bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in Diagnosis of Crimean-Congo Hemorrhagic Fever
Authors: Almayahi Zayid K. , Al Kindi Hanan , Al Jabri Ishaq , Al Shaqsi Nasser , Al Hattali Noaman , Al Hattali Azza , Al Quyoodhi Badriya , Al Dhuhli Khalid 
Published: February 2022

Abstract
Crimean-Congo hemorrhagic fever is a serious and fatal disease. Since the disease was first identified in the first half of the last century, it has caused hundreds of fatalities worldwide. Although it is believed that the prognosis for each patient increases with early detection and management, some patients present in the late stage, whereas others may not be detected at all. The risk of disease transmission has increased in many countries in the Middle East, Eastern Europe, and Africa for many reasons, especially the existing challenges of the surveillance and control in the human and animal population, the limited testing and diagnostic capacity, increased trading of infected animals, low level of awareness and adherence to preventive measures in some communities, and the climatic changes and other risk factors, which have possibly affected the vector and reservoir activity. Therefore, to have better control of this disease, there should be a lot of effort in close surveillance to the animals and ticks that transmit the disease and to apply stringent preventive measures. This case report reflects how the patients themselves could help save their own lives through possible self-detection or self-diagnosis. The diagnosis of the disease in the 30-year-old male patient reported here was unfortunately missed by 3 health institutions, despite the patient providing a clear history of tick bite, which was followed by typical symptoms. When the patient referred himself for the fourth time, to rule out Crimean-Congo hemorrhagic fever, the diagnosis was made. It is proposed that raising the population's knowledge and awareness about the disease would help individuals and the community at large. Self-detection or self-diagnosis of Crimean-Congo hemorrhagic fever is not impossible when patients are aware about the disease symptoms and risk factors.
Undergraduate Nursing Students' Readiness to Practice
Authors: AlMekkawi Mohamad , Khalil Rouwida El 
Published: February 2022

Background:
Nursing literature identifies difficulties facing new graduates in managing their responsibilities as registered nurses. The ability of new graduates to be practice-ready upon entry to the workplace remains a challenging concern for nurse educators.

Purpose:
This study investigated the perceptions of senior students toward their readiness to practice safely and independently and perform registered nurses' job-specific requirements upon graduation.

Methods:
A descriptive design using quantitative and qualitative methods was used to conduct the study. Data were collected from a sample of 117 senior nursing students in the United Arab Emirates using the Casey-Fink Readiness to Practice Survey.

Results:
Senior students felt confident to manage the care of 2 to 3 patients, communicate with patients and interdisciplinary teams, solve clinical problems, prioritize patients' care, and recognize significant changes in patient conditions. Areas of concern were their ability to care for more than 3 patients, among others, such as caring for dying patients and performing catheter insertion/irrigation.

Conclusion:
Students need better learning opportunities and closer guidance, support, and on-time feedback in clinical settings.
Nursing Faculty and Students' Satisfaction With Telepresence Robots During the COVID-19 Pandemic
Authors: Abuatiq Alham , Brown Robin , Plemmons Christina , Walstrom Beth , Hultman Cassy , Currier Danielle , Schmit Marie , Kvigne Valborg , Horsley Leann , Mennenga Heidi 
Published: February 2022

Background:
Telepresence robots provide real-time audio, video, and mobility features, allowing faculty and students to engage in learning experiences without being physically present.

Problem:
With multiple students and faculty members needing to quarantine due to the COVID-19 pandemic, a flexible learning environment was essential.

Approach:
The telepresence robots were used as an innovative approach for both faculty and students to engage in learning experiences offered in a variety of settings.

Outcome:
Feedback was obtained from faculty and students about the use of and satisfaction with telepresence robots. The robots were easy to use and posed only a few technological challenges, which were easily overcome.

Conclusions:
Telepresence robots were effective tools in overcoming teaching and learning barriers caused by the COVID-19 pandemic. The telepresence robots have many applications, including use in clinical and community settings.
Postoperative Urinary Incontinence in Diabetic Patients Undergoing Pelvic Reconstructive Surgery
Authors: Siddique Moiuri , Ringel Nancy E. , de Winter K. Lauren , Marczak Tara , Kisby Cassandra , Rutledge Emily , Soriano Alex , Samimi Parisa , Schroeder Michelle , Handler Stephanie , Chou Jiling , Gutman Robert E. 
Published: February 2022

Importance
Diabetes is an independent risk factor for urinary incontinence, and its impact on rates of postoperative incontinence after pelvic reconstructive surgery remains unexplored.

Objective
The aim of the study was to compare the incidence of postoperative stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence in patients with diabetes mellitus undergoing surgery for pelvic organ prolapse (POP) with or without SUI surgery.

