bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of CRISPR/Cas9-based mutant enrichment technique to improve the clinical sensitivity of plasma EGFR testing in patients with non-small cell lung cancer
Authors: Kim Boyeon , Kim Yoonjung , Shin Saeam , Lee Seung-Tae , Cho Jae Yong , Lee Kyung-A 
Published: September 2021

Abstract
Background
Mutation detection in cell-free DNA (cfDNA) has increased and is becoming important in the field of precision medicine. Highly fragmented, low-quantity circulating tumor DNA is an obstacle for detecting mutations. Therefore, more sensitive mutation detection techniques are required. Here, we report a new mutant enrichment technology, the CRISPR system combined with post-polymerase chain reaction (PCR) cfDNA (CRISPR-CPPC) to detect the T790M mutation using droplet digital PCR (ddPCR) from cfDNA with extremely low mutant allele copies.
Methods
The CRISPR-CPPC process comprises the following three steps: (1) cfDNA PCR, (2) assembly of post-PCR cfDNA and CRISPR/CRISPR associated protein 9 complex, and (3) enrichment of the target DNA template. After CRISPR-CPPC, the target DNA can be detected using a variety of downstream applications. We optimized and validated CRISPR-CPPC using reference cfDNA standards and cfDNA from patients with non-small cell lung cancer (NSCLC) who underwent tyrosine kinase inhibitor (TKI) therapy. We then compared the detection sensitivity of CRISPR-CPPC with the results of real-time PCR (qPCR) and those of ddPCR without CRISPR-CPPC.
Results
CRISPR-CPPC aided detection of T790M with 93.9% sensitivity and 100% specificity in patients with progressive disease. Using CRISPR-CPPC, T790M mutant copies were sensitively detected by ddPCR, achieving an approximately 13-fold increase in the detected allele frequency.
Conclusions
When tested in patients with progressive disease, the performance of CRISPR CPPC was exceptionally higher than that of other currently available methods. CRISPR-CPPC can greatly contribute to diagnosis and the selection of appropriate treatment regimens by facilitating the sensitive detection of mutations in cfDNA.
Association of Decreased Muscle Mass with Reduced Bone Mineral Density in Patients with Graves’ disease
Authors: Zhang Yongze , Huang Lingning , Ke Yuzhen , Lin Yuxi , Shen Ximei , Zhao Fengying , Li Yimei , Yan Sunjie 
Published: September 2021

Abstract
Background
The bone mineral density (BMD) did not increase significantly after the normalization of serum thyroid hormone levels. Studies on the effect of muscle mass on BMD in patients with Graves’ disease are scarce. This study aimed to determine the association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease.
Methods
A total of 758 patients with Graves’ at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 patients were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls participants were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and BMD were calculated from the measurements made at a gap of 2 years.
Results
Compared with healthy controls participants, the BMD was still significantly lower after normalizing serum thyroid hormone levels (1.131 ± 0.268 vs. 1.07 ± 0.133, p < 0.05). ASMI was positively related to BMD in patients with Graves’ disease(lumbar BMD, r = 0.210; femoral neck BMD, r = 0.259;hip BMD, r = 0.235;P < 0.001) and this relationship still existed after successful anti-thyroid therapy(lumbar BMD, r = 0.169; femoral neck BMD, r = 0.281;hip BMD, r = 0.394;P < 0.001). Low muscle mass was associated with low BMD (OR, 1.426; 95% CI, 1.019–1.994). Moreover, improving the muscle mass led to changes in the bone mass of the femoral neck (OR, 0.420; 95% CI, 0.194–0.911) and hip (OR, 0.217; 95% CI, 0.092–0.511) during the follow-up period. However, this phenomenon was not observed in lumbar, and bone turnover markers.
Conclusions
The recovery of bone mass might be related to the recovery of muscle mass. Improving muscle mass might bring about changes in the bone mass of the femoral neck and hip. A site-related discrepancy was also observed. Patients with Graves’ disease should be helped in recovering muscle mass while administering anti-thyroid therapy.
Prediction of sperm progression in three dimensions using rapid optical imaging and dynamic mechanical modeling
Authors: Nassir Mayssam , Levi Mattan , Dardikman-Yoffe Gili , Mirsky Simcha K. , Shaked Natan T. 
Published: September 2021

