bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning–Based Mortality Prediction of Patients at Risk During Hospital Admission
Authors: Trentino Kevin M. , Schwarzbauer Karin , Mitterecker Andreas , Hofmann Axel , Lloyd Adam , Leahy Michael F. , Tschoellitsch Thomas , Böck Carl , Hochreiter Sepp , Meier Jens 
Published: January 2022

Objectives
The ability to predict in-hospital mortality from data available at hospital admission would identify patients at risk and thereby assist hospital-wide patient safety initiatives. Our aim was to use modern machine learning tools to predict in-hospital mortality from standardized data sets available at hospital admission.

Methods
This was a retrospective, observational study in 3 adult tertiary care hospitals in Western Australia between January 2008 and June 2017. Primary outcome measures were the area under the curve for the receiver operating characteristics curve, the F
1 score, and the average precision of the 4 machine learning algorithms used: logistic regression, neural networks, random forests, and gradient boosting trees.

Results
Using our 4 predictive models, in-hospital mortality could be predicted satisfactorily (areas under the curve for neural networks, logistic regression, random forests, and gradient boosting trees: 0.932, 0.936, 0.935, and 0.935, respectively), with moderate F
1 scores: 0.378, 0.367, 0.380, and 0.380, respectively. Average precision values were 0.312, 0.321, 0.334, and 0.323, respectively. It remains unknown whether additional features might improve our models; however, this would result in additional efforts for data acquisition in daily clinical practice.

Conclusions
This study demonstrates that using only a limited, standardized data set in-hospital mortality can be predicted satisfactorily at the time point of hospital admission. More parameters describing patient’s health are likely needed to improve our model.
Increased 68Ga-FAPI Uptake in Facet Joint Osteoarthritis in a Patient With Esophageal Cancer
Authors: Yang Xiao , You Zhouxiang , Gong Weidong , Chen Yue , Liu Huipan 
Published: January 2022

Abstract
A 69-year-old man presented with newly diagnosed esophageal cancer was enrolled in our clinical trial of 68Ga-FAPI PET/CT study in tumors. Increased tracer uptake was noted in esophageal cancer. In addition, the facet joint osteoarthritis of T7/8 vertebrae also revealed elevated 68Ga-FAPI uptake.
Progressive Multifocal Leukoencephalopathy Mimicking Malignancy on 68Ga-FAPI PET/CT
Authors: Gong Weidong , Fu Meng , Zhang Yaling , Yang Xiao , Zhang Chunyin 
Published: January 2022

Abstract
A 43-year-old man presented with weakness in his right upper limb for 2 months. Head MRI showed intracranial multiple abnormal signal foci. Malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68Ga-FAPI PET/CT. 68Ga-FAPI PET/CT showed intracranial multiple FAPI-avid foci. It was also highly suggestive of malignancy. However, the combination of clinical manifestations, imaging findings, cerebral spinal fluid examinations, and effective immunotherapy confirmed the diagnosis of progressive multifocal leukoencephalopathy. 68Ga-FAPI may have potential advantages in the diagnosis of progressive multifocal leukoencephalopathy.
Quality and Safety in Healthcare, Part XCIII
Authors: Harolds Jay A. 
Published: January 2022

Abstract
Design for Six Sigma (DFSS) is used to design new outputs such as manufactured products or to design new processes. The steps in DFSS are define, measure, analyze, design, and verify. Many sophisticated statistical tools are often used. There are advantages and disadvantages of both Lean and Six Sigma, and often a blending of the 2 methodologies are used in the Lean Six Sigma methodology.
Lymphogranuloma Venereum Mimicking Lymphoma on FDG PET/CT
Authors: Georgopoulou Angeliki N. , Skoura Evangelia , Lakiotaki Eleftheria , Sipsas Nikolaos V. , Vassilakopoulos Theodoros P. 
Published: January 2022

Abstract
A 42-year-old man presented with painless, left inguinal lymphadenopathy, which was suspicious of malignant lymphoma. Multiple left-sided foci of markedly increased metabolic activity were observed on PET/CT (SUVmax up to 22.3), located at the inguinal, iliac, and para-aortic lymph nodes along with small-sized right inguinal lymphadenopathy. Laboratory tests revealed increased inflammation markers and neutrophilic leukocytosis. Pathological examination from dissected inguinal lymph node was consistent with granulomatous disease. Infection by chlamydia trachomatis was made serologically establishing the diagnosis of lymphogranuloma venereum.
Increased 68Ga-FAPI Uptake in Avascular Necrosis of Femoral Head in a Patient With Nasopharyngeal Carcinoma
Authors: Liu Huipan , Fu Wenhui , Yang Xiao , Chen Yue 
Published: January 2022

