bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal annotation of the human genome through integration of over a thousand epigenomic datasets
Authors: Vu Ha , Ernst Jason 
Published: January 2022

AbstractBackgroundGenome-wide maps of chromatin marks such as histone modifications and open chromatin sites provide valuable information for annotating the non-coding genome, including identifying regulatory elements. Computational approaches such as ChromHMM have been applied to discover and annotate chromatin states defined by combinatorial and spatial patterns of chromatin marks within the same cell type. An alternative “stacked modeling” approach was previously suggested, where chromatin states are defined jointly from datasets of multiple cell types to produce a single universal genome annotation based on all datasets. Despite its potential benefits for applications that are not specific to one cell type, such an approach was previously applied only for small-scale specialized purposes. Large-scale applications of stacked modeling have previously posed scalability challenges.ResultsUsing a version of ChromHMM enhanced for large-scale applications, we apply the stacked modeling approach to produce a universal chromatin state annotation of the human genome using over 1000 datasets from more than 100 cell types, with the learned model denoted as the full-stack model. The full-stack model states show distinct enrichments for external genomic annotations, which we use in characterizing each state. Compared to per-cell-type annotations, the full-stack annotations directly differentiate constitutive from cell type-specific activity and is more predictive of locations of external genomic annotations.ConclusionsThe full-stack ChromHMM model provides a universal chromatin state annotation of the genome and a unified global view of over 1000 datasets. We expect this to be a useful resource that complements existing per-cell-type annotations for studying the non-coding human genome.
scDALI: modeling allelic heterogeneity in single cells reveals context-specific genetic regulation
Authors: Heinen Tobias , Secchia Stefano , Reddington James P. , Zhao Bingqing , Furlong Eileen E. M. , Stegle Oliver 
Published: January 2022

AbstractWhile it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore this heterogeneity or use sorted cell populations, reducing discovery and explanatory power. Here, we develop scDALI, a versatile computational framework that integrates information on cellular states with allelic quantifications of single-cell sequencing data to characterize cell-state-specific genetic effects. We apply scDALI to scATAC-seq profiles from developing F1Drosophilaembryos and scRNA-seq from differentiating human iPSCs, uncovering heterogeneous genetic effects in specific lineages, developmental stages, or cell types.
Atypical skin manifestation in severe acute chikungunya infection in a pregnant woman: a case report
Authors: Benjamanukul Saovanee , Chansaenroj Jira , Chirathaworn Chintana , Poovorawan Yong 
Published: January 2022

Abstract
Introduction
Patients with chikungunya virus infection commonly present with fever, skin rash, and severe joint pain. The vesiculobullous rash is rare in adults but common in infants. In addition, septic shock and acute respiratory distress syndrome are rare complications of atypical and severe acute chikungunya infection.

Case presentation
We report the presence of an 18-year-old Thai female, at 31 weeks gestation, with fever, maculopapular rash, and polyarthritis. The rash later progressed to a vesiculobullous pattern, and she developed septic shock and acute respiratory distress syndrome. Skin biopsy and blood were positive for chikungunya virus RNA. The patient was intubated with a mechanical ventilator and subsequently fully recovered.

Conclusion
Atypical skin manifestation and severe acute disease is likely due to immune response attenuation in pregnancy. The possibility of progression to severe or atypical disease in pregnant women suffering chikungunya should always be considered.
End-to-End provenance representation for the understandability and reproducibility of scientific experiments using a semantic approach
Authors: Samuel Sheeba , König-Ries Birgitta 
Published: January 2022

Abstract
Background
The advancement of science and technologies play an immense role in the way scientific experiments are being conducted. Understanding how experiments are performed and how results are derived has become significantly more complex with the recent explosive growth of heterogeneous research data and methods. Therefore, it is important that the provenance of results is tracked, described, and managed throughout the research lifecycle starting from the beginning of an experiment to its end to ensure reproducibility of results described in publications. However, there is a lack of interoperable representation of end-to-end provenance of scientific experiments that interlinks data, processing steps, and results from an experiment’s computational and non-computational processes.

Results
We present the “REPRODUCE-ME” data model and ontology to describe the end-to-end provenance of scientific experiments by extending existing standards in the semantic web. The ontology brings together different aspects of the provenance of scientific studies by interlinking non-computational data and steps with computational data and steps to achieve understandability and reproducibility. We explain the important classes and properties of the ontology and how they are mapped to existing ontologies like PROV-O and P-Plan. The ontology is evaluated by answering competency questions over the knowledge base of scientific experiments consisting of computational and non-computational data and steps.

