bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of yogic breathing with perceived stress and conception of strengths and difficulties in teenagers
Authors: Kanchibhotla Divya , Subramanian Saumya , Kaushik Bharti 
Published: February 2021

Background: Mental health problems are increasing at an alarming rate throughout the world, and teenagers are no exception. They experience high levels of stress in their formative years which often leads to poor social behavior. In the present study, we examine the effect of Sudarshan Kriya Yoga (SKY), a yogic breathing technique on perceived stress and social behavior of school going teenagers. Method: A cross-sectional survey was conducted. Teenagers who practiced SKY daily constituted the study group and teenagers who did not practice any form of yoga or meditation formed the control group. Child Perceived Stress scale (C-PSS) and Strength and Difficulty questionnaire (SDQ) were used to evaluate the mental health and social behavior of both groups. Results: Lower stress scores were observed among students who practiced SKY compared to their peers. A significant difference was observed between the groups with respect to emotional problems, conduct problems, peer problems, and pro-social behavior. Gender wise comparison highlighted that the females from the SKY group scored lower on emotional problems sub-scale compared to their counterparts from control group. Results also highlighted an improved peer to peer interaction among both boys and girls in the SKY group. Conclusion: The results indicate the practice of SKY is associated with reduced stress, improved self-awareness, and social behavior.
Camouflaging in an everyday social context: An interpersonal recall study
Authors: Cook Julia , Crane Laura , Bourne Laura , Hull Laura , Mandy William 
Published: February 2021

Camouflaging is a social phenomenon operating within everyday social interactions of autistic and non-autistic people. The current study explored autistic adults’ camouflaging in an everyday social context via interpersonal process recall methodology (Kegan, 1969). A total of 17 autistic adults (8 females, 6 males and 3 agender/gender-neutral individuals) participated in a 10-min controlled social task designed to replicate a common day-to-day social situation. Participants then watched a video of their interaction with a researcher, actively identifying instances of camouflaging and discussing their experiences of camouflaging. Using thematic analysis, four themes were generated: (1) a strong desire for, yet uncertainty in, securing social acceptance and connection; (2) camouflaging, developed over time, as a means to achieve social acceptance and connection; (3) experiencing intrapersonal and interpersonal camouflaging consequences during social interactions; and (4) authentic socialising as an alternative to camouflaging. These findings are discussed with reference to the existing literature on stigma management outside the field of autism. Lay abstract Many autistic people report that, despite personal costs, they use strategies to hide their autistic characteristics or appear non-autistic at work, school or university, when speaking with health professionals, or while socialising with certain friends and family members. These strategies are often referred to as camouflaging. This study explores camouflaging during everyday social interactions. A total of 17 autistic adults were filmed taking part in a common everyday social situation – a conversation with a stranger. They then watched the video of this conversation with a researcher and answered questions about camouflaging. These autistic people told us that they (1) had a strong desire to socialise with and be valued by other people but, because of negative past experiences, they often felt unsure about their ability to do so; (2) used camouflaging to help them to socialise and be valued by others; (3) experienced negative consequences when camouflaging (e.g. fatigue, anxiety and difficulties in friendships); and (4) sometimes socialised in more autistic ways instead of camouflaging. This study shows us how autistic people often change their behaviour because of the way they are treated by nonautistic people and that autistic people may benefit from programmes that help them to socialise in more authentically autistic ways, but only if their autistic social behaviour is met with understanding and acceptance from non-autistic people.
Paternal prescription medication before conception: A retrospective cohort study of all births in Denmark 1997–2017
Authors: Wensink M.J. , Rizzi S. , Jensen T.K. , Skakkebaek N.E. , Lu Y. , Lindahl-Jacobsen R. , Eisenberg M.L. 
Published: February 2021

Aim: To study what medication fathers are being prescribed in the months preceding conception. Methods: A retrospective cohort study of Danish national registries, comprising all births in Denmark 1997–2017 (1.3 million births). Time trends and absolute levels of paternal prescription medication in the 6 months prior to conception were assessed. While all medications were examined ( N = 1335), we focused on the main medication groups, medications that have increased in use over time, and medications for which previous evidence exists of an effect on sperm quality. Results: The average number of prescriptions increased over the study period (from 0.75 prescriptions to 0.82 per birth). Polypharmacy (three or more prescriptions) increased from less than 8% to 10% of fathers. The use of pain medication, proton-pump inhibitors, selective serotonin reuptake inhibitors and some inhalants have all increased markedly over the last 20 years. Conclusions: Potential harm to the offspring done by paternal medication may present an increasing problem. As paternal medication exposure is increasing, examination of generational effects, such as major birth defects, is necessary.
Increase in sickness absence due to mental disorders in Finland: trends by gender, age and diagnostic group in 2005–2019
Authors: Blomgren Jenni , Perhoniemi Riku 
Published: February 2021

