bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACE2 and TMPRSS2 SARS-CoV-2 infectivity genes: deep mutational scanning and characterization of missense variants
Authors: Zhang Lingxin , Sarangi Vivekananda , Liu Duan , Ho Ming-Fen , Grassi Angela R , Wei Lixuan , Moon Irene , Vierkant Robert A , Larson Nicholas B , Lazaridis Konstantinos N , Athreya Arjun P , Wang Liewei , Weinshilboum Richard 
Published: July 2022

Abstract
The human angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) proteins play key roles in the cellular internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the coronavirus disease of 2019 (COVID-19) pandemic. We set out to functionally characterize the ACE2 and TMPRSS2 protein abundance for variant alleles encoding these proteins that contained non-synonymous single-nucleotide polymorphisms (nsSNPs) in their open reading frames (ORFs). Specifically, a high-throughput assay, deep mutational scanning (DMS), was employed to test the functional implications of nsSNPs, which are variants of uncertain significance in these two genes. Specifically, we used a ‘landing pad’ system designed to quantify the protein expression for 433 nsSNPs that have been observed in the ACE2 and TMPRSS2 ORFs and found that 8 of 127 ACE2, 19 of 157 TMPRSS2 isoform 1 and 13 of 149 TMPRSS2 isoform 2 variant proteins displayed less than ~25% of the wild-type protein expression, whereas 4 ACE2 variants displayed 25% or greater increases in protein expression. As a result, we concluded that nsSNPs in genes encoding ACE2 and TMPRSS2 might potentially influence SARS-CoV-2 infectivity. These results can now be applied to DNA sequence data for patients infected with SARS-CoV-2 to determine the possible impact of patient-based DNA sequence variation on the clinical course of SARS-CoV-2 infection.
Natural history of KBG syndrome in a large European cohort
Authors: Loberti Lorenzo , Bruno Lucia Pia , Granata Stefania , Doddato Gabriella , Resciniti Sara , Fava Francesca , Carullo Michele , Rahikkala Elisa , Jouret Guillaume , Menke Leonie A , Lederer Damien , Vrielynck Pascal , Ryba Lukáš , Brunetti-Pierri Nicola , Lasa-Aranzasti Amaia , Cueto-González Anna Maria , Trujillano Laura , Valenzuela Irene , Tizzano Eduardo F , Spinelli Alessandro Mauro , Bruno Irene , Currò Aurora , Stanzial Franco , Benedicenti Francesco , Lopergolo Diego , Santorelli Filippo Maria , Aristidou Constantia , Tanteles George A , Maystadt Isabelle , Tkemaladze Tinatin , Reimand Tiia , Lokke Helen , Õunap Katrin , Haanpää Maria K , Holubová Andrea , Zoubková Veronika , Schwarz Martin , Žordania Riina , Muru Kai , Roht Laura , Tihveräinen Annika , Teek Rita , Thomson Ulvi , Atallah Isis , Superti-Furga Andrea , Buoni Sabrina , Canitano Roberto , Scandurra Valeria , Rossetti Annalisa , Grosso Salvatore , Battini Roberta , Baldassarri Margherita , Mencarelli Maria Antonietta , Rizzo Caterina Lo , Bruttini Mirella , Mari Francesca , Ariani Francesca , Renieri Alessandra , Pinto Anna Maria 
Published: July 2022

Abstract
KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: −0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.
Why Do Military Officers Condone Sexual Violence? A General Theory of Commander Tolerance
Authors: Ju Changwook 
Published: July 2022

AbstractWhy do commanders tolerate sexual violence by their subordinates? Commander tolerance allows military sexual violence (MSV) to persist in times of peace, war, and post-conflict peacekeeping. However, most of the previous studies on MSV have focused on perpetrators’ criminal motives while neglecting the role of commander tolerance. In this article, I offer a tripartite general theory of commander tolerance that systematically weaves together the diverse conditions under which commanders tolerate MSV at the micro, meso, and macro levels of social scientific inquiry. Toward this end, I build on the conventional principal–agent model of MSV but crucially depart from its core constructs to create a dynamic multi-commander theoretical framework. The theory represents the most rigorous explanation of commander tolerance to date and offers practical implications for military justice systems in terms of MSV. Placing commander tolerance at the center of studies on military violence opens an array of new avenues for research.
Development and Validation of a DLLME–GC–MS-MS Method for the Determination of Benzotriazole UV Stabilizer UV-327 and Its Metabolites in Human Blood
Authors: Fischer Corinna , Göen Thomas 
Published: July 2022

