bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation and Functional Complexity of the Chlorophyll-Binding Protein IsiA
Authors: Jia Anqi , Zheng Yanli , Chen Hui , Wang Qiang
Published: November 2021

As the oldest known lineage of oxygen-releasing photosynthetic organisms, cyanobacteria play the key roles in helping shaping the ecology of Earth. Iron is an ideal transition metal for redox reactions in biological systems. Cyanobacteria frequently encounter iron deficiency due to the environmental oxidation of ferrous ions to ferric ions, which are highly insoluble at physiological pH. A series of responses, including architectural changes to the photosynthetic membranes, allow cyanobacteria to withstand this condition and maintain photosynthesis. Iron-stress-induced protein A (IsiA) is homologous to the cyanobacterial chlorophyll (Chl)-binding protein, photosystem II core antenna protein CP43. IsiA is the major Chl-containing protein in iron-starved cyanobacteria, binding up to 50% of the Chl in these cells, and this Chl can be released from IsiA for the reconstruction of photosystems during the recovery from iron limitation. The pigment–protein complex (CPVI-4) encoded by isiA was identified and found to be expressed under iron-deficient conditions nearly 30years ago. However, its precise function is unknown, partially due to its complex regulation; isiA expression is induced by various types of stresses and abnormal physiological states besides iron deficiency. Furthermore, IsiA forms a range of complexes that perform different functions. In this article, we describe progress in understanding the regulation and functions of IsiA based on laboratory research using model cyanobacteria.
Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer
Authors: Yi Kezhen , Liu JingChong , Rong Yuan , Wang Cheng , Tang Xuan , Zhang XiaoPing , Xiong Yunhe , Wang Fubing
Published: November 2021

Background: Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40–80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer.

Methods: We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas and analyzed differentially expressed genes based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology functions. On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curvevalidation were then performed. Risk curves and nomograms were generated for both groups to predict survival. Finally, RT-qPCR was applied to analyze gene expression.

Results: Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, and JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues.

Conclusion: This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.
Large-Scale Functional Networks, Cognition and Brain Structures Supporting Social Cognition and Theory of Mind Performance in Prodromal to Mild Alzheimer’s Disease
Authors: Valera-Bermejo Jose Manuel , De Marco Matteo , Mitolo Micaela , Cerami Chiara , Dodich Alessandra , Venneri Annalena
Published: November 2021

Impairment of social cognition (SC) skills such as recognition and attribution of intentions and affective states of others (Theory of Mind, ToM) has been evidenced in Alzheimer’s Disease (AD). This study investigated the neuropsychological, neuroanatomical and brain-functional underpinnings of SC processing to obtain an understanding of the social neurophenotype in early probable AD. Forty-six patients with mild cognitive impairment and mild probable AD underwent SC assessment including emotion recognition (Ekman-60-faces task) and cognitive and affective ToM (Reading-the-Mind-in-the-Eyes test and Story-based Empathy task). Linear models tested the association between SC scores and neuropsychological measures, grey matter maps and large-scale functional networks activity. The executive domain had the most predominant association with SC scores in the cognitive profile. Grey matter volume of the anterior cingulate, orbitofrontal, temporoparietal junction (TPJ), superior temporal, and cerebellar cortices were associated with ToM. Social cognition scores were associated with lower connectivity of the default-mode network with the prefrontal cortex. The right fronto-parietal network displayed higher inter-network connectivity in the right TPJ and insula while the salience network showed lower inter-network connectivity with the left TPJ and insula. Connectivity coupling alterations of executive-attentional networks may support default mode social-cognitive-associated decline through the recruitment of frontal executive mechanisms.
Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders
Authors: Hu Banglian , Duan Shengshun , Wang Ziwei , Li Xin , Zhou Yuhang , Zhang Xian , Zhang Yun-Wu , Xu Huaxi , Zheng Honghua
Published: November 2021