Aims: Mental disorders are among the key public health challenges and cause a significant share of sickness absence. The aim of this study was to examine gender and age-specific trends in sickness absence in Finland among non-retired persons aged 16–67 years during 2005–2019 by main diagnostic groups. Special focus was put on the development of sickness absence due to mental and behavioural disorders. Methods: Data on compensated sickness allowance days were retrieved from the database of the Social Insurance Institution of Finland, and data on the non-retired population aged 16–67 years from the database of Statistics Finland for years 2005–2019. Yearly age-standardised sickness absence rates (yearly sickness absence days per each person in the population at risk) according to diagnostic group were calculated for women and men in age groups 16–34, 35–49 and 50–67 years. Results: A steep increase in sickness absence due to mental disorders was observed between 2016 and 2019 in all age groups among both genders, but the increase was more prominent among women. The age group 16–34 years also showed a longer-term gradual increase. In all examined gender and age groups, the increase was mainly a consequence of an increase in sickness absence due to depression and anxiety disorders. Conclusions: Increase in sickness absence due to mental disorders is an early sign of threats to work ability and productivity of the working-age population. Several factors may simultaneously drive the development. The specific reasons for the recent trend need to be studied.
Effect of sotagliflozin as an adjunct to insulin therapy on blood pressure and arterial stiffness in adults with type 1 diabetes: A post hoc pooled analysis of inTandem1 and inTandem2
Authors: Rodbard Helena W , Giaccari Andrea , Cariou Bertrand , Garg Satish , Davies Michael J , Seth Kiernan , Sawhney Sangeeta 
Published: February 2021

Objective: Evaluate the effect of sotagliflozin, a dual inhibitor of sodium glucose cotransporter (SGLT) 1 and 2, on arterial stiffness in patients with type 1 diabetes (T1D) treated with sotagliflozin as adjunct to optimized insulin therapy. Methods: In this post hoc analysis, indirect markers of arterial stiffness, including pulse pressure, mean arterial pressure (MAP), and double product, were calculated using observed systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at 24 weeks using data from a pooled patient population from the inTandem1 and inTandem2 randomized controlled trials ( n = 1575). Results: Baseline characteristics were similar among groups. Relative to placebo at Week 24, sotagliflozin 200 mg and 400 mg reduced SBP by 2.03 mm Hg (95% CI −3.30 to −0.75; p = 0.0019) and 2.85 mm Hg (−4.12 to −1.57; p < 0.0001), respectively. DBP decreased by 1.1 and 0.9 mm Hg, MAP by 1.4 and 1.6 mm Hg, and double product by 202.5 and 221.1 bpm × mm Hg, respectively ( p < 0.05 for all). No increases in heart rate were observed. Conclusion: In adults with T1D, adding sotagliflozin to insulin significantly reduced blood pressure and other markers of arterial stiffness and vascular resistance.
BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia
Authors: Herbaux Charles , Kornauth Christoph , Poulain Stéphanie , Chong Stephen J. F. , Collins Mary C. , Valentin Rebecca , Hackett Liam , Tournilhac Olivier , Lemonnier François , Dupuis Jehan , Daniel Adrien , Tomowiak Cecile , Laribi Kamel , Renaud Loïc , Roos-Weil Damien , Rossi Cedric , Van Den Neste Eric , Leyronnas Cecile , Merabet Fatiha , Malfuson Jean Valère , Tiab Mourad , Ysebaert Loïc , Ng Samuel , Morschhauser Franck , Staber Philipp B. , Davids Matthew S. 
Published: February 2021

Abstract
Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab, have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell receptor pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this disease. Twenty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis (priming) and the relative dependence of a cell on different antiapoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis and predominantly depended on BCL-2 and MCL-1 proteins for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting the JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib. We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease. Our functional, precision-medicine–based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting a clinical exploration of such combinations in T-PLL.
Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin
Authors: Schmalbrock Laura K. , Dolnik Anna , Cocciardi Sibylle , Sträng Eric , Theis Frauke , Jahn Nikolaus , Panina Ekaterina , Blätte Tamara J. , Herzig Julia , Skambraks Sabrina , Rücker Frank G. , Gaidzik Verena I. , Paschka Peter , Fiedler Walter , Salih Helmut R. , Wulf Gerald , Schroeder Thomas , Lübbert Michael , Schlenk Richard F. , Thol Felicitas , Heuser Michael , Larson Richard A. , Ganser Arnold , Stunnenberg Hendrik G. , Minucci Saverio , Stone Richard M. , Bloomfield Clara D. , Döhner Hartmut , Döhner Konstanze , Bullinger Lars 
Published: February 2021

