bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of culture-dependent native microbiota in Zika virus infection in Aedes aegypti
Authors: do Nascimento Rêgila Mello , Campolina Thais Bonifácio , Chaves Barbara Aparecida , Delgado Jessica Lana Fernandes , Godoy Raquel Soares Maia , Pimenta Paulo Filemon Paolucci , Secundino Nagila Francinete Costa 
Published: February 2022

AbstractBackgroundEmerging and re-emerging vector-borne diseases (VBDs) pose a recurring threat to tropical countries, mainly due to the abundance and distribution of theAedes aegyptimosquito, which is a vector of the Zika, dengue, chikungunya, and yellow fever arboviruses.MethodsFemale 3–5 day-oldAe. aegyptiwere distributed into two experimental groups: group I—survey of cultivable bacteria; sucrose group: fed only on sucrose, i.e., non-blood-fed (UF); blood-fed group: (i) fed with non-infected blood (BF); (ii) fed with blood infected with the Zika virus (BZIKV); (iii) pretreated with penicillin/streptomycin (pen/strep), and fed with non-infected blood (TBF); (iv) pretreated with pen/strep and fed blood infected with ZIKV, i.e., gravid with developed ovaries, (TGZIKV); group II—experimental co-infections: bacteria genera isolated from the group fed on sucrose, i.e., non-blood-fed (UF).ResultsUsing the cultivable method and the same mosquito colony and ZIKV strain described by in a previous work, our results reveled 11 isolates (Acinetobacter,Aeromonas,Cedecea,Cellulosimicrobium,Elizabethkingia,Enterobacter,Lysinibacillus,Pantoea,Pseudomonas,Serratia, andStaphylococcus).Enterobacterwas present in all evaluated groups (i.e., UF, BF, BZIKV, TBF, and TGZIKV), whereasElizabethkingiawas present in the UF, BZIKV, and TBF groups.Pseudomonaswas present in the BZIKV and TBF groups, whereasStaphylococcuswas present in the TBF and TGZIKV groups. The only genera of bacteria that were found to be present in only one group wereAeromonas,Lysinibacillus, andSerratia(UF);Cedacea,PantoeaandAcinetobacter(BF); andCellulosimicrobium(BZIKV). The mosquitoes co-infected with ZIKV plus the isolates group fed on sucrose (UF) showed interference in the outcome of infection.ConclusionsWe demonstrate that the distinct feeding aspects assessed herein influence the composition of bacterial diversity. In the co-infection, among ZIKV,Ae. aegyptiand the bacterial isolates, the ZIKV/Lysinibacillus–Ae. aegyptihad the lowest number of viral copies in the head-SG, which means that it negatively affects vector competence. However, when the saliva was analyzed after forced feeding, no virus was detected in the mosquito groups ZIKV/Lysinibacillus–Lu. longipalpisandAe. aegypti; the combination of ZIKV/Serratiamay interfere in salivation. This indicates that the combinations do not produce viable viruses and may have great potential as a method of biological control.Graphical Abstract
Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19
Authors: Ma Yunlong , Qiu Fei , Deng Chunyu , Li Jingjing , Huang Yukuan , Wu Zeyi , Zhou Yijun , Zhang Yaru , Xiong Yichun , Yao Yinghao , Zhong Yigang , Qu Jia , Su Jianzhong 
Published: February 2022

AbstractBackgroundUnderstanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.MethodsWe constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N= 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N= 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells.ResultsWe found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes ofCCR1,CXCR6, andABOwere highly expressed in these three cell types, respectively.CCR1+CD16+monocytes andABO+megakaryocytes with significantly up-regulated genes, includingS100A12,S100A8,S100A9, andIFITM1, confer higher risk to the dysregulated immune response among severe patients.CXCR6+memory CD8+ T cells exhibit a notable polyfunctionality including elevation of proliferation, migration, and chemotaxis. Moreover, we observed an increase in cell-cell interactions of bothCCR1+CD16+monocytes andCXCR6+memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues. The enhanced interactions ofCXCR6+memory CD8+T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+T cell-mediated immunity against COVID-19 infection.ConclusionsWe uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
A multi-step approach to managing missing data in time and patient variant electronic health records
Authors: Cesare Nina , Were Lawrence P. O. 
Published: February 2022

Abstract
Objective
Electronic health records (EHR) hold promise for conducting large-scale analyses linking individual characteristics to health outcomes. However, these data often contain a large number of missing values at both the patient and visit level due to variation in data collection across facilities, providers, and clinical need. This study proposes a stepwise framework for imputing missing values within a visit-level EHR dataset that combines informative missingness and conditional imputation in a scalable manner that may be parallelized for efficiency.