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.
An Advanced Transcriptional Response to Corticosterone After Single Prolonged Stress in Male Rats
Authors: Ding Jinlan , Chen Xinzhao , Han Fang , Meijer Onno C.
Published: November 2021

Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes (t = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.
Ir76b is a Co-receptor for Amine Responses in Drosophila Olfactory Neurons
Authors: Vulpe Alina , Menuz Karen
Published: November 2021

Two large families of olfactory receptors, the Odorant Receptors (ORs) and Ionotropic Receptors (IRs), mediate responses to most odors in the insect olfactory system. Individual odorant binding “tuning” OrX receptors are expressed by olfactory neurons in basiconic and trichoid sensilla and require the co-receptor Orco. The situation for IRs is more complex. Different tuning IrX receptors are expressed by olfactory neurons in coeloconic sensilla and rely on either the Ir25a or Ir8a co-receptors; some evidence suggests that Ir76b may also act as a co-receptor, but its function has not been systematically examined. Surprisingly, recent data indicate that nearly all coeloconic olfactory neurons co-express Ir25a, Ir8a, and Ir76b. Here, we demonstrate that Ir76b and Ir25a function together in all amine-sensing olfactory receptor neurons. In most neurons, loss of either co-receptor abolishes amine responses. In contrast, amine responses persist in the absence of Ir76b or Ir25a in ac1 sensilla but are lost in a double mutant. We show that responses mediated by acid-sensing neurons do not require Ir76b, despite their expression of this co-receptor. Our study also demonstrates that one population of coeloconic olfactory neurons exhibits Ir76b/Ir25a-dependent and Orco-dependent responses to distinct odorants. Together, our data establish the role of Ir76b as a bona fide co-receptor, which acts in partnership with Ir25a. Given that these co-receptors are among the most highly conserved olfactory receptors and are often co-expressed in chemosensory neurons, our data suggest Ir76b and Ir25a also work in tandem in other insects.
Comparison of Gait Speed Reserve, Usual Gait Speed, and Maximum Gait Speed of Adults Aged 50+ in Ireland Using Explainable Machine Learning
Authors: Davis James R. C , Knight Silvin P. , Donoghue Orna A. , Hernández Belinda , Rizzo Rossella , Kenny Rose Anne , Romero-Ortuno Roman
Published: November 2021

Gait speed is a measure of general fitness. Changing from usual (UGS) to maximum (MGS) gait speed requires coordinated action of many body systems. Gait speed reserve (GSR) is defined as MGS–UGS. From a shortlist of 88 features across five categories including sociodemographic, cognitive, and physiological, we aimed to find and compare the sets of predictors that best describe UGS, MGS, and GSR. For this, we leveraged data from 3,925 adults aged 50+ from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). Features were selected by a histogram gradient boosting regression-based stepwise feature selection pipeline. Each model’s feature importance and input–output relationships were explored using TreeExplainer from the Shapely Additive Explanations explainable machine learning package. The mean Radj2 (SD) from fivefold cross-validation on training data and the Radj2 score on test data were 0.38 (0.04) and 0.41 for UGS, 0.45 (0.04) and 0.46 for MGS, and 0.19 (0.02) and 0.21 for GSR. Each model selected features across all categories. Features common to all models were age, grip strength, chair stands time, mean motor reaction time, and height. Exclusive to UGS and MGS were educational attainment, fear of falling, Montreal cognitive assessment errors, and orthostatic intolerance. Exclusive to MGS and GSR were body mass index (BMI), and number of medications. No features were selected exclusively for UGS and GSR. Features unique to UGS were resting-state pulse interval, Center for Epidemiologic Studies Depression Scale (CESD) depression, sit-to-stand difference in diastolic blood pressure, and left visual acuity. Unique to MGS were standard deviation in sustained attention to response task times, resting-state heart rate, smoking status, total heartbeat power during paced breathing, and visual acuity. Unique to GSR were accuracy proportion in a sound-induced flash illusion test, Mini-mental State Examination errors, and number of cardiovascular conditions. No interactions were present in the GSR model. The four features that overall gave the most impactful interactions in the UGS and MGS models were age, chair stands time, grip strength, and BMI. These findings may help provide new insights into the multisystem predictors of gait speed and gait speed reserve in older adults and support a network physiology approach to their study.
A Survey of Hesitancy and Response to the COVID-19 Vaccine Among Patients With Epilepsy in Northeast China
Authors: Li Nan , Chu Chaojia , Lin Weihong
Published: November 2021