Conclusion
We have designed and developed an interoperable way to represent the complete path of a scientific experiment consisting of computational and non-computational steps. We have applied and evaluated our approach to a set of scientific experiments in different subject domains like computational science, biological imaging, and microscopy.
Electronic cigarettes as a harm reduction strategy among patients with COPD: protocol for an open-label two arm randomized controlled pilot trial
Authors: Stevens Elizabeth R. , Lei Lei , Cleland Charles M. , Vojjala Mahathi , El-Shahawy Omar , Berger Kenneth I. , Kirchner Thomas R. , Sherman Scott E. 
Published: January 2022

AbstractBackgroundSmoking cessation is the most effective means of slowing the decline of lung function associated with chronic obstructive pulmonary disease (COPD). While effective smoking cessation treatments are available, they are underutilized and nearly half of people with COPD continue to smoke. By addressing both nicotine and behavioral dependence, electronic cigarettes (EC) could help people with COPD reduce the harm of combustible cigarettes (CC) through reductions in number of Cigarettes per Day (CPD) or quitting CC completely. The purpose of this pilot study is to identify barriers and facilitators to the use of and assess the preliminary effectiveness of EC as a harm reduction strategy among people with COPD.MethodsIn an open-label two-arm randomized controlled trial pilot study, 60 patients identified as smokers with a COPD diagnosis via electronic health records from a large urban health center are randomized in a 1:1 ratio to either standard care [counseling + nicotine replacement therapy (NRT)] or counseling + EC. The NRT arm will receive nicotine patches and nicotine lozenges for 12 weeks. The EC arm will receive EC for 12 weeks. Both cohorts will receive counseling from a licensed mental health counselor. Using ecological momentary assessment, participants will report their use of CC in both arms and EC use in the EC arm daily via text message. Primary outcomes will be feasibility and acceptability of intervention, and secondary outcomes will be reduction in CPD and change in COPD symptoms as measured by COPD Assessment Tool (CAT) score at 12-weeks. EC displacement of CC. To explore attitudes towards the use of EC as a harm-reduction strategy for patients with COPD, interviews will be performed with a sample of participants from both study arms.DiscussionDespite decades of availability of smoking cessation medications, nearly half of people with COPD still smoke. This study aims to address the unmet need for feasible and effective strategies for reducing CC use among those with COPD, which has the potential to significantly improve the health of people with COPD who smoke.Trial RegistrationClinicalTrials.gov Identifier: NCT04465318.
Factors affecting test anxiety: a qualitative analysis of medical students’ views
Authors: Wadi Majed , Yusoff Muhamad Saiful Bahri , Abdul Rahim Ahmad Fuad , Lah Nik Ahmad Zuky Nik 
Published: January 2022

Abstract
Background
Medical students are vulnerable to test anxiety (TA), which impacts their professional lives and jeopardizes the optimal health care of their patients. The qualitative exploration of TA among medical students is crucial to understanding the problem. Hence, this study examined medical students’ insights into TA and their suggestions on how to reduce it.

Methods
We conducted a phenomenological study on medical students at a public university. We utilized focus group discussions (FGDs) to investigate their experiences of TA. The FGDs were transcribed verbatim, and these transcripts were analyzed using Atlas.ti software. The thematic analysis followed the recommended guidelines.

Results
Seven FGD sessions were conducted with 45 students. Three major themes emerged: the students, their academic resources, and the examiner. Each theme comprised mutually exclusive subthemes. The “students” theme was divided into negative vs. positive thoughts and self-negligence vs. self-care, “academic recources” into heavy curriculum vs. facilitative curricular aids, and “examiner” into criticism vs. feedback and strict vs. kind approaches.