Results
For this study we use a subset of data from AMPATH representing information from 530,812 clinic visits from 16,316 Human Immunodeficiency Virus (HIV) positive women across Western Kenya who have given birth. We apply this process to a set of 84 clinical, social and economic variables and are able to impute values for 84.6% of variables with missing data with an average reduction in missing data of approximately 35.6%. We validate the use of this imputed dataset by predicting National Hospital Insurance Fund (NHIF) enrollment with 94.8% accuracy.
Correction of carotid artery stenosis by stent placement ameliorated paroxysmal hypertension after radiation treatment of hypopharyngeal carcinoma: a case report
Authors: Brook Itzhak , Cohen Ezra , Stemer Andrew 
Published: February 2022

AbstractBackgroundParoxysmal hypertension can be associated with failure of the carotid artery baroreceptors due to past exposure to radiation treatment. This report describes a patient whose repeated paroxysmal hypertensive episodes were ameliorated following placement of a carotid artery stent for the treatment of carotid artery stenosis.Case reportA 79-year-old caucasian male was diagnosed with hypopharyngeal squamous cell carcinoma (T1, L0, M0) in 2006, and received 70 Gy intensity-modulated radiotherapy in 2006 and underwent a total laryngectomy in 2008. He experienced paroxysmal hypertensive episodes since 2010 that exacerbated in frequency in 2019. Eighty percent left internal carotid artery stenosis was demonstrated by ultrasound and arteriography. Angioplasty and stenting of the left carotid artery was performed. A Doppler ultrasound study performed 5 months after the stent placement did not reveal any hemodynamic stenosis in the left carotid artery. The patient experienced postprandial hypotension and had experienced only three episodes of paroxysmal hypertension in the following 24 months. He was able to abort paroxysmal hypertensive episodes by eating warm food.DiscussionThis is the first report of a patient whose paroxysmal hypertensive episodes that occurred following radiation of the neck subsided after placement of a stent in a stenotic carotid artery. The exact mechanism leading to this phenomena is unknown but may be due to several factors. The reversal of the carotid artery stent and improvement in blood flow to the carotid artery baroceptors may play a role in this phenomenon.ConclusionThe ability to ameliorate paroxysmal hypertensive episodes in a patient with carotid artery stenosis by stent placement may be a promising therapeutic intervention for paroxysmal hypertension.
Is it time to reconsider the administration of thiamine alone or in combination with vitamin C in critically ill patients? A meta-analysis of clinical trial studies
Authors: Shokri-mashhadi Nafiseh , Aliyari Ali , Hajhashemy Zahra , Saadat Saeed , Rouhani Mohammad Hossein 
Published: February 2022

AbstractBackgroundAlthough the effect of thiamine alone or in combination with vitamin C has been studied in multiple trials (RCT and interventional studies), their results are inconsistent. This meta-analysis aimed to assess impact of thiamine administration alone, thiamine in combination with vitamin C, and co-administration of low-dose hydrocortisone, vitamin C and thiamine (HVT) on clinical outcomes in critically ill patients.Methods and materialsAfter electronic searches on PubMed, Scopus, Cochrane Library, and Web of Science databases, initially 3367 papers were found, and 20 interventional studies were included in our analysis. We assessed the risk-difference between treatment and control (standard treatment) groups by pooling available data on ICU length of stay, number of ventilator free days, mortality, and changes in Sequential Organ Failure Assessment (SOFA) scores.ResultsThe results of present studies revealed no significant effect of thiamine in combination with vitamin C, and HVT on number of free days of ventilation. Thiamine alone supplementation was associated with high mortality percentage (WMD: 5.17%; 95% CI: 2.67, 7.67). Thiamine in combination with vitamin C had no significant impact on mortality rate. In contrast, HVT could decrease mortality rate (WMD: − 7.23%; 95% CI: − 10.31, − 4.16; I-square: 0.0%). There was no significant effect of thiamine alone, co-administration of thiamine and vitamin C, and HVT on ICU length of stay. The results of the meta-analysis showed that thiamine alone and HVT supplementation had no significant effect on SOFA score. Interestingly, co-supplementation of thiamine and vitamin C had a significant decreasing effect on SOFA score (WMD: − 0.73; 95% CI: − 1.29, − 0.17; I-square: 0.0%).ConclusionIn contrast to HVT, thiamine supplementation alone was associated with increased mortality rate in ICU. However, co-supplementation of thiamine and vitamin C had a significant decreasing effect on SOFA score.
In silico analyses of maleidride biosynthetic gene clusters
Authors: Williams Katherine , de Mattos-Shipley Kate M. J. , Willis Christine L. , Bailey Andrew M. 
Published: February 2022

AbstractMaleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the ‘core’ set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways.
Concurrent wasting and stunting among children 6–59 months: an analysis using district-level survey data in Mozambique
Authors: Zaba Tomás , Conkle Joel , Nyawo Mara , Foote Dorothy , Myatt Mark 
Published: February 2022

Abstract
Background
In the past it was believed that wasting and stunting were independent of each other. Recent work has shown that they can occur concurrently in a child and that increases considerably the risk of mortality. Concurrent wasting and stunting (WaSt) is currently defined as WHZ < -2 AND HAZ < -2. Wasting is measured by WHZ and MUAC and evidence shows that they tend to identify different sets of children. Our study aimed to look at the effect of adding MUAC on the prevalence and burden of WaSt, and to assess diagnosis of WaSt with a single measurement.

Methods
We analyzed population-based anthropometric surveys from 37 districts in Mozambique conducted by the Government of Mozambique between 2017 and 2019. We proposed a new case-definition for WaSt that includes MUAC in acknowledgement of the different children with wasting diagnosed by WHZ and MUAC. We estimated how many WaSt cases are eligible to be included in the existing treatment program in Mozambique by calculating the True Positive and False Positive Values of WaSt using our proposed case-definition against the wasting admission criteria. AUC of ROC curves used for MUAC and WAZ and optimal cut-offs were determined using Youden’s Index.

Results
Including MUAC in the concurrent WaSt case-definition identified more children with WaSt compared to the original case-definition and more younger children and girls were identified. Using both MUAC and WHZ and enrolling severe and moderate wasting is already picking up most of the WaSt cases: 100% in health facilities and 79.40% with MUAC mass screenings at community level. Cut-off values from the ROC curve for the proposed case-definition were MUAC ≤133 mm and WAZ ≤ 2.145 Z-scores, however, they yielded many false positive values.

Conclusion
WaSt case-definition should include MUAC. WaSt should commence to be reported in surveys and Mozambique should also start monitoring and treating children with WaSt. A cost-effective approach to identify all children with WaSt without adding too many false positive is needed, as well as understanding how to achieve optimal treatment outcomes within existing programs.
The effect of low-frequency repetitive transcranial magnetic stimulation on left dorsolateral prefrontal cortex in patients with the obsessive-compulsive disorder: a double-blinded, sham-controlled clinical trial
Authors: Diarjani Adeleh Askari , Javadi Seyed Alireza Haji Seyed 
Published: February 2022

Abstract
Background
Obsessive-compulsive disorder (OCD) is a complicated neuropsychiatric disorder, which its prevalence ranges from 2 to 4%. In 30–60% of patients due to intolerance of side effects or partial response to treat symptoms of the disease remain or relapse. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapeutic option to treat this condition. Transcranial magnetic stimulation can be applied for treating with no anesthesia. The current study intended to evaluate the effectiveness of low-frequency rTMS on the left dorsolateral prefrontal cortex as an adjunct treatment in combination with standard medication in patients with OCD.

Results
In both groups of intervention and sham, the Y-BOCS scale was decreased. There was no significant difference between the two groups (P=0.82). Also after 15 sessions, the symptoms of OCD patients were improved. Although the treatment process was the same in the control group, none of the patients showed any serious complications, such as seizures, severe headache, neurological complication, or cognitive impairment during treatment.

Conclusions
It seems that treatment with 1 Hz rTMS on the left dorsolateral prefrontal cortex does not play an effective role in the recovery of OCD patients.

Trial registration
Name of the registry: Therapeutic effect comparison of the Repetitive Transcranial MagneticMagnetic Stimulation (RTMS) combination therapy with drug versus medication monotherapy in obsessive-compulsive disorder (OCD). Trial registration number: IRCT ID: IRCT20200728048240N1. Date of registration: 2020/8/8.
Predicting patients who will drop out of out-patient psychotherapy using machine learning algorithms
Authors: Bennemann Björn , Schwartz Brian , Giesemann Julia , Lutz Wolfgang 
Published: February 2022