Abstract
We present a multidisciplinary approach for predicting how sperm cells with various morphologies swim in three-dimensions (3D), over time scales of milliseconds to hours at spatial resolutions of less than half a micron. We created the sperm 3D geometry and built a numerical mechanical model using the experimentally acquired dynamic 3D refractive index profiles of sperm cells swimming freely in vitro as imaged by high-resolution optical diffraction tomography. By controlling parameters in the model, such as the size and shape of the sperm head and tail, we can then predict how different sperm cells, normal or abnormal, would swim in 3D, in the short or long term. We quantified various 3D structural factor effects on the sperm long-term motility. We found that some abnormal sperm cells swim faster than normal sperm cells, in contrast to the commonly-used sperm selection assumption during IVF, according to which sperm cells should mainly be chosen based on their progressive motion. We established a new tool for sperm analysis and male-infertility diagnosis, as well as new sperm selection criteria for fertility treatments.
Longitudinal changes in maternal circulating microRNAs as potential biomarkers of specific events during healthy pregnancy
Authors: Chavira-Suárez Erika , Hernández-Olvera Alma Lilia , Flores-Torres Mariana , Celaya-Cruz Karen Rubí , Gitler Sofía , Cerda-Ángeles Juan Carlos De la , Espinosa-Maldonado Nidia Carolina , Flores-Jasso Carlos Fabián , Gutiérrez Humberto , Vadillo-Ortega Felipe 
Published: September 2021

Abstract
BackgroundNovel high-resolution tools for pregnancy monitoring, including early detection of prenatal disorders, are needed. Changes in circulating microRNAs (c-miRNAs) during pregnancy could potentially inform about the functional status of the mother, the placenta and/or the fetus. However, whether c-miRNA profiles actually reflect distinct pregnancy-specific events at all stages remains unclear.MethodsLongitudinal large-scale RNAseq c-miRNA profiles at early, middle and late pregnancy, and after birth derived from eight women with healthy term pregnancies (n = 32 plasma samples) were compared against corresponding circulating profiles derived from age-matched non-pregnant women (n = 10). Data of fetal sex and growth indicators obtained during pregnancy evolution of the same women, were used to identify specific c-miRNA correlates in circulation.Results1449 c-miRNAs were detected in circulation in both pregnant and non-pregnant women with only 48 c-miRNAs differentially expressed relative to non-pregnant controls in at least one of the four studied stages (FDR < 0.05). Surprisingly, c-miRNA subpopulations with reported prominent expression in various pregnancy-associated compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found collectively under-expressed in maternal circulation throughout pregnancy (p < 0.05). Furthermore, we found a bias in global miRNAs expression in direct association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth (R = 0.7, p < 0.01).ConclusionOur results demonstrate the existence of temporal changes in c-miRNAs populations associated to distinct aspects of pregnancy, including correlates of placental function and lactation, as well as fetal gender and growth, revealing a wider potential of c-miRNAs as biomarkers of specific aspects of maternal health and fetal growth.
Training Calibration-based Counterfactual Explainers for Deep Learning Models in Medical Image Analysis
Authors: Thiagarajan Jayaraman J. , Thopalli Kowshik , Rajan Deepta , Turaga Pavan 
Published: September 2021