Study Design
This is a secondary analysis of a multicenter retrospective cohort study involving 10 diverse medical centers that identified a cohort of women with diabetes who had prolapse and/or anti-incontinence surgery. We compared rates of postoperative urinary incontinence among patients who had surgery for prolapse and incontinence versus surgery for prolapse only.

Results
Three hundred five patients had surgery for prolapse and incontinence, 330 had surgery for prolapse only, and 189 had anti-incontinence surgery only. De novo UUI was higher among those who underwent surgery for POP and SUI compared with surgery for POP alone (26.4% vs 14.1%, P < 0.01). Rates of persistent SUI (21% vs 4.9%, P < 0.01) and mixed urinary incontinence (15.9% vs 2.7%, P < 0.01) were higher for those who underwent prolapse surgery alone versus prolapse and an incontinence procedure. No differences were seen in hemoglobin A1C levels between those who did and did not report postoperative UI.

Conclusions
We found that postoperative de novo UUI rates were high among patients with diabetes after pelvic reconstructive surgery, with the incidence being significantly higher for those who had surgery for prolapse and incontinence compared with surgery for prolapse only.
Frequency of FLCN Loss of Function Variants and Birt-Hogg-Dubé-Associated Phenotypes in a Healthcare System Population
Authors: Savatt Juliann M. , Shimelis Hermela , Moreno-De-Luca Andres , Strande Natasha T. , Oetjens Matthew T. , Ledbetter David H. , Martin Christa Lese , Myers Scott M. , Finucane Brenda M. 
Published: February 2022

AbstractPurposeCurrent penetrance estimates of Birt-Hogg-Dubé (BHD)-associated cutaneous, pulmonary, and renal manifestations are based on clinically ascertained families. In a healthcare system population, we used a genetics-first approach to estimate the prevalence of pathogenic/likely pathogenic (P/LP) variants in the FLCN gene, which cause BHD, and the penetrance of BHD-related phenotypes.MethodsExomes from 135,990 patient-participants in Geisinger’s MyCode® cohort were assessed for P/LP FLCN variants. BHD-related phenotypes were evaluated from electronic health records. Association between FLCN P/LP variants and BHD-related phenotypes were assessed by Firth’s logistic regression.ResultsP/LP FLCN variants were identified in 35 (1 in 3,234) individuals, 68.6% of whom had BHD-related phenotype(s) including: cystic lung disease (65.7%); pneumothoraces (17.1%); cutaneous manifestations (8.6%); and renal cancer (2.9%). Only four (11.4%) were clinically diagnosed with BHD.ConclusionIn this healthcare population, the frequency of P/LP FLCN variants is 60 times higher than the previously reported prevalence. Although most variant-positive individuals had BHD-related phenotypes in the EHR, a minority were clinically diagnosed with BHD, likely because cutaneous manifestations, pneumothoraces, and renal cancer were observed at lower frequencies than clinical cohorts. Improved clinical recognition of cystic lung disease and education concerning its association with FLCN variants could prompt evaluation for BHD.
6S RNA-dependent antibiotic susceptibility
Authors: Esberard Marick , Hallier Marc , Liu Wenfeng , Morvan Claire , Bossi Lionello , Figueroa-Bossi Nara , Felden Brice , Bouloc Philippe 
Published: February 2022

AbstractBacterial small RNAs (sRNAs) contribute to a variety of regulatory mechanisms that modulate wide ranging pathways, including metabolism, virulence, and antibiotic resistance. We investigated the involvement of sRNAs in rifampicin resistance in the opportunistic pathogenStaphylococcus aureus. Using a competition assay with an sRNA mutant library, we identified 6S RNA as being required for protection against low concentrations of rifampicin, an RNA polymerase (RNAP) inhibitor. This effect applied to rifabutin and fidaxomicin, two other RNAP-targeting antibiotics. 6S RNA is highly conserved in bacteria and its absence in two other major pathogens,Salmonella entericaandClostridioides difficile, also impaired susceptibility to RNAP inhibitors. InS. aureus, 6S RNA is produced from an autonomous gene and accumulates in stationary phase. In contrast to what was reported inEscherichia coli, S. aureus6S RNA does not appear to play a critical role in the transition from exponential to stationary phase, but affects σB-regulated expression in prolonged stationary phase. Nevertheless, its protective effect against rifampicin is independent of alternative sigma factor σBactivity. Our results suggest that 6S RNA helps maintain RNAP-σAintegrity inS. aureus, which could in turn help bacteria withstand low concentrations of RNAP inhibitors.
The impact of multigenerational high-fat diet feeding on the gut microbiome and host metabolism
Authors: Wibowo Marsha C. , Yang Zhen , Chavkin Theodore A. , Nguyen Brian , Pham Loc-Duyen , Huang Tian Lian , Lynes Matthew D. , Tseng Yu-Hua , Kostic Aleksandar D. 
Published: February 2022

