bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low levels of BRCA1 protein expression predict a worse prognosis in stage I–II colon cancer
Authors: Du Changzheng , Peng Yifan , He Yiping , Chen Guoan , Chen Hao 
Published: February 2021

Background: BRCA1 and BRCA2 have been well studied for their roles in tumorigeneis, plus cancer diagnosis and treatment, but their prognostic value in colon cancer, especially for early-stage cancer, has not been fully illuminated. This study examined the expression levels of BRCA1 and BRCA2 proteins in sporadic colon cancer cases and investigated their value in prognosis. Methods: The expression levels of BRCA1 and BRCA2 in 275 colon cancer patients who underwent radical surgeries were assayed by immunohistochemical staining in dissected tumor samples. Also, its correlation with clinicopathological characteristics, disease-free survival, and overall survival was investigated. Results: Tumors with low expression levels of BRCA1, BRCA2, and both were 19.6%, 17.8%, and 6.5%, respectively. The levels of BRCA1/2 expression were not associated with clinicopathological parameters (gender, age, histological differentiation, and tumor node metastasis stage). Patients with low-levels of BRCA1 protein in their tumors demonstrated a lower chance of 5-year disease-free survival (55.6% vs. 69.7%, P=0.046), which was more obvious in the patients with stage I–II tumors without chemotherapy (52.6% vs. 82.6%, P=0.006). Neither BRCA1 nor BRCA2 affected overall survival in this cohort. Multivariate analysis revealed that pathologic stage and the level of BRCA1 protein were independent factors of long-term disease-free survival. Conclusion: This study highlights BRCA1 as an independent prognosticator of early-stage colon cancer.
Rapid component of excess post-exercise oxygen consumption of children of different weight status after playing active video games
Authors: Sousa Caio Victor , Hwang Jungyun , Simoes Herbert Gustavo , Sun Kyung Jin , Lu Amy Shirong 
Published: February 2021

Abstract
Background
Excess post-exercise oxygen consumption (EPOC) of children could indicate the potential of an exercise therapy to treat or prevent obesity. However, EPOC as a result of playing active video games (AVG) has been poorly investigated. Therefore, we aimed to investigate the rapid component of EPOC of children with healthy weight and overweight/obesity (according to their BMI percentile) after playing AVGs that feature predominately upper body (UB) and whole-body (WB) movement.

Methods
Twenty-one children with healthy weight (BMI percentile < 85%) and with overweight/obesity (BMI percentile ≥ 85%) randomly underwent two 10-min AVG sessions (UB and WB). The heart rate (HR), minute ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (VCO2) were recorded during exercise and post-exercise recovery period. For the rapid component of EPOC in each AVG session, measurements were recorded every 15 s for 5-min of post-exercise recovery. The rate of perceived exertion (RPE) was also measured immediately before and after each AVG play.

Results
Children with overweight/obesity had a higher average of absolute VE, VO2, and VCO2 than their healthy-weight counterparts (BMI percentile < 85%; n = 21) during post-exercise recovery. RPE, HR, and HR% were not different between the game sessions and weight groups. Children with overweight/obesity showed a higher absolute VO2 during EPOC than healthy-weight children in both game sessions, but relative VO2 was higher in healthy-weight children during EPOC. No differences were observed for EPOC between UB and WB sessions.

Conclusions
Children with overweight/obesity had a greater EPOC than healthy-weight children after AVG sessions in terms of absolute oxygen values, whereas healthy-weight children have higher EPOC considering relative VO2 when controlling for body mass. UB and WB AVGs induced a similar EPOC among children with healthy weight and overweight/obesity. As UB and WB AVGs induce the rapid component of EPOC in children regardless their weight status, AVGs could be used as an exercise method to treat and prevent child obesity.
Genetic variants and physical activity interact to affect bone density in Hispanic children
Authors: Hou Ruixue , Cole Shelley A. , Graff Mariaelisa , Wang Yujie , Haack Karin , Laston Sandra , Mehta Nitesh R. , Shypailo Roman J. , Gourlay Margaret L. , Comuzzie Anthony G. , North Kari E. , Butte Nancy F. , Voruganti Venkata Saroja 
Published: February 2021

Abstract
Background
Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods
Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD.

