bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging pleiotropic association using sparse group variable selection in genomics data
Authors: Sutton Matthew , Sugier Pierre-Emmanuel , Truong Therese , Liquet Benoit 
Published: January 2022

Abstract
Background
Genome-wide association studies (GWAS) have identified genetic variants associated with multiple complex diseases. We can leverage this phenomenon, known as pleiotropy, to integrate multiple data sources in a joint analysis. Often integrating additional information such as gene pathway knowledge can improve statistical efficiency and biological interpretation. In this article, we propose statistical methods which incorporate both gene pathway and pleiotropy knowledge to increase statistical power and identify important risk variants affecting multiple traits.

Methods
We propose novel feature selection methods for the group variable selection in multi-task regression problem. We develop penalised likelihood methods exploiting different penalties to induce structured sparsity at a gene (or pathway) and SNP level across all studies. We implement an alternating direction method of multipliers (ADMM) algorithm for our penalised regression methods. The performance of our approaches are compared to a subset based meta analysis approach on simulated data sets. A bootstrap sampling strategy is provided to explore the stability of the penalised methods.

Results
Our methods are applied to identify potential pleiotropy in an application considering the joint analysis of thyroid and breast cancers. The methods were able to detect eleven potential pleiotropic SNPs and six pathways. A simulation study found that our method was able to detect more true signals than a popular competing method while retaining a similar false discovery rate.

Conclusion
We developed feature selection methods for jointly analysing multiple logistic regression tasks where prior grouping knowledge is available. Our method performed well on both simulation studies and when applied to a real data analysis of multiple cancers.
Remote-controlled cholangiography injection device: first clinical study in China
Authors: Chen Huan , Shan Li-yu , Ma Tao , Wang Yue , Feng Zhe , Dong Ding-Hui , Lv Yi , Zhu Hao-Yang 
Published: January 2022

AbstractBackgroundX-ray cholangiography is of great value in the imaging of biliary tract diseases; however, occupational radiation exposure is unavoidable. Moreover, clinicians must manually inject the contrast dye, which may result in a relatively high incidence of adverse reactions due to unstable injection pressure. Thus, there is a need to develop a novel remote-controlled cholangiography injection device.MethodsPatients with external biliary drainage requiring cholangiography were included. A remote-controlled injection device was developed with three major components: an injection pump, a pressure sensor, and a wireless remote-control panel. Image quality, adverse reactions, and radiation dose were evaluated.ResultsDifferent kinds of X-ray cholangiography were successfully and smoothly performed using this remote-controlled injection device in all patients. The incidence of adverse reactions in the device group was significantly lower than that in the manual group (4.17% vs. 13.9%,P = 0.001), and increasing the injection pressure increased the incidence of adverse reactions. In addition, the device helped operators avoid ionizing radiation completely.ConclusionsWith good control of injection pressure (within 10 kPa), the remote-controlled cholangiography injection device could replace the need for the doctor to inject contrast agent with good security and effectivity. It is expected to be submitted for clinical application.
A predictive model for postoperative progressive haemorrhagic injury in traumatic brain injuries
Authors: Chen Tiange , Chen Siming , Wu Yun , Chen Yilei , Wang Lei , Liu Jinfang 
Published: January 2022

Abstract
Background
Progressive haemorrhagic injury after surgery in patients with traumatic brain injury often results in poor patient outcomes. This study aimed to develop and validate a practical predictive tool that can reliably estimate the risk of postoperative progressive haemorrhagic injury (PHI) in patients with traumatic brain injury (TBI).

Methods
Data from 645 patients who underwent surgery for TBI between March 2018 and December 2020 were collected. The outcome was postoperative intracranial PHI, which was assessed on postoperative computed tomography. The least absolute shrinkage and selection operator (LASSO) regression model, univariate analysis, and Delphi method were applied to select the most relevant prognostic predictors. We combined conventional coagulation test (CCT) data, thromboelastography (TEG) variables, and several predictors to develop a predictive model using binary logistic regression and then presented the results as a nomogram. The predictive performance of the model was assessed with calibration and discrimination. Internal validation was assessed.