Objective: This study was conducted to investigate the hesitancy and response of people with epilepsy (PWE) to the coronavirus disease 2019 (COVID-19) vaccine.

Methods: We conducted an online survey among PWE in northeast China about hesitancy and response to the COVID-19 vaccine. Their demographic background and symptomatic data about epilepsy were also recorded, and we analyzed the epilepsy-related risk factors in delaying the vaccine.

Results: In total, 357 patients with confirmed epilepsy were included in the survey, and only 38 (11%) patients received the COVID-19 vaccine. Fear of aggravating epilepsy (58%, n = 185), discouragement from health workers for epilepsy (22%, n = 70), and fear of patients of other unknown serious side effects (13%, n = 42) were the main reasons for delaying vaccination. A higher seizure frequency was the only epilepsy-related risk factor in delaying the vaccine (OR = 1.104, 95% CI: 0.988–1.233). None of the vaccinated patients reported that the vaccine aggravated their epilepsy.

Significance: Understanding concerns about the COVID-19 vaccine among PWE could help to improve health education and promote the establishment of an immune barrier.
Selenotranscriptome Network in Non-alcoholic Fatty Liver Disease
Authors: Day Kaitlin , Seale Lucia A. , Graham Ross M. , Cardoso Barbara R.
Published: November 2021

Observational studies indicate that selenium may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Transcriptomic exploration of the aetiology and progression of NAFLD may offer insight into the role selenium plays in this disease. This study compared gene expression levels of known selenoprotein pathways between individuals with a healthy liver to those with NAFLD. Publicly available gene expression databases were searched for studies that measured global gene expression in liver samples from patients with steatosis and non-alcoholic steatohepatitis (NASH) and healthy controls (with [HOC] or without [HC] obesity). A subset of five selenoprotein-related pathways (164 genes) were assessed in the four datasets included in this analysis. The gene TXNRD3 was less expressed in both disease groups when compared with HOC. SCLY and SELENOO were less expressed in NASH when compared with HC. SELENOM, DIO1, GPX2, and GPX3 were highly expressed in NASH when compared to HOC. Disease groups had lower expression of iron-associated transporters and higher expression of ferritin-encoding sub-units, consistent with dysregulation of iron metabolism often observed in NAFLD. Our bioinformatics analysis suggests that the NAFLD liver may have lower selenium levels than a disease-free liver, which may be associated with a disrupted iron metabolism. Our findings indicate that gene expression variation may be associated with the progressive risk of NAFLD.
Food Processing and Phthalate Exposure: The Nutrition and Health Survey in Taiwan (1993–1996 and 2005–2008)
Authors: Huang Yi-Chen , Huang Pei-Ru , Lo Yuan-Ting C. , Sun Chien-Wen , Pan Wen-Harn , Wang Shu-Li , Huang Han-Bin
Published: November 2021

Background: Phthalates esters are widely used commercially and can leach from a food container or food packaging. Few studies have been conducted in Asia regarding food processed to varying levels and human phthalate exposure. This study aimed to evaluate the association between unprocessed and ultra-processed food intake and urinary phthalate metabolite levels in the Taiwanese adult population.

