bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated Intravenous Administration of hiPSC-MSCs Enhance The Efficacy of Cell-Based Therapy In Tissue Regeneration
Authors: Sun Si-Jia , Dong Ming , Lai Wing-Hon , Ho Wai-In , Wei Rui , Liang Wei-Hao , Li Fei , Liao Song-Yan , Tse Hung-Fat
Published: September 2021

We sought to demonstrate whether therapeutic efficacy can be improved by combination of repeated intravenous administration and local transplantation of human induced pluripotential stem cell derived MSCs (hiPSC-MSCs). In this study, mice model of hind-limb ischemia was established by ligation of left femoral artery. hiPSC-MSCs (5x105) was intravenously administrated immediately after induction of hind limb ischemia with or without following intravenous administration of hiPSC-MSCs every week or every 3 days. Intramuscular transplantation of hiPSC-MSCs (3x106) was performed one week after induction of hind-limb ischemia. We compared the therapeutic efficacy and cell survival of intramuscular transplantation of hiPSC-MSCs with or without a single or repeated intravenous administration of hiPSC-MSCs. Repeated intravenous administration of hiPSC-MSCs could increase splenic regulatory T cells (Tregs) activation, decrease splenic natural killer (NK) cells expression, promote the polarization of M2 macrophages in the ischemic area and improved blood perfusion in the ischemic limbs. The improved therapeutic efficacy of MSC-based therapy was due to both increased engraftment of intramuscular transplanted hiPSC-MSCs and intravenous infused hiPSC-MSCs. In conclusion, our study supported a combination of repeated systemic infusion and local transplantation of hiPSC-MSCs for cardiovascular disease.
Clinicopathological Characteristics and Treatment Outcomes of Occult Breast Cancer: A Population-Based Study
Authors: Zhao Zijun , Zhang Ting , Yao Yu , Lu Xin
Published: September 2021

Background
Occult breast cancer (OBC) is a special type of breast cancer. It is defined as an axillary lymph node metastasis without ipsilateral breast malignancy according to mammogram and ultrasonography. Because of its rarity and no primary lesion, clinicopathological information is still insufficient, causing a controversial condition about its treatment recommendation. In this study, we aimed to clarify major clinicopathological information, treatment strategies and prognosis of OBC based on a large population.
Methods
We retrospectively collected adult female OBC population from Surveillance, Epidemiology, and End Results (SEER) database. We divided the whole OBC cohort into two groups based on surgical treatment. Descriptive analysis of 18 clinicopathological variables was conducted by Wilcoxin rank sum test, Chi-square and Fisher’s exact test. Survival analysis was performed in the whole cohort as well as based on different clinicopathological factors. Univariate and multivariate Cox regression analysis was performed to identify potential independent predictor for prognosis of OBC.
Results
1189 OBC patients was included in final analysis. Elderly patients predominated with a mean age of nearly 60. Most of the OBC patients were diagnosed as an early-stage carcinoma and ductal carcinoma took up nearly 40% of all the histological types of OBC. Luminal A is the commonest subtypes of OBC. For in-breast treatment, number of patients received mastectomy was 4 times more than that of patients received breast-conserving surgery (BCS). More than 70% patients receiving BCS took radiotherapy, significantly more than the portion of patients receiving radiation in mastectomy group (50.9%, P < 0.001). Median follow-up period of all subjects was about 62 months. 5-year and 10-year overall survival (OS) of the complete OBC cohort was 81.6% and 68.8%, respectively. No significant difference in OS and breast-cancer specific survival (BCSS) was found between mastectomy and BCS. Older age and larger number of positive lymph nodes causes a worse prognosis whereas radiotherapy brought a better clinical outcome for OBC patients.
Conclusion
OBC is a rare breast malignancy with a generally good prognosis. Less-intensive surgical intervention does not negatively impact clinical outcomes of OBC while additional radiotherapy is totally beneficial to prolong OS and BCSS.
Evolution of an Increased Performance Under Acute Challenge Does Not Exacerbate Vulnerability to Chronic Stress
Authors: Lipowska Małgorzata M. , Sadowska Edyta T. , Palme Rupert , Koteja Paweł
Published: September 2021