Abstract
Artificial intelligence methods such as deep neural networks promise unprecedented capabilities in healthcare, from diagnosing diseases to prescribing treatments. While this can eventually produce a valuable suite of tools for automating clinical workflows, a critical step forward is to ensure that the predictive models are reliable and to enable a rigorous introspection of their behavior. This has led to the design of explainable AI techniques that are aimed at uncovering the relationships between discernible data signatures and decisions from machine-learned models, and characterizing strengths/weaknesses of models. In this context, the so-called counterfactual explanations that synthesize small, interpretable changes to a given query sample while producing desired changes in model predictions to support user-specified hypotheses (e.g., progressive change in disease severity) have become popular. When a model’s predictions are not well-calibrated (i.e., the prediction confidences are not indicative of the likelihood of the predictions being correct), the inverse problem of synthesizing counterfactuals can produce explanations with irrelevant feature manipulations. Hence, in this paper, we propose to leverage prediction uncertainties from the learned models to better guide this optimization. To this end, we present TraCE (Training Calibration-based Explainers), a counterfactual generation approach for deep models in medical image analysis, which utilizes pre-trained generative models and a novel uncertainty-based interval calibration strategy for synthesizing hypothesis-driven explanations. By leveraging uncertainty estimates in the optimization process, TraCE can consistently produce meaningful counterfactual evidences and elucidate complex decision boundaries learned by deep classifiers. Furthermore, we demonstrate the effectiveness of TraCE in revealing intricate relationships between different patient attributes and in detecting shortcuts, arising from unintended biases, in learned models. Given the widespread adoption of machine-learned solutions in radiology, our study focuses on deep models used for identifying anomalies in chest X-ray images. Using rigorous empirical studies, we demonstrate the superiority of TraCE explanations over several state-of-the-art baseline approaches, in terms of several widely adopted evaluation metrics in counterfactual reasoning. Our findings show that TraCE can be used to obtain a holistic understanding of deep models by enabling progressive exploration of decision boundaries, detecting shortcuts, and inferring relationships between patient attributes and disease severity.
Effect of Food Insecurity On The Cognitive Problems Among Elderly In India
Authors: Kumar Shubham , Bansal Anjali , Shri Neha , Nath Nayan Jyothi , Dosaya Divya 
Published: September 2021

Abstract
Background: Food Insecurity (FI) is a crucial social determinant of health, independent of other socioeconomic factors, as inadequate food resources create a threat to physical and mental health especially among older person. The present study explores the associations between FI and cognitive ability among the aged population in India. Methods: We have used the data from the first wave of longitudinal ageing study of India (LASI), with a sample of 31,464 older persons 60 years and above. To measure the cognitive functioning we have used two proxies, word recall and computational problem. Descriptive analysis and multivariable logistic regression was used to understand the prevalence of word recall and computational problem by food security and some selected sociodemographic parameters. All the results were reported at 95% confidence interval. Results: The study identified that 17% and 5% of the older population in India experiencing computational and word recall problem, respectively. It was found that respondents from food secure households were 14 percent less likely to have word recall problems [AOR:0.86, 95% CI:0.31-0.98], and 55 percent likely to have computational problems [AOR:0.45, 95% CI:0.29-0.70]. We also found poor cognitive functioning among those experiencing disability, severe ADL, and IADL. Further, factors such as age, education, marital status, working status, health related factors were the major contributors to the cognitive functioning in older adults. Conclusion: This study suggest that food insecurity is associated with a lower level of cognition among the elderly in India, which highlight the need of food policy and interventional strategies to address food insecurity, especially among the individuals belonging to lower wealth quintiles. Furthermore, increasing the coverage of food distribution may also help to decrease the burden of disease for the at most risk population. Also, there is a need for specific programs and policies that improve the availability of nutritious food among elderly.
The effect of a modified chevron osteotomy for hallux valgus patients: A five-year follow-up study
Authors: Zhang Shiyong , Wang Xue , Chen Tiannan , Wang Chengwei , Wang Jie 
Published: September 2021

Abstract
Purpose

This study aimed to detect the effect of a modified chevron osteotomy on hallux valgus (HV) deformity at five-year follow up.
Methods

Twenty patients with symptomatic HV who underwent modified chevron osteotomy between June 2014 and January 2016 were included in the present study. The follow-up duration was more than five years. Each patient was evaluated preoperatively, six weeks postoperatively and five years postoperatively using the visual analog scale (VAS) pain score, the American Orthopaedic Foot & Ankle Society (AOFAS) score and cosmetic and radiological outcomes.
Results