Methods: A total of 516 participant data were extracted from the cross-sectional 1993–1996 and 2005–2008 Nutrition and Health Survey in Taiwan of those aged over 18 years, where urinary measures and one 24-h dietary recall were collected. Urinary concentrations of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, and di-(2-ethylhexyl) phthalate metabolites including monomethyl phthalate, monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate, mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were measured in spot urine samples. The NOVA food processing classification system was applied to divide all consumed foods into four mutually exclusive groups including unprocessed or minimally processed, processed culinary ingredients, processed and ultra-processed food. Generalized linear models were employed to examine the associations between the percentage quartiles (Qs) of unprocessed and ultra-processed foods in the total weight of food and the urinary phthalate metabolites.

Results: Compared with participants in the lowest quartiles (Q1) of ultra-processed food intake, highest ultra-processed food intake (Q4) had 65.7% (95% confidence interval [CI]: 4.83, 162) higher urinary concentrations of MEP after adjusted for covariates. In contrast, the higher unprocessed food consumption was inversely associated with urinary concentrations of MEP and MBP (P for trend = 0.03). When compared to the lowest unprocessed food consumers (Q1), higher consumers (Q4) presented 38.6% (95% CI: −61.3, −2.59) lower MEP concentrations and 23.1% (95% CI: −38.5, −3.71) lower MBP concentrations.

Conclusion: Ultra-processed food consumption was associated with increased concentrations of urinary MEP. Conversely, consuming unprocessed food was associated with lower concentrations of MEP and MBP in the Asian Taiwanese adult population.
RETRACTED: LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8
Authors: Su Changlei , Huang Kejin
Published: November 2021

This study aimed to investigate the carcinogenic role of long non-coding RNA T-cell factor 7 (lnc-TCF7) in epithelial ovarian cancer (EOC). Lnc-TCF7 overexpression and shRNA plasmids were transfected into SKOV3 and OVCAR3 cells, followed by measurement of cell proliferation, migration, invasion, apoptosis, stemness, and mRNA profile (via microarray). Besides, lnc-TCF7 expression was measured in tumor and adjacent tissues from 76 EOC patients. Lnc-TCF7 was upregulated in EOC cell lines; its overexpression increased cell proliferation, migration, invasion, but decreased apoptosis and promoted CD44, CD133 expressions, CD44+CD133+ cell proportion, spheres formation efficiency and drug resistance to cisplatin in SKOV3 and OVCAR3 cells. Besides, lnc-TCF7 ShRNA exhibited opposite effects comparing with its overexpression. Microarray analysis revealed 267 mRNAs were modulated by lnc-TCF7 dysregulation, among which ITGB8 was the most dysregulated one, which was validated by subsequent western blot and RT-qPCR. Furthermore, ITGB8 overexpression not only induced proliferation, migration, invasion and stemness, but also attenuated the effect of lnc-TCF7 ShRNA on these functions in SKOV3 and OVCAR3 cells. In addition, lnc-TCF7 was upregulated in tumor tissues and correlated with higher pathological grade, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and worse overall survival in EOC patients. Conclusively, lnc-TCF7 regulates multiple oncogenic pathways, promotes proliferation, migration, invasion, stemness via upregulating ITGB8. It also correlates with advanced tumor features and poor prognosis in EOC, implying its potential as a target for EOC treatment.
Atypical Chronic Myelogenous Leukemia, BCR-ABL1 Negative: Diagnostic Criteria and Treatment Approaches
Authors: Diamantopoulos Panagiotis T. , Viniou Nora-Athina
Published: November 2021