Abstract2-(5-Chloro-benzotriazol-2-yl)-4,6-di-(tert-butyl)phenol (UV-327) is used as an ultraviolet (UV) absorber in plastic materials and coatings. To investigate its metabolism and to assess human exposure, analytical methods are necessary for the determination of UV-327 and its metabolites in human biological specimens. The method thus presented targets the determination of UV-327 and several of its predicted metabolites in blood using protein precipitation, dispersive liquid–liquid microextraction (DLLME) and derivatization. The trimethylsilylated analytes and internal standards are separated by gas chromatography and analyzed with tandem mass spectrometry. The DLLME procedure was optimized with respect to the type and volume of disperser and extraction solvents, the pH value of the sample solution and the addition of salt. During method development, an effective ex vivo lactone/hydroxyl carboxylic acid interconversion was observed for two metabolites, each containing a carboxyl group adjacent to the phenolic hydroxyl group. The analytes resulting from interconversion enabled a more sensitive and reliable determination of the metabolites compared to their native structures. Method validation revealed limits of detection between 0.02 and 0.36 µg/L. The mean relative recovery rates ranged from 91% to 118%. Precision and repeatability were demonstrated by relative standard deviations in the range of 0.6–14.2% and 1.1–13.7%, respectively. The presently described procedure enables the sensitive and robust analysis of UV-327 and its metabolites in human blood and allows the elucidation of the human UV-327 metabolism as well as the assessment of exposure in potentially exposed individuals.
Practical management of older adults with cancer: geriatric oncology in Japan
Authors: Mizutani Tomonori 
Published: July 2022

Abstract
Japan has the highest proportion of older adults globally, and the average life expectancy of the Japanese population has increased in recent decades. Given that the incidence of cancer increases with age, it is a major health concern for older adults. However, geriatric oncology is a relatively new field and collaboration between oncologists and geriatricians in Japan is limited. Hence, oncologists and other healthcare professionals engaged in cancer care have not been able to adequately understand geriatric care, and information and experience are insufficient for this specific population. Thus, they may struggle with the assessment and management of older adults with cancer. Recently, several Japanese academic societies for cancer have developed practical guidelines and research policy with regard to geriatric research in older adults with cancer, in addition to organizing symposia and workshops focusing especially on geriatric oncology. Furthermore, because the Japan Geriatrics Society established a discipline committee on cancer, close collaboration between oncologists and geriatricians has grown steadily. Geriatric oncology is currently recognized as an important field of cancer care in Japan. The integration of oncology and geriatric care is anticipated in the near future. However, understanding the aspects of geriatric care and meanings of technical jargons used in geriatric oncology is difficult. Accordingly, this article provides an overview of the current knowledge and recent advancements in geriatric oncology. In addition, it outlines the current status and problems of geriatric oncology in Japan.
‘THIS IS NO COUNTRY FOR OLD (WO)MEN’? AN EXAMINATION OF THE APPROACH TAKEN TO CARE HOME RESIDENTS DURING THE COVID-19 PANDEMIC
Authors: Ó Néill Clayton 
Published: July 2022

ABSTRACT
This article discusses the human rights of residents in care homes in England who were affected by restrictions that were imposed during the first months of the COVID-19 pandemic in order to safeguard health and life at a time of public health emergency. It focuses on the potentially adversarial relationship between the need to protect the health of these residents and the possible adverse interferences with their human rights in the initial phase of the pandemic. The scope and application of these rights to the healthcare context is not straightforward due to the exigencies of the pandemic. Consideration is given to whether their rights, as protected by the European Convention on Human Rights (ECHR) and the United Nations Convention on the Rights of Persons with Disabilities (CRPD) are vindicated or breached by the actions taken in the context of the COVID-19 pandemic. The article questions whether the restrictions that were applied were justified, given the limitations that exist within some ECHR Articles. It deliberates upon what can be done to ensure that relevant bodies and care homes, themselves, are better enabled to respond to a public health emergency in an individualistic, rights-based manner, based upon both principlism and pragmatism.
Do Ask, Do Tell: Understanding Disclosure of Sexuality and Implications Among MSM Active Duty Service Members
Authors: Staten M Colten , Webster Alicia , Carter Gregory 
Published: July 2022

ABSTRACT

Introduction
Men who have sex with men (MSM) account for over half of new diagnoses of human immunodeficiency virus (HIV) every year in the United States, with over one-third of this population being unaware of their HIV status. The U.S. Military requires biannual HIV testing for all service members. Although this may be an appropriate recommendation for the military at large, current health protection agencies suggest more frequent testing for those at increased risk of HIV transmission, such as those in the MSM community. However, more frequent testing for those at higher risk relies heavily on the preliminary step of patient disclosure of sexual practices to health care providers.