Abstract
A 73-year-old man with newly diagnosed nasopharyngeal carcinoma included in a clinical trial of 68Ga-FAPI PET/CT study in tumors (ChiCTR2100044131). Increased tracer uptake was noted in nasopharyngeal carcinoma and cervical lymph nodes metastases. In addition, avascular necrosis of right femoral head also revealed increased FAPI activity.
Similar Findings on 18F-MFBG PET/CT and 68Ga-DOTATATE PET/CT in a Patient With Widespread Metastatic Pheochromocytoma
Authors: Wang Peipei , Hou Guozhu , Jing Hongli , Zhuang Hongming , Li Fang 
Published: January 2022

Abstract
A 27-year-old woman with known malignant pheochromocytoma was enrolled in a clinical trial to compare efficacy of 68Ga-DOTATATE PET/CT and 18F-MFBG PET/CT. Images from both studies detected similar number of the metastatic lesions. In addition, both studies detected more lesions than 131I-MIBG imaging.
Deep Proteome Profiling Enabled Functional Annotation and Data-Independent Quantification of Proline Hydroxylation Targets
Authors: Gong Yao , Behera Gaurav , Erber Luke , Luo Ang , Chen Yue 
Published: January 2022

AbstractProline hydroxylation (Hyp) regulates protein structure, stability and protein-protein interaction and is widely involved in diverse metabolic and physiological pathways in cells and diseases. To reveal functional features of the proline hydroxylation proteome, we integrated various data sources for deep proteome profiling of proline hydroxylation proteome in human and developed HypDB (https://www.HypDB.site), an annotated database and web server for proline hydroxylation proteome. HypDB provides site-specific evidence of modification based on extensive LC-MS analysis and literature mining with 15319 non-redundant Hyp sites and 8226 sites with high confidence on human proteins. Annotation analysis revealed significant enrichment of proline hydroxylation on key functional domains and tissue-specific distribution of Hyp abundance across 26 types of human organs and fluids and 6 cell lines. The network connectivity analysis further revealed a critical role of proline hydroxylation in mediating protein-protein interactions. Moreover, the spectral library generated by HypDB enabled data-independent analysis (DIA) of clinical tissues and the identification of novel Hyp biomarkers in lung cancer and kidney cancer. Taken together, our integrated analysis of human proteome with publicly accessible HypDB revealed functional diversity of Hyp substrates and provides a quantitative data source to characterize proline hydroxylation in pathways and diseases.
Hypercapnia limits β-catenin-mediated alveolar type 2 cell progenitor function by altering Wnt production from adjacent fibroblasts
Authors: Dada Laura A. , Welch Lynn C. , Magnani Natalia D. , Ren Ziyou , Brazee Patricia L. , Celli Diego , Flozak Annette S. , Weng Anthea , Maciel-Herrerias Mariana , Kryvenko Vitalii , Vadász István , Runyan Constance E , Abdala-Valencia Hiam , Shigemura Masahiko , Casalino-Matsuda S. Marina , Misharin Alexander V. , Budinger G.R. Scott , Gottardi Cara J. , Sznajder Jacob I. 
Published: January 2022

ABSTRACTPersistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with ARDS secondary to SARS-CoV-2 pneumonia, low tidal volumes to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here, we show that hypercapnia limits β-catenin signaling in alveolar type 2 (AT2) cells, leading to reduced proliferative capacity. Hypercapnia alters expression of major Wnts in PDGFRa+-fibroblasts from those maintaining AT2 progenitor activity and towards those that antagonize β-catenin signaling and limit progenitor function. Activation of β-catenin signaling in AT2 cells, rescues the inhibition AT2 proliferation induced by hypercapnia. Inhibition of AT2 proliferation in hypercapnic patients may contribute to impaired lung repair after injury, preventing sealing of the epithelial barrier, increasing lung flooding, ventilator dependency and mortality.
Persistence of parental age effect on somatic mutation rates across generations in Arabidopsis
Authors: Bhushan Shashi , Singh Amit Kumar , Thakur Yogendra , Baskar Ramamurthy 
Published: January 2022