Results
We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (β = − 0.040 ± 0.009, p = 1.1 × 10− 5) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively).

Discussion
The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed.

Conclusions
Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.
Muscle activity and acute stress in fibromyalgia
Authors: Zetterman Teemu , Markkula Ritva , Partanen Juhani V. , Miettinen Teemu , Estlander Ann-Mari , Kalso Eija 
Published: February 2021

AbstractBackgroundFibromyalgia (FM) patients are likely to differ from healthy controls in muscle activity and in reactivity to experimental stress.MethodsWe compared psychophysiological reactivity to cognitive stress between 51 female FM patients aged 18 to 65 years and 31 age- and sex-matched healthy controls. They underwent a 20-minute protocol consisting of three phases of relaxation and two phases of cognitive stress. We recorded surface electromyography normalized to maximum voluntary muscle contraction (%EMG), the percentage of time with no muscle activity (EMG rest time), and subjective pain and stress intensities. We compared group reactivity using linear modelling and adjusted for psychological and life-style factors.ResultsThe FM patients had a significantly higher mean %EMG (2.2 % vs. 1.0 %,p < 0.001), pain intensity (3.6 vs. 0.2,p < 0.001), and perceived stress (3.5 vs. 1.4,p < 0.001) and lower mean EMG rest time (26.7 % vs. 47.2 %,p < 0.001). In the FM patients, compared with controls, the pain intensity increased more during the second stress phase (0.71,p = 0.028), and the %EMG decreased more during the final relaxation phase (-0.29,p = 0.036). Within the FM patients, higher BMI predicted higher %EMG but lower stress. Leisure time physical activity predicted lower %EMG and stress and higher EMG rest time. Higher perceived stress predicted lower EMG rest time, and higher trait anxiety predicted higher pain and stress overall.ConclusionsOur results suggest that repeated cognitive stress increases pain intensity in FM patients. FM patients also had higher resting muscle activity, but their muscle activity did not increase with pain. Management of stress and anxiety might help control FM flare-ups.Trial registrationRetrospectively registered on ClinicalTrials.gov (NCT03300635).
Pan-dent-emic: a dentist’s dilemma in the COVID-19 era
Authors: Manaktala Nidhi , Pralhad Swati , M Roma 
Published: February 2021

AbstractThe aftermath of the COVID-19 pandemic has been unfathomable. It has affected every sector within health care industry with dentistry being one of the worst hits. Not only has it impacted the dental practice, the field of dental education has been affected as well. There has been loss in terms of delayed to no treatments, finances, psychology and most importantly breaks in ongoing education and research practices. The present article attempts to explain the dilemma of the current situation from a dentist’s perspective. Since, the effects of the contagion are seen across each level of dentistry, the current situation can truly be termed as a “Pan-dent-emic”.
Development and evaluation of an interactive web-based decision-making programme on relapse management for people with multiple sclerosis (POWER@MS2)—study protocol for a randomised controlled trial
Authors: Rahn Anne Christin , Wenzel Lisa , Icks Andrea , Stahmann Alexander , Scheiderbauer Jutta , Grentzenberg Kristina , Vomhof Markus , Montalbo Joseph , Friede Tim , Heesen Christoph , Köpke Sascha 
Published: February 2021