Materials and Methods
An exploratory cross-sectional study was conducted in order to gain a better understanding of the relationship between sexual health variables and the disclosure of sexual identity to health care providers by MSM service members. A convenience sample of MSM currently serving in the U.S. military services (N = 354) was used to collect demographic data, sexual health and history, and opinions concerning medical treatment and HIV. Analyses of the data were conducted using univariate analysis and multivariate regression.

Results
Men of color were more likely to report a higher degree of sexual identification transparency with their health care providers, which deviates from the civilian population. Pre-exposure prophylaxis (PrEP) uptake was increased among individuals who were more transparent with their health care providers.

Conclusions
Findings from this study indicate that feeling more comfortable sharing one’s sexual identification with a health care provider results in increased engagement with HIV prevention measures. Potential implications for the Military Health System are the advancement of preventive sexual health screening procedures and the development and revision of policies that promote positive outcomes for gender and sexual minorities.
COVID-19 anti-contagion policies and economic support measures in the USA
Authors: Dergiades Theologos , Milas Costas , Mossialos Elias , Panagiotidis Theodore 
Published: July 2022

Abstract
Current literature assumes that non-pharmaceutical interventions (NPIs) reduce COVID-19 infections uniformly, that is, irrespectively of their strength. The role of economic support measures (ESM) in controlling the virus is also overlooked. Using a panel threshold model of COVID-19 cases in the US states, we identify three distinct regimes of ‘low’, ‘medium’, and ‘high’ severity interventions; the latter being more effective towards reducing infections growth. ESM increase the efficacy of NPIs through a behavioural channel that lowers the workplace hours supplied by individuals. Nonetheless, when containment policies are not very stringent (‘low’ regime) or are too draconian (‘high’ regime), ESM are less effective towards suppressing the pandemic. Finally, we find that the largest impact towards reducing the growth of infections comes jointly from school closures, workplace closures, cancelation of public events, and restrictions on internal movement, followed by the stay-at-home requirements, and the closure of public transport.
DNA hypermethylation promotes the flowering of orchardgrass during vernalization
Authors: Yang Zhongfu , Yan Haidong , Wang Jianping , Nie Gang , Feng Guangyan , Xu Xiaoheng , Li Dandan , Huang Linkai , Zhang Xinquan 
Published: July 2022

Abstract
Vernalization, influenced by environmental factors, is an essential process associated with the productivity of temperate crops, during which epigenetic regulation of gene expression plays an important role. Although DNA methylation is one of the major epigenetic mechanisms associated with the control of gene expression, global changes in DNA methylation in the regulation of gene expression during vernalization-induced flowering of temperate plants remain largely undetermined. To characterize vernalization-associated DNA methylation dynamics, we performed whole-genome bisulfite-treated sequencing and transcriptome sequencing in orchardgrass (Dactylis glomerata) during vernalization. The results revealed that increased levels of genome DNA methylation during the early vernalization of orchardgrass were associated with transcriptional changes in DNA methyltransferase and demethylase genes. Upregulated expression of vernalization-related genes during early vernalization was attributable to an increase in mCHH in the promoter regions of these genes. Application of an exogenous DNA methylation accelerator or overexpression of orchardgrass NUCLEAR POLY(A) POLYMERASE (DgPAPS4) promoted earlier flowering, indicating that DNA hypermethylation plays an important role in vernalization-induced flowering. Collectively, our findings revealed that vernalization-induced hypermethylation is responsible for floral primordium initiation and development. These observations provide a theoretical foundation for further studies on the molecular mechanisms underlying the control of vernalization in temperate grasses.
Transcription factors ZmNF-YA1 and ZmNF-YB16 regulate plant growth and drought tolerance in maize
Authors: Yang Yaling , Wang Baomei , Wang Jiemin , He Chunmei , Zhang Dengfeng , Li Peng , Zhang Juren , Li Zhaoxia 
Published: July 2022

Abstract
The identification of drought stress regulatory genes is crucial for the genetic improvement of maize (Zea mays L.) yield. Nuclear factors Y (NF-Ys) are important transcription factors, but their roles in the drought stress tolerance of plants and underlying molecular mechanisms are largely unknown. In this work, we used yeast two-hybrid screening to identify potential interactors of ZmNF-YB16 and confirmed the interaction between ZmNF-YA1 and ZmNF-YB16-YC17 and between ZmNF-YA7 and ZmNF-YB16-YC17. ZmNF-YB16 interacted with ZmNF-YC17 via its histone fold domain to form a heterodimer in the cytoplasm and then entered the nucleus to form a heterotrimer with ZmNF-YA1 or ZmNF-YA7 under osmotic stress. Overexpression of ZmNF-YA1 improved drought and salt stress tolerance and root development of maize, whereas zmnf-ya1 mutants exhibited drought and salt stress sensitivity. ZmNF-YA1-mediated transcriptional regulation, especially in JA signaling, histone modification, and chromatin remodeling, could underlie the altered stress tolerance of zmnf-ya1 mutant plants. ZmNF-YA1 bound to promoter CCAAT motifs and directly regulated the expression of multiple genes that play important roles in stress responses and plant development. Comparison of ZmNF-YB16- and ZmNF-YA1-regulated genes showed that ZmNF-YA1 and ZmNF-YB16 have similar biological functions in stress responses but varied functions in other biological processes. Taken together, ZmNF-YA1 is a positive regulator of plant drought and salt stress responses and is involved in the root development of maize, and ZmNF-Y complexes with different subunits may have discrepant functions.
Rate and Predictors of Patients with Chronic Pain Establishing Care with Pain Psychology Following Pain Physician Referral
Authors: Lyon Ronit Y , Schuster Nathaniel M 
Published: July 2022