Abstract
In the international randomized phase 3 RATIFY (Randomized AML Trial In FLT3 in patients less than 60 Years old) trial, the multikinase inhibitor midostaurin significantly improved overall and event-free survival in patients 18 to 59 years of age with FLT3-mutated acute myeloid leukemia (AML). However, only 59% of patients in the midostaurin arm achieved protocol-specified complete remission (CR), and almost half of patients achieving CR relapsed. To explore underlying mechanisms of resistance, we studied patterns of clonal evolution in patients with FLT3-internal tandem duplications (ITD)-positive AML who were entered in the RATIFY or German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and received treatment with midostaurin. To this end, paired samples from 54 patients obtained at time of diagnosis and at time of either relapsed or refractory disease were analyzed using conventional Genescan-based testing for FLT3-ITD and whole exome sequencing. At the time of disease resistance or progression, almost half of the patients (46%) became FLT3-ITD negative but acquired mutations in signaling pathways (eg, MAPK), thereby providing a new proliferative advantage. In cases with FLT3-ITD persistence, the selection of resistant ITD clones was found in 11% as potential drivers of disease. In 32% of cases, no FLT3-ITD mutational change was observed, suggesting either resistance mechanisms bypassing FLT3 inhibition or loss of midostaurin inhibitory activity because of inadequate drug levels. In summary, our study provides novel insights into the clonal evolution and resistance mechanisms of FLT3-ITD–mutated AML under treatment with midostaurin in combination with intensive chemotherapy.
Time dependent effect of cold ischemia on the phosphoproteome and protein kinase activity in fresh-frozen colorectal cancer tissue obtained from patients
Authors: Buffart Tineke E. , van den Oord Rosanne A. H. M. , van den Berg Adriënne , Hilhorst Riet , Bastiaensen Niek , Pruijt Hans F. M. , van den Brule Adriaan , Nooijen Peet , Labots Mariette , de Goeij-de Haas Richard R. , Dekker Henk , Piersma Sander R. , Pham Thang V. , van der Leij Theo , de Wijn Rik , Ruijtenbeek Rob , Jiménez Connie R. , Verheul Henk M. W. 
Published: February 2021

Abstract
Background
Based on their potential to analyze aberrant cellular signaling in relation to biological function, kinase activity profiling in tumor biopsies by peptide microarrays and mass spectrometry-based phosphoproteomics may guide selection of protein kinase inhibitors in patients with cancer. Variable tissue handling procedures in clinical practice may influence protein phosphorylation status and kinase activity and therewith may hamper biomarker discovery. Here, the effect of cold ischemia time (CIT) on the stability of kinase activity and protein phosphorylation status in fresh-frozen clinical tissue samples was studied using peptide microarrays and mass spectrometry-based phosphoproteomics.

Methods
Biopsies of colorectal cancer resection specimens from five patients were collected and snap frozen immediately after surgery and at 6 additional time points between 0 and 180 min of CIT. Kinase activity profiling was performed for all samples using a peptide microarray. MS-based global phosphoproteomics was performed in tumors from 3 patients at 4 time points. Statistical and cluster analyses were performed to analyze changes in kinase activity and phosphoproteome resulting from CIT.

Results
Unsupervised cluster analysis of kinase activity and phosphoproteome data revealed that samples from the same patients cluster together. Continuous ANOVA analysis of all 7 time points for 5 patient samples resulted in 4 peptides out of 210 (2%) with significantly (p < 0.01 and fold change > 2) altered signal intensity in time. In 4 out of 5 patients tumor kinase activity was stable with CIT. MS-based phosphoproteomics resulted in the detection of 10,488 different phosphopeptides with on average 6044 phosphopeptides per tumor sample. 2715 phosphopeptides were detected in all samples at time point 0, of which 90 (3.3%) phosphopeptides showed significant changes in intensity with CIT (p < 0.01). Only two phosphopeptides were significantly changed in all time points, including one peptide (PKP3) with a fold change > 2.

Conclusions
The vast majority of the phosphoproteome as well as the activity of protein kinases in colorectal cancer resection tissue is stable up to 180 min of CIT and reflects tumor characteristics. However, specific changes in kinase activity with increasing CIT were observed. Therefore, stringent tissue collection procedures are advised to minimize changes in kinase activity during CIT.
Global point-of-care ultrasound education and training in the age of COVID-19
Authors: Eke Onyinyechi F. , Henwood Patricia C. , Wanjiku Grace W. , Fasina Abiola , Kharasch Sigmund J. , Shokoohi Hamid 
Published: February 2021