AbstractIntroductionMultiple sclerosis is a chronic inflammatory, degenerative disease of the central nervous system manifesting at first with relapses in about 85% of cases. In Germany, intravenous therapy with high-dose corticosteroids is the treatment standard of acute relapses. The treatment leads to a faster reduction of symptoms in about 25 of 100 treated patients but has no proven long-term benefits over placebo treatment. Intravenous treatment is not superior to oral treatment. Therefore, informed decisions on relapse management are required. An earlier randomised controlled trial showed that evidence-based patient information and education on relapse management leads to more informed decisions and more relapses not treated or treated with oral corticosteroids. This study aims to evaluate whether a web-based relapse management programme will positively change relapse management and strengthen autonomy in people with multiple sclerosis.MethodsThe pragmatic double-blind randomised controlled trial is accompanied by a mixed-methods process evaluation and a health economic evaluation and follows the UK Medical Research Council guidance on developing and evaluating complex interventions. A total of 188 people with possible or relapsing-remitting multiple sclerosis with ≥ 1 relapse within the last year and/or ≥ 2 relapses within the last 2 years will be recruited and randomised using blocks. The intervention group receives a web- and dialogue-based decision aid on relapse management, a nurse-led webinar and access to a monitored chat forum. The control group receives standard information, which will be made available via the same online platform as the intervention. The primary endpoint is the proportion of relapses not treated or treated with oral corticosteroids. Key secondary endpoints are the annualised relapse rate, decision-making, empowerment, quality of life and cost-effectiveness. Facilitators and barriers will be assessed by mixed-methods process evaluation measures. The study ends when 81 relapses have been documented or after 24 months of observation per individual patient. Analyses will follow the intention-to-treat principle.DiscussionWe hypothesise that the intervention will enhance patient empowerment and have a positive impact on patients’ relapse management.Trial registrationClinicalTrials.govNCT04233970. Registered on 18 January 2020
Reproductive fluids, used for the in vitro production of pig embryos, result in healthy offspring and avoid aberrant placental expression of PEG3 and LUM
Authors: París-Oller E. , Navarro-Serna S. , Soriano-Úbeda C. , Lopes J. S. , Matás C. , Ruiz S. , Latorre R. , López-Albors O. , Romar R. , Cánovas S. , Coy P. 
Published: February 2021

Abstract
Background
In vitro embryo production (IVP) and embryo transfer (ET) are two very common assisted reproductive technologies (ART) in human and cattle. However, in pig, the combination of either procedures, or even their use separately, is still considered suboptimal due to the low efficiency of IVP plus the difficulty of performing ET in the long and contorted uterus of the sow. In addition, the potential impact of these two ART on the health of the offspring is unknown. We investigated here if the use of a modified IVP system, with natural reproductive fluids (RF) as supplements to the culture media, combined with a minimally invasive surgery to perform ET, affects the output of the own IVP system as well as the reproductive performance of the mother and placental molecular traits.

Results
The blastocyst rates obtained by both in vitro systems, conventional (C-IVP) and modified (RF-IVP), were similar. Pregnancy and farrowing rates were also similar. However, when compared to in vivo control (artificial insemination, AI), litter sizes of both IVP groups were lower, while placental efficiency was higher in AI than in RF-IVP. Gene expression studies revealed aberrant expression levels for PEG3 and LUM in placental tissue for C-IVP group when compared to AI, but not for RF-IVP group.

Conclusions
The use of reproductive fluids as additives for the culture media in pig IVP does not improve reproductive performance of recipient mothers but could mitigate the impact of artificial procedures in the offspring.
Modelling an unconventional closed-loop deep borehole heat exchanger (DBHE): sensitivity analysis on the Newberry volcanic setting
Authors: Doran Hannah R. , Renaud Theo , Falcone Gioia , Pan Lehua , Verdin Patrick G. 
Published: February 2021

AbstractAlternative (unconventional) deep geothermal designs are needed to provide a secure and efficient geothermal energy supply. An in-depth sensitivity analysis was investigated considering a deep borehole closed-loop heat exchanger (DBHE) to overcome the current limitations of deep EGS. A T2Well/EOS1 model previously calibrated on an experimental DBHE in Hawaii was adapted to the current NWG 55-29 well at the Newberry volcano site in Central Oregon. A sensitivity analysis was carried out, including parameters such as the working fluid mass flow rate, the casing and cement thermal properties, and the wellbore radii dimensions. The results conclude the highest energy flow rate to be 1.5 MW, after an annulus radii increase and an imposed mass flow rate of 5 kg/s. At 3 kg/s, the DBHE yielded an energy flow rate a factor of 3.5 lower than the NWG 55-29 conventional design. Despite this loss, the sensitivity analysis allows an assessment of the key thermodynamics within the wellbore and provides a valuable insight into how heat is lost/gained throughout the system. This analysis was performed under the assumption of subcritical conditions, and could aid the development of unconventional designs within future EGS work like the Newberry Deep Drilling Project (NDDP). Requirements for further software development are briefly discussed, which would facilitate the modelling of unconventional geothermal wells in supercritical systems to support EGS projects that could extend to deeper depths.
Development and validation of the method for the detection of glimepiride via derivatization employing N-methyl-N-(trimethylsilyl) trifluoroacetamide using gas chromatography-mass spectrometry
Authors: Verma Priyanka , Bajaj Atul , Tripathi R. M. , Shukla Sudhir K. , Nagpal Suman 
Published: February 2021