The AOFAS score improved from 54.40 (± 4.58) preoperatively to 94.30 (± 2.15) six weeks postoperatively (p < 0.001) and 96.95 (± 1.54) five years postoperatively (p < 0.001). The VAS scores decreased from 6.30 (± 1.17)preoperatively to 0.15 (± 0.37) five years postoperatively (p < 0.001). The mean intermetatarsal angle improved from 16.00° (± 2.20°) preoperatively to 4.15° (± 1.22°) six weeks postoperatively (p < 0.001) and 4.40° (± 1.39°) five years postoperatively (p < 0.001). The mean HV angle also improved, from 32.70° (± 5.34°) preoperatively to 4.80° (± 1.40°) six weeks postoperatively (p < 0.001) and 5.20° (± 1.32°) five years postoperatively (p < 0.001). The cosmetic results were either excellent or good in 19 patients (95%). There was no recurrence in this study during the five postoperative years.
Conclusion

A modified chevron osteotomy can achieve successful correction of moderate-to-severe HV, with excellent outcomes at five-year follow up.
Adverse effects of COVID-protective face-masks and wearing durations onto respiratory-haemodynamic physiology and exhaled breath constituents
Authors: Sukul Pritam , Bartels Julia , Fuchs Patricia , Trefz Phillip , Remy Rasmus , Rührmund Leo , Kamysek Svend , Schubert Jochen K , Miekisch Wolfram 
Published: September 2021

Abstract

While protecting against the coronavirus transmission, face-masks may have adverse effects on respiratory-haemodynamic parameters. We investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 healthy volunteers at rest. We continuously monitored exhaled breath profiles in the mask space in elderly (age: 60–80 years) and adults (age: 20–60 years) over a period of 30 min by high-resolution real-time mass-spectrometry (PTR-ToF-MS). Peripheral oxygen saturation, respiratory- and haemodynamic parameters were measured (non-invasively) continuously in parallel. Profound and consistent decrease in SpO2 and increase in pET-CO2 indicates ascending deoxygenation and inadequate ventilation in subjects. Cardiac output and MAP changed as secondary. Exhalation of blood-borne volatile metabolites mirrored behaviour of cardiac output, MAP, SpO2, respiratory rate and pET-CO2. FFP2 masks affected more pronouncedly than surgical masks. Elderly cohort was more vulnerable to those effects. Exhaled humidity increased and exhaled oxygen decreased significantly over time. Breath profiles of endogenous aldehydes, hemiterpene, organosulfur, short-chain fatty acids, alcohols and ketone indicated cross-talks between physio-metabolic effects such as hypoxia, oxidative stress, hypoventilation, compartmental vasoconstriction, altered systemic bacterial activity and energy homeostasis. Concentrations of exogenous VOCs such as aromatics, nitrile and monoterpene depicted compartmental storage and washout. Breathomics allows unique physio-metabolic insights into side effects of face-mask wearing. Mask induced deoxygenation, oxidative stress, CO2 rebreathing, vasoconstriction and blood pressure fluctuations in elderly were clinically concerning (as leading towards hypoxia and hypoventilation). Intelligible global-pandemic policies should reconsider the type and wearing durations of recommended face-masks, based upon age and/or cardio-pulmonary conditions.
Efficient Oil-Water Separation Coating With Robust Superhydrophobicity and High Transparency
Authors: Chen Baiyi , Zhang Rongrong , Fu Hexuan , Xu Jiadai , Jing Yuan , Xu Guohe , Hou Xu 
Published: September 2021