AbstractThe COVID-19 pandemic has disrupted traditional global point-of-care ultrasound (POCUS) education and training, as a result of travel restrictions. It has also provided an opportunity for innovation using a virtual platform. Tele-ultrasound and video-conferencing are alternative and supportive tools to augment global POCUS education and training. There is a need to support learners and experts to ensure that maximum benefit is gained from the use of these innovative modalities.
FiNGS: high quality somatic mutations using filters for next generation sequencing
Authors: Wardell Christopher Paul , Ashby Cody , Bauer Michael Anton 
Published: February 2021

Abstract
Background
Somatic variant callers are used to find mutations in sequencing data from cancer samples. They are very sensitive and have high recall, but also may produce low precision data with a large proportion of false positives. Further ad hoc filtering is commonly performed after variant calling and before further analysis. Improving the filtering of somatic variants in a reproducible way represents an unmet need. We have developed Filters for Next Generation Sequencing (FiNGS), software written specifically to address these filtering issues.

Results
Developed and tested using publicly available sequencing data sets, we demonstrate that FiNGS reliably improves upon the precision of default variant caller outputs and performs better than other tools designed for the same task.

Conclusions
FiNGS provides researchers with a tool to reproducibly filter somatic variants that is simple to both deploy and use, with filters and thresholds that are fully configurable by the user. It ingests and emits standard variant call format (VCF) files and will slot into existing sequencing pipelines. It allows users to develop and implement their own filtering strategies and simple sharing of these with others.
MeltingPlot, a user-friendly online tool for epidemiological investigation using High Resolution Melting data
Authors: Perini Matteo , Batisti Biffignandi Gherard , Di Carlo Domenico , Pasala Ajay Ratan , Piazza Aurora , Panelli Simona , Zuccotti Gian Vincenzo , Comandatore Francesco 
Published: February 2021

Abstract
Background
The rapid identification of pathogen clones is pivotal for effective epidemiological control strategies in hospital settings. High Resolution Melting (HRM) is a molecular biology technique suitable for fast and inexpensive pathogen typing protocols. Unfortunately, the mathematical/informatics skills required to analyse HRM data for pathogen typing likely limit the application of this promising technique in hospital settings.

Results
MeltingPlot is the first tool specifically designed for epidemiological investigations using HRM data, easing the application of HRM typing to large real-time surveillance and rapid outbreak reconstructions. MeltingPlot implements a graph-based algorithm designed to discriminate pathogen clones on the basis of HRM data, producing portable typing results. The tool also merges typing information with isolates and patients metadata to create graphical and tabular outputs useful in epidemiological investigations and it runs in a few seconds even with hundreds of isolates. Availability: https://skynet.unimi.it/index.php/tools/meltingplot/.

Conclusions
The analysis and result interpretation of HRM typing protocols can be not trivial and this likely limited its application in hospital settings. MeltingPlot is a web tool designed to help the user to reconstruct epidemiological events by combining HRM-based clustering methods and the isolate/patient metadata. The tool can be used for the implementation of HRM based real time large scale surveillance programs in hospital settings.
A simple method to estimate the in-house limit of detection for genetic mutations with low allele frequencies in whole-exome sequencing analysis by next-generation sequencing
Authors: Miura Takumi , Yasuda Satoshi , Sato Yoji 
Published: February 2021

Abstract
Background
Next-generation sequencing (NGS) has profoundly changed the approach to genetic/genomic research. Particularly, the clinical utility of NGS in detecting mutations associated with disease risk has contributed to the development of effective therapeutic strategies. Recently, comprehensive analysis of somatic genetic mutations by NGS has also been used as a new approach for controlling the quality of cell substrates for manufacturing biopharmaceuticals. However, the quality evaluation of cell substrates by NGS largely depends on the limit of detection (LOD) for rare somatic mutations. The purpose of this study was to develop a simple method for evaluating the ability of whole-exome sequencing (WES) by NGS to detect mutations with low allele frequency. To estimate the LOD of WES for low-frequency somatic mutations, we repeatedly and independently performed WES of a reference genomic DNA using the same NGS platform and assay design. LOD was defined as the allele frequency with a relative standard deviation (RSD) value of 30% and was estimated by a moving average curve of the relation between RSD and allele frequency.

Results
Allele frequencies of 20 mutations in the reference material that had been pre-validated by droplet digital PCR (ddPCR) were obtained from 5, 15, 30, or 40 G base pair (Gbp) sequencing data per run. There was a significant association between the allele frequencies measured by WES and those pre-validated by ddPCR, whose p-value decreased as the sequencing data size increased. By this method, the LOD of allele frequency in WES with the sequencing data of 15 Gbp or more was estimated to be between 5 and 10%.

Conclusions
For properly interpreting the WES data of somatic genetic mutations, it is necessary to have a cutoff threshold of low allele frequencies. The in-house LOD estimated by the simple method shown in this study provides a rationale for setting the cutoff.