AbstractIn the model plant Arabidopsis thaliana, parental age is known to affect somatic mutation rates in their immediate progeny and here we show that this age dependent effect persists across successive generations. Using a set of detector lines carrying the mutated uidA gene, we examined if a particular parental age maintained across five consecutive generations affected the rates of base substitution (BSR), intrachromosomal recombination (ICR), frameshift mutation (FS), and transposition. The frequency of functional GUS reversions were assessed in seedlings as a function of identical/different parental ages across generations. In the context of a fixed parental age, BCR/ICR rates were unaffected in the first three generations, then dropped significantly in the 4th and increased in most instances in the 5th generation. On the other hand, with advancing parental ages, BSR/ICR rates remained high in the first two/three generations, with a striking resemblance in the pattern of mutation rates. We adopted a novel approach of identifying and tagging flowers pollinated on a particular day, thereby avoiding biases due to potential emasculation induced stress responses. Our results suggest a time component in counting the number of generations a plant has passed through self-fertilization at a particular age in determining the somatic mutation rates.
Impaired spatial memory in adult vitamin D deficient BALB/c mice is associated with reductions in spine density, nitric oxide, and neural nitric oxide synthase in the hippocampus
Authors: Al-Amin Md. Mamun , Sullivan Robert K. P. , Alexander Suzy. , Carter David A. , Bradford DanaKai. , Burne Thomas H. J. 
Published: January 2022

AbstractVitamin D deficiency is prevalent in adults and is associated with cognitive impairment. However, the mechanism by which adult vitamin D (AVD) deficiency affects cognitive function remains unclear. We examined spatial memory impairment in AVD-deficient BALB/c mice and its underlying mechanism by measuring spine density, long term potentiation (LTP), nitric oxide (NO), neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the hippocampus. Adult male BALB/c mice were fed a control or vitamin D deficient diet for 20 weeks. Spatial memory performance was measured using an active place avoidance (APA) task, where AVD-deficient mice had reduced latency entering the shock zone compared to controls. We characterised hippocampal spine morphology in the CA1 and dentate gyrus (DG) and made electrophysiological recordings in the hippocampus of behaviourally naïve mice to measure LTP. We next measured NO, as well as glutathione, lipid peroxidation and oxidation of protein products and quantified hippocampal immunoreactivity for nNOS and eNOS. Spine morphology analysis revealed a significant reduction in the number of mushroom spines in the CA1 dendrites but not in the DG. There was no effect of diet on LTP. However, hippocampal NO levels were depleted whereas other oxidation markers were unaltered by AVD deficiency. We also showed a reduced nNOS, but not eNOS, immunoreactivity. Finally, vitamin D supplementation for 10 weeks to AVD-deficient mice restored nNOS immunoreactivity to that seen in in control mice. Our results suggest that lower levels of NO, reduced nNOS immunostaining contribute to hippocampal-dependent spatial learning deficits in AVD-deficient mice.
m6A-TSHub: unveiling the context-specific m6A methylation and m6A-affecting mutations in 23 human tissues
Authors: Song Bowen , Huang Daiyun , Zhang Yuxin , Wei Zhen , Su Jionglong , de Magalhães João Pedro , Rigden Daniel J. , Meng Jia , Chen Kunqi 
Published: January 2022

AbstractAs the most pervasive epigenetic marker present on mRNA and lncRNA, N6-methyladenosine (m6A) RNA methylation has been shown to participate in essential biological processes. Recent studies revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform m6A-TSHub for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB: a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tissues and 499,369 m6A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder: a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar: a web server for assessing the impact of genetic variants on tissue-specific m6A RNA modification; and (4) m6A-CAVar: a database of 587,983 TCGA cancer mutations (derived from 27 cancer types) that were predicted to affect m6A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m6A methylome and genetic factor of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at: www.xjtlu.edu.cn/biologicalsciences/m6ats.
An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer
Authors: Suryadevara Naveenchandra , Shiakolas Andrea R. , VanBlargan Laura A. , Binshtein Elad , Chen Rita E. , Case James Brett , Kramer Kevin J. , Armstrong Erica , Myers Luke , Trivette Andrew , Gainza Christopher , Nargi Rachel S. , Selverian Christopher N. , Davidson Edgar , Doranz Benjamin J. , Diaz Summer M. , Handal Laura S. , Carnahan Robert H. , Diamond Michael S. , Georgiev Ivelin S. , Crowe James E. 
Published: January 2022

SUMMARYThe protective human antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus focuses on the spike (S) protein which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor- binding domain or a single dominant epitope (‘supersite’) on the N terminal domain (NTD). Here, using the single B cell technology LIBRA-seq, we isolated a large panel of NTD-reactive and SARS-CoV-2 neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies to the NTD supersite commonly are encoded by the IGHV1-24 gene, forming a genetic cluster that represents a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited cell-to-cell spread of virus in culture, and conferred protection in human ACE2 transgenic mice against SARS-CoV-2 challenge. This study provides insight about antibody targeting of the S protein trimer interface region, suggesting this region may be a site of virus vulnerability.
COVID-19 infection and vaccination rates in healthcare workers in British Columbia, Canada: A Longitudinal Urban versus Rural Analysis of the Impact of the Vaccine Mandate
Authors: Yassi Annalee , Barker Stephen , Lockhart Karen , Taylor Deanne , Harris Devin , Hundal Harsh , Grant Jennifer M. , Okpani Arnold Ikedichi , Pollock Sue , Sprague Stacy , Sing Chad Kim 
Published: January 2022