Conclusion
This study provides a solid foundation for policymakers and decision makers in medical education to improve current assessment practices and student well-being. Medical students will be able to significantly alter and reduce TA if they are provided with additional psychological support and their examiners are trained on how to deal with examinees.
A comparative study: rural versus urban children as regard exposure to organophosphorus pesticides using cholinesterase enzyme activity
Authors: Mohamed Yasmen A. , Meabed Mohamed Hussien , Abougaba Khadiga Mohamed , Sayed Fatma Ali , Welson Nermeen N. , Ibrahim Raghda Ebaid 
Published: January 2022

Abstract
Background
The uncontrolled long-term exposure to organophosphorus (OP) pesticides is hazardous to health especially in children. The present study aimed to determine the acetyl cholinesterase enzyme serum level in exposure and non-exposure children groups, to explore other clinical and laboratory outcomes of organophosphorus pesticides exposure on children living in rural versus urban areas, and to establish the hemotoxic alterations as a result of the exposure. A ninety clinically free children—forty-five from rural areas and forty-five children from urban areas—were assessed, and the clinical and laboratory effects of their exposure to organophosphorus pesticides were evaluated via measuring acetyl cholinesterase (AChE) enzyme activity.

Results
Significant differences between the two areas of residence were found in weight %, visits to the field, eating vegetables without washing, presence of insecticides at home, and previous organophosphorus pesticides toxicity of the patients and their families. Eye, respiratory, cardiac, nervous, muscle, gastrointestinal, and urinary symptoms were more common in the rural residence group which shows more exposure to pesticides. The mean level of the AChE enzyme was less in the rural residence group than the other one, and it showed significant correlations with the anemia indicating parameters. A weak positive correlation was found with platelets count.

Conclusions
Chronic organophosphorus toxicity that is more prevalent in rural areas may result in many transient neglected symptoms, unrevealed acetyl cholinesterase (AChE) enzyme deficiency, anemia, and thrombocytopenia. Acetyl cholinesterase enzyme serum level can be used as a screening test for organophosphorus pesticides exposure.
Polygenic Ara-C Response Score Identifies Pediatric Patients With Acute Myeloid Leukemia in Need of Chemotherapy Augmentation
Authors: Elsayed Abdelrahman H. , Cao Xueyuan , Mitra Amit K. , Wu Huiyun , Raimondi Susana , Cogle Christopher , Al-Mansour Zeina , Ribeiro Raul C. , Gamis Alan , Kolb Edward Anders , Aplenc Richard , Alonzo Todd A. , Meshinchi Soheil , Rubnitz Jeffrey , Pounds Stanley , Lamba Jatinder K. 
Published: January 2022

PURPOSE To establish a patient-specific polygenic score derived from cytarabine (ara-C) pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment. MATERIALS AND METHODS Single nucleotide polymorphisms (SNPs) in the ara-C-pathway genes were analyzed with outcome in patients from the multicenter-AML02 trial (N = 166). Multi-SNP predictor modeling was used to develop 10-SNP Ara-C_SNP score (ACS10) using top SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02-cohort and four SNPs previously associated with ara-C triphosphate levels in the AML97 trial. ACS10 was evaluated for association with outcomes in each clinical trial arms: the standard low-dose ara-C (LDAC, n = 91) and augmented high-dose ara-C (HDAC, n = 75) arms of AML02 and the standard Ara-C, daunorubicin and etoposide (ADE) (n = 465) and the augmented ADE + gemtuzumab ozogamicin (GO; n = 466) arms of AAML0531 trial. RESULTS In the standard LDAC-arm of AML02 cohort, the low-ACS10 score group (≤ 0) had significantly worse EFS (ACS10 low v high hazard ratio [HR] = 2.81; 95% CI, 1.45 to 5.43; P = .002) and overall survival (OS; HR = 2.98; 95% CI, 1.32 to 6.75; P = .009) compared with the high-ACS10 group (score > 0). These results were validated in the standard-ADE arm of AAML0531, with poor outcome in the low-ASC10 group compared with the high-ACS10 group (EFS: HR = 1.35, 95% CI, 1.04 to 1.75, P = .026; OS: HR = 1.64, 95% CI, 1.2 to 2.22, P = .002). Within the augmented arms (AML02-HDAC and AAML0531-ADE + GO), EFS and OS did not differ between low- and high-ACS10 score groups. In both cohorts, patients with low-ACS10 consistently showed a 10-percentage point improvement in 5-year EFS with augmented therapy (AML02-HDAC or AAML0531-ADE + GO arms) than with standard therapy (AML02-LDAC or AAML0531-ADE arms). CONCLUSION Patients with low-ACS10 score experienced significantly poor outcome when treated on standard regimen. Augmentation with either high-dose ara-C or GO addition improved outcome in low-ACS10 group. A polygenic ACS10 score can identify patients with unfavorable pharmacogenetic characteristics and offers a potential for an elective augmented therapy option.
Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals
Authors: Campbell Kristin L. , Cormie Prue , Weller Sarah , Alibhai Shabbir M. H. , Bolam Kate A. , Campbell Anna , Cheville Andrea L. , Dalzell Mary-Ann , Hart Nicolas H. , Higano Celestia S. , Lane Kirstin , Mansfield Sami , McNeely Margaret L. , Newton Robert U. , Quist Morten , Rauw Jennifer , Rosenberger Friederike , Santa Mina Daniel , Schmitz Kathryn H. , Winters-Stone Kerri M. , Wiskemann Joachim , Goulart Jennifer 
Published: January 2022

PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.
Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine
Authors: Charo Lindsey M. , Eskander Ramez N. , Sicklick Jason , Kim Ki Hwan , Lim Hyo Jeong , Okamura Ryosuke , Lee Suzanna , Subramanian Rupa , Schwab Richard , Shatsky Rebecca , Plaxe Steven , Kato Shumei , Kurzrock Razelle 
Published: January 2022

PURPOSE Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.
Discontinuous gas exchange in Madagascar hissing cockroaches is not a consequence of hysteresis around a fixed PCO2 threshold
Authors: Rowe Tormod T. C. , Gutbrod Martin S. , Matthews Philip G. D. 
Published: January 2022

ABSTRACT
It has been hypothesised that insects display discontinuous gas-exchange cycles (DGCs) as a result of hysteresis in their ventilatory control, where CO2-sensitive respiratory chemoreceptors respond to changes in haemolymph PCO2 only after some delay. If correct, DGCs would be a manifestation of an unstable feedback loop between chemoreceptors and ventilation, causing PCO2 to oscillate around some fixed threshold value: PCO2 above this ventilatory threshold would stimulate excessive hyperventilation, driving PCO2 below the threshold and causing a subsequent apnoea. This hypothesis was tested by implanting micro-optodes into the haemocoel of Madagascar hissing cockroaches and measuring haemolymph PO2 and PCO2 simultaneously during continuous and discontinuous gas exchange. The mean haemolymph PCO2 of 1.9 kPa measured during continuous gas exchange was assumed to represent the threshold level stimulating ventilation, and this was compared with PCO2 levels recorded during DGCs elicited by decapitation. Cockroaches were also exposed to hypoxic (PO2 10 kPa) and hypercapnic (PCO2 2 kPa) gas mixtures to manipulate haemolymph PO2 and PCO2. Decapitated cockroaches maintained DGCs even when their haemolymph PCO2 was forced above or below the putative ∼2 kPa ventilation threshold, demonstrating that the characteristic oscillation between apnoea and gas exchange is not driven by a lag between changing haemolymph PCO2 and a PCO2 chemoreceptor with a fixed ventilatory threshold. However, it was observed that the gas exchange periods within the DGC were altered to enhance O2 uptake and CO2 release during hypoxia and hypercapnia exposure. This indicates that while respiratory chemoreceptors do modulate ventilatory activity in response to haemolymph gas levels, their role in initiating or terminating the gas exchange periods within the DGC remains unclear.
A heterothermic spectrum in hummingbirds
Authors: Shankar Anusha , Cisneros Isabelle N. H. , Thompson Sarah , Graham Catherine H. , Powers Donald R. 
Published: January 2022

ABSTRACT
Many endotherms use torpor, saving energy by a controlled reduction of their body temperature and metabolic rate. Some species (e.g. arctic ground squirrels, hummingbirds) enter deep torpor, dropping their body temperature by 23–37°C, while others can only enter shallow torpor (e.g. pigeons, 3–10°C reduction). However, deep torpor in mammals can increase predation risk (unless animals are in burrows or caves), inhibit immune function and result in sleep deprivation, so even for species that can enter deep torpor, facultative shallow torpor might help balance energy savings with these potential costs. Deep torpor occurs in three avian orders, but the trade-offs of deep torpor in birds are unknown. Although the literature hints that some bird species (mousebirds and perhaps hummingbirds) can use both shallow and deep torpor, little empirical evidence of such an avian heterothermy spectrum within species exists. We infrared imaged three hummingbird species that are known to use deep torpor, under natural temperature and light cycles, to test whether they were also capable of shallow torpor. All three species used both deep and shallow torpor, often on the same night. Depending on the species, they used shallow torpor for 5–35% of the night. The presence of a heterothermic spectrum in these bird species indicates a capacity for fine-scale physiological and genetic regulation of avian torpid metabolism.