AbstractAlthough human genetics partially explain the heritability of obesity and type 2 diabetes (T2D), the human gut microbiome also plays a significant role. While changes in human genetics at the population level occur only after many generations, the gut microbiome evolves over a shorter time span. The gut microbiome is also vertically transmitted across generations, therefore, changes in one generation can be passed on to subsequent generations. However, it is unknown whether the gut microbiome influences natural selection of its host under obesogenic pressure. Here, we show that C57BL/6 mice fed a high-fat diet (60% fat, HFD) over four generations develop resistance to obesity and the metabolic syndrome (MetS). Unexpectedly, the mice were increasingly leaner as well as more glucose tolerant and insulin sensitive across generations. This phenomenon was attributed to the most obese mice not yielding progenies, whereas the leanest mice successfully reproduced, and their offspring were also resistant to obesity. In other words, a population bottleneck was observed. Because all the mice were nearly genetically identical inbred C57BL/6J mice, the large variation in body weight gain in response to HFD feeding was likely independent of genetics. We explored whether microbial factors enriched in obesity-resistant mice promote healthier host metabolic phenotypes under HFD feeding, thereby contributing to the heterogeneity in body weight gain and providing an adaptive advantage to the host. Pearson correlation analysis revealed that body weight gain was positively correlated with Lactococcus lactis, as well as negatively correlated with Lactobacillus johnsonii and pathways for coenzyme A biosynthesis, amino acid biosynthesis (lysine, isoleucine, valine), and nucleotide biosynthesis (adenosine, guanosine). Overall, we observed multigenerational adaptation in the gut microbiome correlated with improved metabolism, yet further studies are needed to validate that these adaptations drive metabolic health.
Maternal transfer and long-term population effects of PCBs in Baltic grey seals using a new toxicokinetic-toxicodynamic population model
Authors: Mauritsson Karl , Desforges Jean-Pierre , Harding Karin C. 
Published: February 2022

AbstractEmpirical evidence has shown that historical exposure of polychlorinated biphenyls (PCBs) to Baltic grey seals not only severely affected individual fitness, but also population growth rates and most likely caused the retarded recovery rate of the depleted population for decades. We construct a new model which we term a toxicokinetic-toxicodynamic (TKTD) population model to quantify these effects. The toxicokinetic sub model describes in detail the bioaccumulation, elimination, and vertical transfer from mother to offspring of PCBs, and was linked to a toxicodynamic model for estimation of PCB-related damage, hazard, and stress impacts on fertility and survival rates. Both sub-models were then linked to a Leslie matrix population model to calculate changes in population growth rate and age structure given different rates of PCB exposure. Toxicodynamic model parameters related to reproductive organ lesions were calibrated using published historical data on observed pregnancy rates in Baltic grey seal females. Our model showed that increased PCB exposure caused reduced fertility, decreased vertical transfer, and increased biomagnification. Compared to empirical data, the TKTD population model described well the age-specific bioaccumulation pattern of PCBs in Baltic grey seals, and thus, the toxicokinetic parameters, deduced from literature, are believed to be reliable. The model also captured well the general effects of PCBs on historical population growth rates. The developed model can be used to perform population viability analyses of Baltic grey seals with multiple stressors, also including by-catches and different hunting regimes. The model can also be extended to other marine mammals and other contaminants than PCB by adjustments of model parameter values and thus provides a test bed in silico for new substances.
Positive and relaxed selective pressures have both strongly influenced the evolution of cryonotothenioid fishes during their radiation in the freezing Southern Ocean
Authors: Bilyk Kevin T. , Zhuang Xuan , Papetti Chiara 
Published: February 2022

AbstractEvolution in the chronic cold of the Southern Ocean has had a profound influence on the physiology of cryonotothenioid fishes. However, the suite of genetic changes underlying the physiological gains and losses in these fishes is still poorly surveyed. Using molecular evolution techniques, this study aimed to identify which functional classes of genes changed during the cryonotothenioid radiation in a polar ocean. The influences of both positive and relaxed selective pressures were isolated following two major physiological transitions: the onset of freezing temperatures, and the loss of hemoproteins. Looking at the influence of cold temperatures, positive selective pressure was most prominently found to act on biosynthetic processes (the machinery of transcription and translation) as well as on protein polymerization, cell adhesion, and cell cycle progression, suggesting these are key challenges to life in freezing waters. Relaxation of selective pressure produced a more complex pattern of change, affecting several homeostatic processes, suggesting their attenuation in cold-stable and oxygen-rich waters, but also seemingly acting as a route to key genetic change behind the morphological and ecological diversification seen in the clade. Finally, while chronic cold-water temperatures appear to have instigated clear genetic change, the loss of hemoproteins led to little observable change relative to their red-blooded relatives. Combined, the influence of positive and relaxed selection show that long-term exposure to cold has led to profound changes in cryonotothenioid genomes, which may make it challenging for them to respond to unpredictable heat waves and to adapt to a rapidly changing climate.
Dissociable Roles of FEF Neurons in Initiating Saccades
Authors: Shams-Ahmar Mohammad , Thier Peter , Merrikhi Yaser 
Published: February 2022