Abstract
There has been a growing interest in oil-water separation due to the massive economic and energy loss caused by world-wide oil spill. In the past decades, a new type of superhydrophobic surface has been developed for the efficient oil-water separation, but its large-scale use is significantly limited by its expensive, sophisticated, and fragile roughness structure. Meanwhile, to handle complex operating conditions, the transparency of the superhydrophobic surface has been more attractive due to its potential visual oil-water separation and optical applications. Herein, we showed a simple and versatile strategy to fabricate superhydrophobic coating with robustness and high transparency. Subsequently, this multifunctional superhydrophobic coating was utilized for oil-water separation and indicated excellent separation efficiency. In this strategy, candle soot composed of carbon nanoparticles was deposited onto the substrate and used as a rough surface template. Then, a filmy and hard silica shell was modified onto this template via chemical vapor deposition to reinforce the roughness structure. Following, this soot-silica coated substrate was calcined in air to remove the candle soot template. Finally, based on a rational surface design, this robust silica coating achieved excellent superhydrophobicity thereby showing inherently oil-water separation benefits. This reinforced superhydrophobic coating presented robust superhydrophobicity even after 410 s sand impacting with the height of 40 cm. Also, it retained excellent oil-water separation efficiency even after reuses.
Nonparametric Interrogation of Transcriptional Regulation in Single-Cell RNA and Chromatin Accessibility Multiomic Data
Authors: Harigaya Yuriko , Zhang Zhaojun , Zhang Hongpan , Zang Chongzhi , Zhang Nancy , Jiang Yuchao 
Published: September 2021

Abstract
Epigenetic control of gene expression is highly cell-type- and context-specific. Yet, despite its complexity, gene regulatory logic can be broken down into modular components consisting of a transcription factor (TF) activating or repressing the expression of a target gene through its binding to a cis-regulatory region. Recent advances in joint profiling of transcription and chromatin accessibility with single-cell resolution offer unprecedented opportunities to interrogate such regulatory logic. Here, we propose a nonparametric approach, TRIPOD, to detect and characterize three-way relationships between a TF, its target gene, and the accessibility of the TF’s binding site, using single-cell RNA and ATAC multiomic data. We apply TRIPOD to interrogate cell-type-specific regulatory logic in peripheral blood mononuclear cells and contrast our results to detections from enhancer databases, cis-eQTL studies, ChIP-seq experiments, and TF knockdown/knockout studies. We then apply TRIPOD to mouse embryonic brain data during neurogenesis and gliogenesis and identified known and novel putative regulatory relationships, validated by ChIP-seq and PLAC-seq. Finally, we demonstrate TRIPOD on SHARE-seq data of differentiating mouse hair follicle cells and identify lineage-specific regulation supported by histone marks for gene activation and super-enhancer annotations.
Optimization, purification and characterization of α-glucosidase inhibitors from Streptomyces costaricanus EBL.HB6 isolated in Vietnam
Authors: Nguyen Thi Trung , Phan Thi Hong Thao , Nguyen Phuong Dai Nguyen , Dao Thi Mai Anh , Mai Van Hien , Do Tuyen Thi 
Published: September 2021

Abstract
BackgroundDiabetes, a disease that has been a great burden of the treatment cost for patients and society. There are many drugs have been used to cure this disease available on the pharmaceutical market. One of the most prevalent source to produce these compounds are microorganism. Among them, Streptomyces sp. are popular microorganisms used for the production of α-glucosidase inhibitors (AGIs). Methods and ResultsIn this study, different cultivation conditions were optimized to enhance the production of AGIs. Purification and evaluation of AGIs from S. costaricanus EBL.HB6 were also performed. Our results demonstrated that Streptomyces costaricanus EBL.HB6 had the highest α-glucosidase inhibitory activity among 6 Streptomyces sp. strains were isolated in Vietnam. The 16S rRNA sequencing of isolating HBC6-2 indicated 99% identity to the corresponding sequence of Streptomyces costaricanus, and was registered on GenBank with the code MT 453944.1. Streptomyces costaricanus EBL.HB6 was able to produce melanin yellow pigment, and its aerial and substrate mycelia have brown and yellow-grey pigment on ISP2 cultivating medium, respectively. The α-glucosidase inhibitory activity of the supernatant was increased by a factor of 1.2 under optimal conditions (media containing 1.5% glucose, 1.2% yeast extract at 28°C, initial pH of 6.5, and culture time for 120 h) in comparison with the initial media and condition. The purified efficacy of a-glucosidase inhibitors was 5% with a retention factor of 0.71 on thin-layer chromatography and IC50 value of 9.59 mg/mL.ConclusionsStreptomyces costaricanus EBL.HB6 strain was selected, purified and evaluated for its highly producible of α-glucosidase inhibitors.