An adequate stress response plays a vital role in coping with challenges. However, if selection for improved coping with an acute challenge affects the entire stress response system, susceptibility to adverse effects of chronic stressors can be deepened. Here, we used bank voles from lines selected for high swim-induced aerobic metabolism (A) and unselected control (C), and asked if the selection affected sensitivity to chronic mild stress (CMS). The voles were first habituated to daily weighing and feces collection for three weeks, and then for two weeks were exposed to CMS or remained undisturbed. The habituation itself resulted in an increased swim-induced oxygen consumption in both line types, and a decreased body mass. The CMS treatment caused reduction of food consumption in the second week of the experiment, and, in males, a decline in the metabolic rate. Paradoxically, fecal corticosterone metabolites decreased in the CMS-treated group. The response to CMS did not differ between the line types. Thus, the selection for increased performance was not traded off by increased vulnerability to chronic stress. However, the unexpected decrease in corticosterone suggests that bank voles – and perhaps also other animals – prefer experiencing unpredictable, unpleasant stressors over the monotony of standard laboratory housing.
Learning Approaches Among Medical Undergraduates and Pre-Intern Doctors of A Selected University In Sri Lanka
Authors: Edirisinghe Sajith , De Silva Dulmini , Liyanage Indunil , Niluka Malith , Madushika Kasuni , Deegodagamage Sandeepani , Wijesundara Chanuka , Dissanayake Harsha , Yasawardene Surangi
Published: September 2021

Background
Medical education is constantly evolving to suit the changes in the field. It is a challenge to acquire the necessary knowledge, attitudes and skills within a limited time period in order to become a proficient doctor. This study aims to determine and compare the learning approaches (deep, strategic, superficial) used by medical undergraduates and pre-intern doctors.
Methods
Learning approaches of 138 pre-clinical medical undergraduates and pre-intern doctors of the University of Sri Jayewardenepura were assessed using the Approaches and Study Skills Inventory for Students (ASSIST) questionnaire. Data were analyzed using SPSS v-16 and Brown-Forsythe test.
Results
The strategic approach was identified as the predominant learning approach among 138 participants. One hundred and eight (108) participants (78.3%) used this method while 21 (15.2%) and 9 (6.5%) participants used the deep approach and the surface apathetic approach, respectively. Majority of both undergraduates [77.6% (83/107)] and pre-interns [80.6% (25/31)] used the strategic approach. This finding was also consistent between the 2 genders with a majority of males [69.6% (32/46)] as well as females [82.6% (76/92)] following the strategic approach. No significant difference in learning approaches was found to be present between undergraduate and pre-intern groups.
Conclusions
This study demonstrates that a majority of medical undergraduates and pre-intern doctors prefer the strategic learning approach. This implies that the medical curriculum has not adequately promoted the deep learning approach over the five-year period of studentship and this needs to be addressed in a subsequent curriculum change in order to promote a deep learning approach.
Ensemble of Nucleic Acid Absolute Quantitation Modules for Accurate Copy Number Variation Detection and Targeted RNA Profiling
Authors: Wu Lucia , Dai Peng , Wang Michael , Chen Sherry , Cohen Evan , Jayachandran Gitanjali , Zhang Jinny , Serrano Angela , Ueno Naoto , REUBEN JAMES , Barcenas Carlos , Zhang David
Published: September 2021

Current gold standard for absolute quantitation of a specific DNA sequence is droplet digital PCR (ddPCR), which has been applied to gene copy number variation (CNV) detection. However, the number of quantitation modules in ddPCR has been limited by fluorescence channels, which thus limits the CNV sensitivity due to sampling error following Poisson distribution. Here we develop a PCR-based molecular barcoding NGS approach, quantitative amplicon sequencing (QASeq), for accurate absolute quantitation which is compatible with high multiplexing to include over 200 quantitation modules. By attaching barcodes to individual target molecules with high efficiency, 2-plex QASeq exhibits higher and more consistent conversion yield than ddPCR in absolute molecule count quantitation. Multiplexed QASeq improves CNV sensitivity to allow confident distinguishment of 2.05 ploidy from normal 2.00 ploidy. We applied multiplexed QASeq to serial longitudinal plasma cfDNA samples from patients with metastatic ERBB2+ (HER2+) breast cancer seeking association with tumor progression. We further show an RNA QASeq panel for targeted expression profiling on a wide range of RNA samples including tumor formalin-fixed, paraffin-embedded (FFPE) RNA.
Association between Meibomian Gland Dysfunction and Depressive Symptoms: A Multi-center Cross-sectional Study
Authors: Wei Zhenyu , Liang Junqi , Cao Kai , Wang Leying , Baudouin Christophe , Labbé Antoine , Liang Qingfeng
Published: September 2021

