evaluate the potential role of cats in the transmission of the serogroup Cynopteri in urban settings.