Abstract

Objective
To determine, among patients with chronic pain who had received pain physician referral to pain psychology, the rate of establishing care and factors related to establishing care with pain psychology.

Design
Retrospective study.

Setting
Academic tertiary care center.

Subjects
Patients from the University of California, San Diego (UCSD) Center for Pain Medicine.

Methods
This was an institutional review board–approved, retrospective study of 150 consecutive referrals of unique patients from UCSD Pain Medicine to UCSD Pain Psychology.

Results
Of 150 patients referred to pain psychology, 74 (49.3%) established care with pain psychology. Of 98 patients who had previously seen mental health services, 58 established care with pain psychology (59.2%; 95% confidence interval [CI]: 49% to 69%), whereas of 52 patients who had not previously seen mental health services, 16 established care with pain psychology (30.8%; 95% CI: 18% to 43%) (odds ratio [OR] 3.26; 95% CI: 1.60 to 6.66). In the patient subset with depression and/or anxiety, of 82 patients who had previously seen mental health services, 47 established care with pain psychology (57.3%; 95% CI: 47% to 68%), whereas of 20 patients who had not previously seen mental health services, three established care with pain psychology (15%; 95% CI: –1% to 31%) (OR 7.61; 95% CI: 2.07 to 28.01). Of 96 patients referred for general pain psychology evaluations, 43 established care (45%; 95% CI: 35% to 55%), whereas of 38 patients referred for preprocedural evaluation for an implantable device, 24 established care (63%; 95% CI: 48% to 78%).

Conclusion
Patients are significantly more likely to establish care with pain psychology if they have previously seen a mental health professional. This was even more marked among the patient subset with a history of depression and/or anxiety who had engaged in mental health services than among those with a history of depression and/or anxiety who had not engaged in mental health services. Whether referral was for general psychological evaluation or preprocedural evaluation for an implantable device did not significantly influence whether patients established care. Targeted interventions are needed to improve the likelihood of patients engaging with pain psychology services.
Autologous stem cell transplantation improves cardiopulmonary exercise testing outcomes in systemic sclerosis patients
Authors: Gadioli Leonardo Pippa , Costa-Pereira Karla , Dias Juliana B E , Moraes Daniela A , Crescêncio Júlio C , Schwartzmann Pedro V , Gallo-Júnior Lourenço , Schmidt André , Oliveira Maria Carolina 
Published: July 2022

Abstract

Objectives
Autologous haematopoietic stem cell transplantation (AHSCT) is a disease-modifying treatment for patients with severe SSc. Here, we aimed at assessing cardiopulmonary function outcomes of SSc patients after AHSCT.

Methods
Twenty-seven SSc adult patients treated with AHSCT were included in this retrospective study. Most had the diffuse cutaneous subset (93%) and pulmonary involvement (85%). Before and 12 months after AHSCT, patients underwent cardiopulmonary exercise testing, transthoracic echocardiography, pulmonary function test with diffusing capacity for carbon monoxide (DLCO), 6-min walk test (6MWT) and quality of life evaluations.

Results
After AHSCT, the peak VO2 increased from 954 to 1029 ml/min (P = 0.02), the percentage of predicted peak VO2 increased from 48.9 to 53.5 m (P = 0.01), and the distance measured by the 6MWT increased from 445 to 502 m (P = 0.01), compared with baseline. Improvements in peak VO2 correlated positively with improvements in 6MWT distance, and negatively with a decrease in resting heart rate. At baseline, patients with DLCO &gt;70% had higher peak VO2 values than those with DLCO &lt;70% (P = 0.04), but after AHSCT all patients showed improved VO2 values, regardless of baseline DLCO levels. Increases in VO2 levels after AHSCT positively correlated with increases in the physical component scores of the Short Form-36 quality of life questionnaire (r = 0.70; P = 0.0003).

Conclusion
AHSCT improves the aerobic capacity of SSc patients probably reflecting combined increments in lungs, skeletal muscle and cardiac function.