AbstractPurposeHealthcare workers (HCWs) play a critical role in responding to the COVID-19 pandemic. Early in the pandemic, urban centres were hit hardest globally; rural areas gradually became more impacted. We compared COVID-19 infection and vaccine uptake in HCWs living in urban versus rural locations within, and between, two health authorities in British Columbia (BC), Canada. We also analyzed the impact of a vaccine mandate for HCWs.MethodsWe tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in 29,021 HCWs in Interior Health (IH) and 24,634 HCWs in Vancouver Coastal Health (VCH), by occupation, age, and home location, comparing to the general population in that region. We then evaluated the impact of infection rates as well as the mandate on vaccination uptake.ResultsBy October 27, 2021, the date that unvaccinated HCWs were prohibited from providing healthcare, only 1.6% in VCH yet 6.5% in IH remained unvaccinated. Rural workers in both areas had significantly higher unvaccinated rates compared with urban dwellers. Over 1,800 workers, comprising 6.4% of rural HCWs and 3.3% of urban HCWs, remained unvaccinated and set to be terminated from their employment. While the mandate prompted a significant increase in second doses, the impact on the unvaccinated was less clear.ConclusionsAs rural areas often suffer from under-staffing, loss of HCWs could have serious impacts on healthcare provision as well as on the livelihoods of unvaccinated HCWs. Greater efforts are needed to understand how to better address the drivers of rural-related vaccine hesitancy as the pandemic continues.
Bifidobacterium longum attenuates ovariectomy-induced bone loss via modulating the Immunoporotic “Breg-Treg-Th17” cell axis
Authors: Sapra Leena , Shokeen Niti , Gupta Konica , Saini Chaman , Bhardwaj Asha , Mathew Mary , Mishra Pradyumna K. , Chattopadhyay Naibedya , Verma Bhupendra , Srivastava Rupesh K. 
Published: January 2022

AbstractDiscoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune system. These discoveries fuel novel approaches for the treatment of several bone-pathologies including osteoporosis, an inflammatory bone anomaly affecting more than 500 million people globally. Bifidobacterium longum (BL) is preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in ovariectomy (ovx)-induced post-menopausal osteoporotic mice model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Our in vivo data clearly establish that BL exhibits osteoprotective potential via modulating the “immunoporotic” Breg-Treg-Th17 cell-axis. Furthermore, µCT and bone mechanical strength data support that BL supplementation significantly enhanced bone mass and strength, and improved microarchitecture in ovx mice. Remarkably, alteration in frequencies of CD19+CD1dhiCD5+ Bregs, CD4+Foxp3+IL-10+ Tregs, and CD4+Rorγt+IL-17+ Th17 immune cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-γ and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-α) strongly support the immunomodulatory potential of BL. Altogether our findings establish a novel osteo-protective and immunoporotic potential of BL in augmenting bone health under osteoporotic conditions.
Identification of candidate virulence loci in Striga hermonthica, a devastating parasite of African cereal crops
Authors: Qiu Suo , Bradley James M. , Zhang Peijun , Chaudhuri Roy , Blaxter Mark , Butlin Roger K. , Scholes Julie D. 
Published: January 2022

SummaryParasites have evolved proteins, Virulence Factors (VFs), that facilitate plant colonization, yet VFs mediating parasitic plant-host interactions are poorly understood. Striga hermonthica is an obligate, root-parasitic plant of cereal hosts in sub-Saharan Africa, causing devastating yield losses. Understanding the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding resistance and delaying the evolution of parasite virulence.We assembled the S. hermonthica genome and identified secreted proteins by in silico prediction. Pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host allowed us to scan for loci where selection imposed by the resistant host had elevated the frequency of alleles contributing to successful colonisation.Thirty-eight putatively secreted VFs had extremely different allele frequencies with functions including host cell wall modification, protease inhibitors, oxidoreductase and kinase activities. These candidate loci had significantly higher Tajima’s D than the genomic background, consistent with balancing selection.Our results reveal diverse strategies used by S. hermonthica to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as a part of a sustainable control strategy.