Increased prevalence of depression has been found in patients with meibomian gland dysfunction (MGD); however, specific conditions of patients suffered from MGD and depression remains unclear. Our aim was to investigate the prevalence of depression in patients with MGD and analyze the risk factors of depression in MGD patients. In this multi-center cross-sectional study, we enrolled 830 MGD patients and 114 normal controls. Demographic information was collected by designed questionnaires about lifestyle habits, systemic and ocular medical history. Ophthalmic examinations were performed in a formal order. Depression symptoms were evaluated with a questionnaire survey using a modified self-rating depression scale (M-SDS). The correlations between the M-SDS score and demographic and clinical information were analyzed. The prevalence of hyperlipidemia and obstructive sleep apnea-hypopnea syndrome (OSAHS) was higher in the MGD group. There were 78 cases (9.4%) with depressive symptoms in the MGD group whereas there were 4 cases (3.5%) in controls. Similarly, M-SDS was higher in the MGD group. The characteristics of depression in the MGD group included: crying spells, sleep disturbance and depressed appetite. Some systemic diseases (OSAHS, allergy, skin disease) and the use of contact lenses was correlated with an increased risk of depressive symptoms in MGD patients.
NPR3 inhibits EMT and Tumour Metastasis of Human Osteosarcoma by Activating AKT/mTOR-mediated Autophagy
Authors: Yao Zhihong , Yang Yihao , Chen Jiaxiang , Chen Ting , Han Lei , Li Dongqi , Ye Lijuan , Zhu Yanan , Feng Yan , Wu Jia , Yu Xinchao , Yang Zuozhang
Published: September 2021

BackgroundOsteosarcoma is an aggressive primary malignant cancer of bone mainly occurring in adolescence with a characteristic of high metastasis and relapse rate. In our previous study, we first identified that NPR3 was significantly decreased in OS samples. Here, we purposed to investigate the effect and the possible mechanisms of NPR3 on the progression of human OS. MethodsThe expression of NPR3 in OS patients and cells was detected by qRT-PCR, and IHC analysis. The effect of the expression of NPR3 on tumour metastasis was examined in vitro and in vivo. The molecular mechanisms of the regulation of NPR3 were evaluated in vitro and in vivo. The clinical relevance of 5-year overall survival with the expression of NPR3 was evaluated in 294 patients with OS. ResultsFirstly, we indicated that NPR3 was substantially downregulated expression in OS tissues and cells by qRT-PCR and IHC assay. And the patients with lower expression of NPR3 have a poor prognosis. Functional studies revealed that over-expression of NPR3 inhibited the proliferation and invasion of cells. Meanwhile, over-expression of NPR3 markedly inhibited tumorigenesis and weakened tumour metastasis in vivo. Interestingly, we found that over-expression of NPR3 could induce autophagy, promote apoptosis and inhibit EMT. Additionally, overexpression of NPR3 decreased the phosphorylation levels of AKT and mTOR. Loss-of-function experiments displayed that effects of NPR3 were weakened by treatment with the specific autophagy inhibitor Baf-A1 and CQ. ConclusionsTaken together, these results demonstrated that down-regulation of NPR3 promote lung metastasis of human OS by promoting EMT in part through the AKT/mTOR mediated autophagy, suggesting that NPR3 has therapeutic potential for OS patients with metastasis.
Concept and design of extended hybrid laminar flow control suction panels
Authors: Traub Hendrik , Wolff Johannes , Jose Siby , Lobitz Lennart , Schollerer Martin , Hühne Christian
Published: September 2021

Fully laminar aircraft are one step towards reaching eco-efficient aviation. However, high system complexity and significant manufacturing effort prevent the wide usage of existing laminarisation concepts such as laminar flow control, which are rarely found in commercial aircraft. Hybrid laminar flow control concepts reduce the manufacturing effort significantly at the cost of only achieving partial laminar flow. This paper presents extended hybrid laminar flow control concepts for fully laminar wings, with reduced system complexity. A detailed study of structural and aerodynamic requirements provides the foundation for partial design solutions of active suction structures. The authors derive two concepts for active suction panels from the structural design space. While the first concept relies on state of the art manufacturing techniques, the focus of the second concept is on additive manufacturing technologies. Based on these concepts, it is feasible to design fully laminar wings with structurally integrated active suction systems. The authors propose an aerodynamic test strategy for further developing extended hybrid laminar flow control.
Internet Industry Data Openness and Personal Information Protection Based on Privacy Laws
Authors: Gao Yurong , Guo Yiping , Jumani Awais Khan , Shankar Achyut
Published: September 2021