Results
The signature, which consisted of 11 selected features, was significantly associated with intracranial PHI (p < 0.05, for both primary and validation cohorts). Predictors in the prediction nomogram included age, S-pressure, D-pressure, pulse, temperature, reaction time, PLT, prothrombin time, activated partial thromboplastin time, FIB, and kinetics values. The model showed good discrimination, with an area under the curve of 0.8694 (95% CI, 0.8083–0.9304), and good calibration.

Conclusion
This model is based on a nomogram incorporating CCT and TEG variables, which can be conveniently derived at hospital admission. It allows determination of this individual risk for postoperative intracranial PHI and will facilitate a timely intervention to improve outcomes.
Subacute thyroiditis during early pregnancy: a case report and literature review
Authors: Bai Chao-Fang , Shen Guang-Hui , Yang Ying , Yang Ke , R Hayden Melvin , Zhou Yuan-Yuan , Geng Xing-Qian 
Published: January 2022

Abstract
Background
Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy.

Case presentation
A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41.

Conclusion
SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.
The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study
Authors: Caramello Valeria , Macciotta Alessandra , Bar Fabrizio , Mussa Alessandro , De Leo Anna Maria , De Salve Alessandro Vincenzo , Nota Fabio , Sacerdote Carlotta , Ricceri Fulvio , Boccuzzi Adriana 
Published: January 2022

Abstract
Background
Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature.
Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR).

Methods
We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients’ charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression.

Results
We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19.

Conclusions
In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result.
The relationship between telework from home and employee health: a systematic review
Authors: Lunde Lars-Kristian , Fløvik Lise , Christensen Jan Olav , Johannessen Håkon A. , Finne Live Bakke , Jørgensen Ingrid Løken , Mohr Benedicte , Vleeshouwers Jolien 
Published: January 2022

Abstract
Background
Globalization and technological progress have made telework arrangements such as telework from home (TWFH) well-established in modern economies. TWFH was rapidly and widely implemented to reduce virus spread during the Coronavirus disease (COVID-19) pandemic, and will probably be widespread also post-pandemic. How such work arrangements affect employee health is largely unknown. Main objective of this review was to assess the evidence on the relationship between TWFH and employee health.

Methods
We conducted electronic searches in MEDLINE, Embase, Amed, PsycINFO, PubMed, and Scopus for peer-reviewed, original research with quantitative design published from January 2010 to February 2021. Our aim was to assess the evidence for associations between TWFH and health-related outcomes in employed office workers. Risk of bias in each study was evaluated by the Newcastle-Ottawa Scale and the collected body of evidence was evaluated using the the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results
We included 14 relevant studies (22,919 participants) reporting on 28 outcomes, which were sorted into six outcome categories (general health, pain, well-being, stress, exhaustion & burnout, and satisfaction with overall life & leisure). Few studies, with many having suboptimal designs and/or other methodological issues, investigating a limited number of outcomes, resulted in the body of evidence for the detected outcome categories being GRADED either as low or very low.

Conclusions
The consisting evidence on the relationship between TWFH and employee health is scarce. The non-existence of studies on many relevant and important health outcomes indicates a vast knowledge gap that is crucial to fill when determining how to implement TWFH in the future working life.

Systematic review registration number
PROSPERO registration ID # CRD42021233796.
The many faces of diabetes. Is there a need for re-classification? A narrative review
Authors: Sakran Nasser , Graham Yitka , Pintar Tadeja , Yang Wah , Kassir Radwan , Willigendael Edith M. , Singhal Rishi , Kooreman Zoë E. , Ramnarain Dharmanand , Mahawar Kamal , Parmar Chetan , Madhok Brijesh , Pouwels Sjaak 
Published: January 2022