AbstractThe frontal eye field (FEF) plays a key role in initiating saccades. To explain how single neurons in this region may enable the initiation of saccades, Jeffery Schall proposed the “variable rate model” (Hanes and Schall, 1996) which assumes that the discharge of a neuron must reach a fixed activation threshold for a saccade to be evoked. However, the validity of this model has been questioned as results from later work testing saccades in different behavioral contexts seemed to require the assumption of variable thresholds. Moreover, even when sticking to the original behavioral context, not all types of frontal eye field neurons seemed to behave according to a variable rate model. In an attempt to reconsider the viability of the variable rate model avoiding limitations of previous research, we studied single neurons recorded from the FEF of two rhesus monkeys while they performed a memory-guided saccade task. We evaluated the degree to which each type of FEF neurons complied with the variable rate model by quantifying how precisely their discharge predicted an imminent saccade based on their immediate presaccadic activity. In addition, we asked whether there might be a hierarchical relation between visuomotor and motor neurons with only the latter responsible for the release of saccades and therefore satisfying the assumption of the variable rate model. We show that decoders trained on single motor neurons’ presaccadic activity performed better than decoders trained on visuomotor neurons in predicting an imminent saccade, in line with the assumption of a top position in a putative processing hierarchy. While this position might have suggested significant resilience to perturbation of the visual input to the FEF, we found quite the opposite that motor neurons but not visuomotor neurons were susceptible to perturbation. As a matter of fact, they lost the ability to predict the initiation of a saccade based on their immediate pressacadic discharge rate. Our results support the notion that motor neurons and visuomotor neurons have dissociable functions in information processing for saccades with motor neurons more closely related to saccade initiation, in line with the tenets of the variable rate model. Yet, they also clearly indicate that even these supposedly top layer neurons exhibit an unexpected degree of dependence on afferent input questions the viability of the assumption of a simple processing hierarchy.
CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation
Authors: Sung Pei-Shan , Yang Shao-Ping , Peng Yu-Chun , Sun Cheng-Pu , Tao Mi-Hwa , Hsieh Shie-Liang 
Published: February 2022

AbstractCoronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Autopsy demonstrates the presence of thrombosis and microangiopathy in the small vessels and capillaries. Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS. It has been shown that sera from individuals with COVID-19 triggered NET release in vitro, and spleen tyrosine kinase (Syk) inhibitor R406 inhibited NETosis caused by COVID-19 plasma. However, the serum components responsible for NET formation are still unknown. In this study, we found that virus-free extracellular vesicles (EVs) from COVID-19 patients (COVID-19 EVs) induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A). Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation and lung fibrosis were attenuated dramatically in clec5a-/-/tlr2-/- mice. These results suggest that COVID-19 EVs play critical roles in SARS-CoV-2-induced immunothrombosis, and blockade of CLEC5A and TLR2 is a promising strategy to inhibit SARS-CoV-2-induced intravascular coagulopathy and reduce the risk of ARDS in COVID-19 patients.
Expanded transcriptomic analysis of human hepatic stellate cells links novel coding and noncoding products to human liver fibrosis
Authors: Mahpour Amin , Mullen Alan 
Published: February 2022

AbstractEnd stage liver disease and liver failure occur primarily as a consequence of progressive fibrosis resulting from chronic liver injury. Hepatic stellate cells (HSCs) are the primary cell type responsible for production of the extracellular matrix (ECM) that forms the fibrotic scar. While the essential role of HSCs is understood, there remain no treatments that target HSCs to inhibit the development or progression of fibrosis. We have performed analysis of the transcriptome of human HSCs to define the long noncoding (lnc) RNAs expressed in this cell type, including many not previously annotated. Through analysis of full-length RNA transcripts, we identified additional lncRNAs that were not assembled by short reads. We also discovered new isoforms of proteincoding genes that encode amino acid sequences that are not present in annotated isoforms. Analysis of non-polyadenylated RNAs did not identify additional genes encoding long noncoding RNA transcripts, but did reveal the presence of hundreds of circular (circ) RNAs, including those with potential for translation. Incorporating these transcripts and genes into analysis of a published dataset of human liver fibrosis revealed the induction of lncRNAs, novel protein isoforms, and circRNAs associated with development of disease. These results identify RNAs and amino acid sequences expressed in HSCs and associated with human liver disease that may serve as therapeutic targets to inhibit fibrosis or biomarkers to benchmark progression of disease.