Data security needs a comprehensive system design approach that combines legal, administrative, and technical protection. These laws generally contain complete rules and principles relevant to the collecting, storing, and using personal information in line with international standards on privacy and data protection. Personal data should be legally collected for a specified reason and not be used without authorization for unlawful monitoring or profiling by governments or third parties. In advocacy and open data activity, increasing attention has been placed on privacy problems. To secure the protection of this data, the Privacy Law (PL) and the Regulations typically put forth industrial and technical standards on IT systems that hold and handle personal data. Concerns about information privacy are genuine, valid, and exacerbated on the Internet of Things (IoT) and Cyber-Physical Systems (CPS). This article suggests that compliance with IoT and CPS Data Privacy (DP) at technical and non-technical levels should be dealt with. The proposed architecture is then coupled with a reference framework for the business architecture to offer a DP-IoT model focused on the industry and technology and positioned to comply with the Personal Information Protection Act (POPI). Therefore, methods are necessary to protect data privacy based on both system and organizational reference designs. In the end, users should have specific rights to information about them, including the capacity and method to seek recourse to protect such rights, to acquire and amend incorrect details. The DP-IoT model shows a privacy ratio of 92.6%, scalability ratio of 91.5, data management ratio of 94.3%, data protection ratio of 96.7%, customer satisfaction rate of 92.2 %, attack prevention ratio of 95.5% and energy consumption ratio of 25.5 % compared to the existing methods.
DOA-based Localization Using Deep Learning for Wireless Seismic Acquisition
Authors: Aliyu Kabiru N. , Alawsh Saleh A. , Muqaibel Ali H. , Al-Dharrab Suhail I. , Mesbah Wessam , Reddy Varun A. , Bazzi Ahmad , Stüber Gordon L.
Published: September 2021

Oil and gas companies consider transforming conventional cable-based seismic acquisition to wireless acquisition as a promising step for cost and weight reduction in reservoir exploration. Wireless seismic acquisition requires large number of wireless geophone (WG) sensors to be deployed in the field. The locations of the WG sensors must be known when processing the collected data. The application of direction of arrival (DOA) estimation helps in localizing WGs and improves received signal level through beam steering and interference avoidance. Conventional DOA algorithms require high computational complexity which renders them inefficient for real-time response. In this paper, deep neural network (DNN) is proposed for DOA estimation of WGs at wireless gateway node (WGN) under different channel conditions. The estimated angle and corresponding coordinates of WGNs are used in least square estimation (LSE) to estimate the position of the WGs. The simulation results depict reasonable estimation and position accuracy in real-time.
Risk of Airway Fire with the use of KTP Laser and High Flow Humidified Oxygen Delivery in a Laryngeal Surgery Model
Authors: Huang Lucy , Badenoch Adam , Vermeulen Marthinus , Ullah Shahid , Woods Charmaine , Athanasiadis Theodore , Ooi Eng Hooi
Published: September 2021

Background Airway surgery presents a unique environment for operating room fire to occur. This study aims to explore the factors of combustion when using KTP laser with high flow oxygen in an ex-vivo model. MethodsThe variables tested were varying tissue type, tissue condition, oxygen concentration, laser setting, and smoke evacuation in a stainless-steel model. Outcome measures were time of lasing to the first spark and/or flame. A multivariate Cox proportional hazard model was used to determine the risk of spark and flame across the different risk factors. ResultsFor every 10% increase in oxygen concentration above 60% the risk of flame increased by a factor of 2.3. Continuous laser setting at 2.6W increased the risk by a factor of 72.8. The risk of lasing adipose tissue is 7.3 times higher than that of muscle. Charred tissue increases the risk of flame by a factor of 92.8. Flame occurred without a preceding spark 93.6% of the time. Conclusions Using KTP laser in the pulsed mode with low wattages, minimising lasing time, reducing the oxygen concentration and avoiding lasing adipose or charred tissue produce a relatively low estimated risk of spark or flame.
Tumor-Derived Biomimetic Nanozyme With Immune Evasion Ability For Synergistically Enhanced Low Dose Radiotherapy
Authors: Huang Chunyu , Liu Zeming , Chen Mingzhu , Du Liang , Zheng Yongfa , Liu Wei
Published: September 2021

High doses of radiation can cause serious side effects and drug resistance, high-performance radiosensitizers are urgently needed. To overcome this issue, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for use in combination with low-dose RT. CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH) and peroxidase activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2Gy) can provide a substantial suppression of tumor proliferation. To summarize, this is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.
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