Abstract
Background
Recent advances in the diversified anti-diabetic drugs have appeared in the startling increase in the count of poisoning cases. The epidemics of diabetes mellitus are increasing; hence, the no. of anti-diabetic drug users raised by 42.9%. The use of glimepiride raised to 24%. As the toxicity and drug cases are also escalating with increasing epidemics of diabetes mellitus, a novel gas chromatography-mass spectrometry (GC-MS) method for detecting glimepiride in biological matrices is developed.

Results
Liquid-liquid extraction method was employed by using 1-butanol: hexane (50:50, v/v) under an alkaline medium, and then back extraction was done via acetic acid. Distinct derivatization techniques were employed for the sample preparation for GC-MS analysis, i.e., silylation and acylation. Derivatization approaches were optimized under different parameters, i.e., reaction temperature and reaction time. N-Methyl-N-(trimethylsilyl) trifluoroacetamide [MSTFA] was found to be the best sound derivatization reagent for the GC-MS analysis of glimepiride. Total ion current (TIC) mode was selected for the monitoring of ions of trimethylsilyl (TMS) derivative of glimepiride with an m/z ratio of 256. Distinct parameters like specificity, carryover, stability, precision, and accuracy were evaluated for validating the identification method. The GC-MS method is found to be linear and illustrated within the range 500 to 2500 ng/ml with the value of R2 (coefficient of determination) at 0.9924. The stability of the extracted and derivatized glimepiride was accessed with regard to processed/extracted sample conditions and autosampler conditions, respectively. Accuracy at each concentration level was within the + 15% of the nominal concentration. Precision (%) for the interday and intraday analysis was found to be in the respectable spectrum.

Conclusion
Henceforth, the proposed GC-MS method can be employed for the determination of glimepiride in biological matrices.
Biomedical application of photo-crosslinked gelatin hydrogels
Authors: Xiang Lei , Cui Wenguo 
Published: February 2021

AbstractDuring the past decades, photo-crosslinked gelatin hydrogel (methacrylated gelatin, GelMA) has gained a lot of attention due to its remarkable application in the biomedical field. It has been widely used in cell transplantation, cell culture and drug delivery, based on its crosslinking to form hydrogels with tunable mechanical properties and excellent bio-compatibility when exposed to light irradiation to mimic the micro-environment of native extracellular matrix (ECM). Because of its unique biofunctionality and mechanical tenability, it has also been widely applied in the repair and regeneration of bone, heart, cornea, epidermal tissue, cartilage, vascular, peripheral nerve, oral mucosa, and skeletal muscle et al. The purpose of this review is to summarize the recent application of GelMA in drug delivery and tissue engineering field. Moreover, this review article will briefly introduce both the development of GelMA and the characterization of GelMA. Finally, we discuss the challenges and future development prospects of GelMA as a tissue engineering material and drug or gene delivery carrier, hoping to contribute to accelerating the development of GelMA in the biomedical field.Graphical abstract
Identification of the most potent acetylcholinesterase inhibitors from plants for possible treatment of Alzheimer’s disease: a computational approach
Authors: Sarkar Bishajit , Alam Sayka , Rajib Tiluttoma Khan , Islam Syed Sajidul , Araf Yusha , Ullah Md. Asad 
Published: February 2021