AbstractThe alarming rise in the worldwide prevalence of obesity and associated type 2 diabetes mellitus (T2DM) have reached epidemic portions. Diabetes in its many forms and T2DM have different physiological backgrounds and are difficult to classify. Bariatric surgery (BS) is considered the most effective treatment for obesity in terms of weight loss and comorbidity resolution, improves diabetes, and has been proven superior to medical management for the treatment of diabetes. The term metabolic surgery (MS) describes bariatric surgical procedures used primarily to treat T2DM and related metabolic conditions. MS is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Originally, BS was used as an alternative weight-loss therapy for patients with severe obesity, but clinical data revealed its metabolic benefits in patients with T2DM. MS is more effective than lifestyle or medical management in achieving glycaemic control, sustained weight loss, and reducing diabetes comorbidities. New guidelines for T2DM expand the use of MS to patients with a lower body mass index.Evidence has shown that endocrine changes resulting from BS translate into metabolic benefits that improve the comorbid conditions associated with obesity, such as hypertension, dyslipidemia, and T2DM. Other changes include bacterial flora rearrangement, bile acids secretion, and adipose tissue effect.This review aims to examine the physiological mechanisms in diabetes, risks for complications, the effects of bariatric and metabolic surgery and will shed light on whether diabetes should be reclassified.
Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells
Authors: Romero Juan José , De Rossi María Cecilia , Oses Camila , Echegaray Camila Vázquez , Verneri Paula , Francia Marcos , Guberman Alejandra , Levi Valeria 
Published: January 2022

Abstract
Background
The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive.

Results
We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role.

Conclusions
Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.
Effects of carrier solutions on the viability and efficacy of canine adipose-derived mesenchymal stem cells
Authors: Sultana Tania , Dayem Ahmed Abdal , Lee Soo Bin , Cho Ssang-Goo , Lee Jeong Ik 
Published: January 2022

Abstract
Background
Mesenchymal stem cells (MSCs) have favorable characteristics that render them a potent therapeutic tool. We tested the characteristics of MSCs after temporal storage in various carrier solutions, such as 0.9% saline (saline), 5% dextrose solution (DS), heparin in saline, and Hartmann’s solution, all of which are approved by the U.S. Food and Drug Administration (FDA). Phosphate-buffered saline, which does not have FDA approval, was also used as a carrier solution. We aimed to examine the effects of these solutions on the viability and characteristics of MSCs to evaluate their suitability and efficacy for the storage of canine adipose-derived MSCs (cADMSCs).

Results
We stored the cADMSCs in the test carrier solutions in a time-dependent manner (1, 6, and 12 h) at 4 °C, and analyzed cell confluency, viability, proliferation, self-renewability, and chondrogenic differentiation. Cell confluency was significantly higher in 5% DS and lower in phosphate-buffered saline at 12 h compared to other solutions. cADMSCs stored in saline for 12 h showed the highest viability rate. However, at 12 h, the proliferation rate of cADMSCs was significantly higher after storage in 5% DS and significantly lower after storage in saline, compared to the other solutions. cADMSCs stored in heparin in saline showed superior chondrogenic capacities at 12 h compared to other carrier solutions. The expression levels of the stemness markers, Nanog and Sox2, as well as those of the MSC surface markers, CD90 and CD105, were also affected over time.

Conclusion
Our results suggest that MSCs should be stored in saline, 5% DS, heparin in saline, or Hartmann’s solution at 4 °C, all of which have FDA approval (preferable storage conditions: less than 6 h and no longer than 12 h), rather than storing them in phosphate-buffered saline to ensure high viability and efficacy.
Horses’ rejection behaviour towards the presence of Senecio jacobaea L. in hay
Authors: Sroka Louisa , Müller Clara , Hass Marie-Lena , These Anja , Aboling Sabine , Vervuert Ingrid 
Published: January 2022

Abstract
Background
Senecio jacobaea contains pyrrolizidine alkaloids that can induce severe hepatic intoxication in horses, either acute when ingested in high amounts or chronic when consumed over a long period. The aim of this study was to determine horses’ rejection behaviour towards the presence of Senecio jacobaea in hay when fed ad libitum. We hypothesized that adult horses can sort Senecio jacobaea out of the contaminated hay when hay is fed ad libitum. Six warmblood geldings with a mean (±SD) age of 15 ± 2 years were included. In a randomized study, Senecio jacobaea contaminated hay (5% or 10% contamination level) was provided at several timepoints over the day for 1 hour to six. Hay was provided ad libitum for the rest of the day. The horses’ rejection behaviour towards Senecio jacobaea was observed. If a horse ingested two Senecio jacobaea plants twice at different timepoints, then the horse was excluded from the experiment.