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

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

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

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

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

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

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

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

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

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

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.
Longitudinal Surface Measurements of Human Blastocysts Show That the Dynamics of Blastocoel Expansion Are Associated With Fertilization Method and Ongoing Pregnancy
Authors: Marion Eva Sophie van , Chavli Effrosyni A. , Laven Joop S.E. , Steegers-Theunissen Régine P.M. , Koster Maria P.H. , Baart Esther B.
Published: September 2021

Background: Despite all research efforts during this era of novel time-lapse morphokinetic parameters, a morphological grading system is still routinely being used for embryo selection at the blastocyst stage. The blastocyst expansion grade, as evaluated during morphological assessment, is associated with clinical pregnancy. However, this assessment is performed without taking the dynamics of blastocoel expansion into account. Here, we studied the dynamics of blastocoel expansion by comparing longitudinal blastocoel surface measurements using time-lapse embryo culture. Our aim was to first assess if this is impacted by fertilization method and second, to study if an association exists between these measurement and ongoing pregnancy. Methods: This was a retrospective cohort study including 225 couples undergoing 225 cycles of in vitro fertilization (IVF) treatment with time-lapse embryo culture. The fertilization method was either conventional IVF, intracytoplasmic sperm injection (ICSI) with ejaculated sperm or ICSI with sperm derived from testicular sperm extraction (TESE-ICSI). This resulted in 289 IVF embryos, 218 ICSI embryos and 259 TESE-ICSI embryos that reached at least the full blastocyst stage. Blastocoel surface measurements were performed on time-lapse images every hour, starting from full blastocyst formation (tB). Linear mixed model analysis was performed to study the association between blastocoel expansion, the calculated expansion rate (µm2/hour) and both fertilization method and ongoing pregnancy. Results: The blastocoel of both TESE-ICSI embryos and ejaculated sperm ICSI embryos was significantly smaller than the blastocoel of IVF embryos (beta -647.7 µm2; 95% confidence interval (CI): -1133.6 to -161.9, beta -1017.0 µm2; 95% CI: -1525.1 to -508.8, respectively). In addition, the blastocoel of embryos resulting in an ongoing pregnancy was significantly larger (beta 795.4 µm2; 95% CI: 15.4 to 1575.4) and expanded significantly faster (beta 100.9 µm2/hour; 95% CI: 5.7 to 196.2) than the blastocoel of embryos that did not result in an ongoing pregnancy. Conclusion: Longitudinal blastocyst surface measurements and expansion rates are promising non-invasive quantitative markers that can aid the embryo selection for transfer and cryopreservation.
Displacement and Stress Distribution of the Craniomaxillofacial Complex Under Different Surgical Conditions: A Three-Dimensional Finite Element Analysis of Fracture Mechanics
Authors: Chen Junjie , Xu Yuhan , Li Chengri , Zhang Lingling , Yi Fang , Lu Yanqin
Published: September 2021

Objective: To provide a simplified treatment strategy for patients with maxillary transverse deficiency. We investigated and compared the fracture mechanics and stress distribution of a midline palatal suture under dynamic loads during surgically-assisted rapid palatal expansion. Methods: Based on the cone-beam computed tomography (CBCT) data of a 21-year-old female volunteer, a three-dimensional model of the cranio-maxillofacial complex (including the palatal suture) was constructed. A finite element analysis model was constructed based on meshwork. After the yield strength of the palatal suture was set, an increasing expansion force (0–500 N) was applied within 140 ms to calculate the time–load curve, which mimicked nonsurgical bone expansion (model A). The same method was used to evaluate the fracture process, time and stress distribution of the palatal suture in maxillary lateral osteotomy-assisted (model B) and LeFort osteomy I (LFIO)-assisted expansion of the maxillary arch (model C). Results: Compared with model A, the palatal suture of model B and model C showed a faster stress accumulation rate and shorter fracture time, and the fracture time of model B and model C was almost identical. Compared with model A, we discovered that model B and model C showed greater lateral extension of the maxilla, and the difference was reflected mainly in the lower part of the maxilla, and there was no difference between model B and model C in lateral extension of the maxilla. Conclusions: Compared with arch expansion using nonsurgical assistance (model A), arch expansion using maxillary lateral wall-osteotomy (model B) or LFIO had a faster rate of stress accumulation, shorter time of fracture of the palatal suture and increased lateral displacement of the maxilla. Compared with arch expansion using LFIO (model C), arch expansion using lateral osteotomy (model B) had a similar duration of palatal suture rupture and lateral maxillary extension. In view of the trauma and serious complications associated with LFIO, maxillary lateral wall-osteotomy could be considered a substitute for LFIO.