Abstract
Background
Being one of the rapidly growing dementia type diseases in the world, Alzheimer’s disease (AD) has gained much attention from researchers in the recent decades. Many hypotheses have been developed that describe different reasons for the development of AD. Among them, the cholinergic hypothesis depicts that the degradation of an important neurotransmitter, acetylcholine by the enzyme acetylcholinesterase (AChE), is responsible for the development of AD. Although, many anti-AChE drugs are already available in the market, their performance sometimes yields unexpected results. For this reason, research works are going on to find out potential anti-AChE agents both from natural and synthetic sources. In this study, 50 potential anti-AChE phytochemicals were analyzed using numerous tools of bioinformatics and in silico biology to find out the best possible anti-AChE agents among the selected 50 ligands through molecular docking, determination of the druglikeness properties, conducting the ADMET test, PASS and P450 site of metabolism prediction, and DFT calculations.

Result
The predictions of this study suggested that among the selected 50 ligands, bellidifolin, naringenin, apigenin, and coptisine were the 4 best compounds with quite similar and sound performance in most of the experiments.

Conclusion
In this study, bellidifolin, naringenin, apigenin, and coptisine were found to be the most effective agents for treating the AD targeting AChE. However, more in vivo and in vitro analyses are required to finally confirm the outcomes of this research.
Association of working hours, job position, and BMI with work-related musculoskeletal disorders among the physiotherapists of Gujarat—an observational study
Authors: Ramanandi Vivek H. , Desai Anjan R. 
Published: February 2021

Abstract
Background
Physiotherapists are prone to develop work-related musculoskeletal disorders (WMSDs). Region wise distribution and frequency of work disturbance have been studied in physiotherapists but exploration of the probable association of working hours, job position, and body mass index (BMI) with WMSDs is not adequately done in the Gujarat, India. Hence, the present study was undertaken to investigate these aspects among the physiotherapists of Gujarat.

Results
An online cross-sectional survey including 322 physiotherapists was conducted and the data was collected after gaining informed electronic consent. Present study showed no significant co-relation between job position (0.602), weekly working hours (0.930), and BMI (0.589) with WMSDs prevalence. The 1-year work disturbance and 1-week musculoskeletal difficulties were found to be due to low back-related complaints (35.09%, 33.85%).

Conclusion
It is inferred that high prevalence of WMSDs in physiotherapists may be due to one of various factors including job position, working hours, and BMI but they are not significantly correlated with WMSDs.
Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil
Authors: Levine Stephen Z. , Goldberg Yair , Yoshida Kazufumi , Samara Myrto , Cipriani Andrea , Iwatsubo Takeshi , Leucht Stefan , Furawaka Toshiaki A. 
Published: February 2021

AbstractBackgroundThe extent and profiles of heterogeneity in cognitive functioning among participants in clinical trials of antidementia medication are unknown. We aimed to quantify and identify profiles of heterogeneity of cognition in Alzheimer’s disease.MethodsIndividual-level participant data were analyzed from five pivotal clinical trials of donepezil for Alzheimer’s disease (N = 2,919). Based on Alzheimer’s Disease Assessment Scale–Cognitive Subscale total scores from baseline up to week 12, a latent class model was used to identify heterogeneous groups. A logistic regression model was used to examine factors associated with group membership. Sensitivity analysis was conducted, restricted to the donepezil, and then the placebo arm.ResultsThe latent class model identified three classes labeled as low scorers (i.e., least cognitive impairment;N = 1,666, 76.04%), improvers (N = 27, 1.23%), and high scorers (N = 498, 22.73%). Logistic modeling showed that donepezil compared to placebo was significantly (p < 0.05) positively associated with membership in the improvers class (OR = 6.88, 95% CI = 2.03, 42.95), and negatively with high scorers (OR = 0.79, 95% CI = 0.64, 0.98). Sensitivity analysis restricted to the placebo, then donepezil arms replicated similar heterogeneity patterns.ConclusionsOur results inform clinicians regarding the extent of heterogeneity in cognitive functioning during treatment and contribute to trial design considerations.