Results
Two out of six horses had to be excluded from the study after three out of 12 observation periods due to repeated Senecio jacobaea intake. Two other horses had to be excluded after nine and 11 out of 12 observation periods. Only two horses were able to sort out the various amounts (5 and 10% contamination level) of Senecio jacobaea during the whole experiment.

Conclusions
Horses’ intake of Senecio jacobaea cannot be avoided despite being fed with hay ad libitum. Due to the risk of chronic intoxication by pyrrolizidine alkaloids intake, feeding Senecio jacobaea contaminated hay must be avoided, and pastures with Senecio jacobaea growth are considered inappropriate for feed production.
Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene
Authors: Marei Hany E. , Althani Asmaa , Afifi Nahla , Hasan Anwarul , Caceci Thomas , Felsani Armando , Tringali Giuseppe , Cifola Ingrid , Pozzoli Giacomo , Cenciarelli Carlo 
Published: January 2022

Abstract
Background
Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes.

Methods
In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development.

Results
By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency.

Conclusions
We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.
Triglyceride/low-density-lipoprotein cholesterol ratio is the most valuable predictor for increased small, dense LDL in type 2 diabetes patients
Authors: Ouchi Gen , Komiya Ichiro , Taira Shinichiro , Wakugami Tamio , Ohya Yusuke 
Published: January 2022

Abstract
Background
Small, dense low-density lipoprotein (sd-LDL) increases in type 2 diabetes patients and causes arteriosclerosis. Non–high-density-lipoprotein cholesterol (non–HDL-C) is thought to be useful for predicting arteriosclerosis and sd-LDL elevation; however, there are no data about whether the triglyceride /low-density-lipoprotein cholesterol (TG/LDL-C) ratio is a valuable predictor for sd-LDL.

Methods
A total of 110 type 2 diabetes patients with hypertriglyceridemia were analyzed. No patients were treated with fibrates, but 47 patients were treated with statins. LDL-C was measured by the direct method. LDL-migration index (LDL-MI) using electrophoresis (polyacrylamide gel, PAG) was calculated, and a value ≥0.400 was determined to indicate an increase in sd-LDL. Simple regression analyses were carried out between LDL-MI and lipid markers. Receiver operating characteristic curves of lipid markers for predicting high LDL-MI were applied to determine the area under the curve (AUC), sensitivity, specificity, and cut-off point.

Results
LDL-MI correlated negatively with LDL-C (P = 0.0027) and PAG LDL fraction (P < 0.0001) and correlated positively with TGs, non–HDL-C, TG/LDL-C ratio, TG/HDL-C ratio, and non–HDL-C/HDL-C ratio among all study patients. Similar results were obtained for patients analyzed according to statin treatment. The AUCs (95% confidence interval) were 0.945 (0.884-1.000) for TG/LDL-C ratio and 0.614 (0.463-0.765) for non–HDL-C in patients without statins (P = 0.0002). The AUCs were 0.697 (0.507-0.887) for TG/LDL-C and 0.682 (0.500-0.863) for non–HDL-C in patients treated with statins. The optimal cut-off point for TG/LDL-C ratio for increased LDL-MI was 1.1 (molar ratio) regardless of statin treatment. The sensitivity and specificity of the TG/LDL-C ratio (90.0 and 93.9%, respectively) were higher than those of non–HDL-C (56.7 and 78.8%, respectively) in patients without statins.

Conclusions
The TG/LDL-C ratio is a reliable surrogate lipid marker of sd-LDL and superior to non–HDL-C in type 2 diabetes patients not treated with statins.