BackgroundAbout 30% of patients drop out of cognitive–behavioural therapy (CBT), which has implications for psychiatric and psychological treatment. Findings concerning drop out remain heterogeneous.AimsThis paper aims to compare different machine-learning algorithms using nested cross-validation, evaluate their benefit in naturalistic settings, and identify the best model as well as the most important variables.MethodThe data-set consisted of 2543 out-patients treated with CBT. Assessment took place before session one. Twenty-one algorithms and ensembles were compared. Two parameters (Brier score, area under the curve (AUC)) were used for evaluation.ResultsThe best model was an ensemble that used Random Forest and nearest-neighbour modelling. During the training process, it was significantly better than generalised linear modelling (GLM) (Brier score: d = –2.93, 95% CI (−3.95, −1.90)); AUC: d = 0.59, 95% CI (0.11 to 1.06)). In the holdout sample, the ensemble was able to correctly identify 63.4% of cases of patients, whereas the GLM only identified 46.2% correctly. The most important predictors were lower education, lower scores on the Personality Style and Disorder Inventory (PSSI) compulsive scale, younger age, higher scores on the PSSI negativistic and PSSI antisocial scale as well as on the Brief Symptom Inventory (BSI) additional scale (mean of the four additional items) and BSI overall scale.ConclusionsMachine learning improves drop-out predictions. However, not all algorithms are suited to naturalistic data-sets and binary events. Tree-based and boosted algorithms including a variable selection process seem well-suited, whereas more advanced algorithms such as neural networks do not.
Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
Authors: Raina Dhruv , Fabris Fiorella , Morelli Luis G. , Schröter Christian 
Published: February 2022

ABSTRACT
Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.
The RASopathies: from pathogenetics to therapeutics
Authors: Hebron Katie E. , Hernandez Edjay Ralph , Yohe Marielle E. 
Published: February 2022

ABSTRACT
The RASopathies are a group of disorders caused by a germline mutation in one of the genes encoding a component of the RAS/MAPK pathway. These disorders, including neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome and Legius syndrome, among others, have overlapping clinical features due to RAS/MAPK dysfunction. Although several of the RASopathies are very rare, collectively, these disorders are relatively common. In this Review, we discuss the pathogenesis of the RASopathy-associated genetic variants and the knowledge gained about RAS/MAPK signaling that resulted from studying RASopathies. We also describe the cell and animal models of the RASopathies and explore emerging RASopathy genes. Preclinical and clinical experiences with targeted agents as therapeutics for RASopathies are also discussed. Finally, we review how the recently developed drugs targeting RAS/MAPK-driven malignancies, such as inhibitors of RAS activation, direct RAS inhibitors and RAS/MAPK pathway inhibitors, might be leveraged for patients with RASopathies.
Cardiorespiratory Fitness, BMI, Mortality, and Cardiovascular Disease in Adults with Overweight/Obesity and Type 2 Diabetes
Authors: WILLS ANDREW C. , VAZQUEZ ARREOLA ELSA , OLAIYA MUIDEEN T. , CURTIS JEFFREY M. , HELLGREN MARGARETA I. , HANSON ROBERT L. , KNOWLER WILLIAM C. 
Published: February 2022

ABSTRACT

Introduction
We estimated the effects of cardiorespiratory fitness (CRF) and body mass index (BMI) at baseline on mortality and cardiovascular disease events in people with type 2 diabetes who participated in the Look AHEAD randomized clinical trial.

Methods
Look AHEAD compared effects of an intensive lifestyle intervention with diabetes support and education on cardiovascular disease events in 5145 adults age 45–76 yr with overweight/obesity and type 2 diabetes. In 4773 participants, we performed a secondary analysis of the association of baseline CRF during maximal treadmill test (expressed as metabolic equivalents (METs)) on mortality and cardiovascular disease events during a mean follow-up of 9.2 yr.

Results
The mean (SD) CRF was 7.2 (2.0) METs. Adjusted for age, sex, race/ethnicity, BMI, intervention group, and β-blocker use, all-cause mortality rate was 30% lower per SD greater METs (hazard ratio (HR) = 0.70 (95% confidence interval, 0.60 to 0.81); rate difference (RD), −2.71 deaths/1000 person-years (95% confidence interval, −3.79 to −1.63)). Similarly, an SD greater METs predicted lower cardiovascular disease mortality (HR, 0.45; RD, −1.65 cases/1000 person-years) and a composite cardiovascular outcome (HR, 0.72; RD, −6.38). Effects of METs were homogeneous on the HR scale for most baseline variables and outcomes but heterogeneous for many on the RD scale, with greater RD in subgroups at greater risk of the outcomes. For example, all-cause mortality was lower by 7.6 deaths/1000 person-years per SD greater METs in those with a history of cardiovascular disease at baseline but lower by only 1.6 in those without such history. BMI adjusted for CRF had little or no effect on these outcomes.

Conclusions
Greater CRF is associated with reduced risks of mortality and cardiovascular disease events.