Atypical chronic myelogenous leukemia (aCML), BCR/ABL1 negative is a rare myelodysplastic/myeloproliferative neoplasm, usually manifested with hyperleukocytosis without monocytosis or basophilia, organomegaly, and marked dysgranulopoiesis. In this review, we will discuss the classification and diagnostic criteria of aCML, as these have been formulated during the past 30 years, with a focus on the recent advances in the molecular characterization of the disease. Although this entity does not have a definitive molecular profile, its molecular characterization has contributed to a better understanding and more accurate classification and diagnosis of aCML. At the same time, it has facilitated the identification of adverse prognostic factors and the stratification of patients according to their risk for leukemic transformation. What is more, the molecular characterization of the disease has expanded our therapeutic choices, thoroughly presented and analyzed in this review article.
Successful BCMA CAR-T Therapy for Multiple Myeloma With Central Nervous System Involvement Manifesting as Cauda Equina Syndrome—A Wandering Road to Remission
Authors: Wang Yiyun , Wang Linqin , Zeng Yifan , Hong Ruimin , Zu Cheng , Yin Elaine Tan Su , Zhao Houli , Wei Guoqing , Yang Li , Jin Aiyun , Hu Yongxian , Huang He
Published: November 2021

Multiple myeloma (MM) with central nervous system (CNS) involvement is rare with only 1% incidence. So far, there is no standard or effective treatment for CNS MM, and the expected survival time is fewer than 6 months. Here, we report a case of MM with CNS involvement presented with cauda equina syndrome (CES) who achieved complete remission after anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy (Chictr.org.cn, ChiCTR1800017404). The expansion of BCMA CAR-T cells was observed in both peripheral blood (PB) and cerebrospinal fluid (CSF). The CAR-T cells peaked at 2.4 × 106/l in CSF at day 8 and 4.1 × 109/l in PB at day 13. The peak concentration of interleukin (IL)-6 in CSF was detected 3 days earlier, and almost five times higher than that in PB. Next, morphological analysis confirmed the elimination of nucleated cells in CSF 1 month after CAR-T cell treatment from 300 cells/μl, and the patient achieved functional recovery with regressed lesion shown in PET-CT. The case demonstrated that BCMA CAR-T cells are effective and safe in this patient population.
Race-Related Differences Between and Within Sex to Experimental Thermal Pain in Middle and Older Adulthood: An Exploratory Pilot Analysis
Authors: Moss Karen O. , Wright Kathy D. , Tan Alai , Rose Karen M. , Scharre Douglas W. , Gure Tanya R. , Cowan Ronald L. , Failla Michelle D. , Monroe Todd B.
Published: November 2021

This brief report details a pilot analysis conducted to explore racial differences in pain sensitivity and unpleasantness between cognitively healthy Black and White adults, stratified by sex. A total of 24 cognitively healthy adults (12 Black and 12 White) from two completed studies were matched by age and sex, and divided into two groups based on race. Stratified analyses by sex demonstrated that Black females reported experiencing pain intensity ratings of all three intensity sensations at lower temperatures than White females. These findings will inform future research studies to determine if these results hold true in a fully-powered sample and should include mixed methodologies, incorporating neuroimaging data to further assess this phenomenon. Improving pain assessment and management across racial/ethnic groups will help healthcare providers such as nurses and physicians to ensure optimal quality of life for all.
Sexual Function in Men Living With a Fontan Circulation
Authors: Rubenis Imants , Tran Derek , Bullock Andrew , Wijesekera Vishva , Baker David , d'Udekem Yves , du Plessis Karin , Katz Darren , Lowy Michael , Zentner Dominica , Celermajer David , Cordina Rachael
Published: November 2021

Introduction: It is unknown if the Fontan circulation has an impact on sexual health in men. This study assessed self-reported sexual health and fertility in men with a Fontan circulation.

Aims: In this prospective, cross-sectional study, Australian men ≥18 years enrolled in the Fontan Registry of Australia and New Zealand were invited to complete the International Index of Erectile Function (IIEF), alongside questions assessing fertility. These data were compared to historical, age-matched controls.

Results: Of 227 eligible men, 54 completed the survey; of those 37 were sexually active and included in the final analysis. Mean age was 28 ± 3 years, age at Fontan was 5 ± 3 years. Fontan type was extra-cardiac conduit in 15 (41%), lateral tunnel in 12 (32%), and atriopulmonary connection (APC) in 10 (27%). Ventricular function was normal in 24 (83%), and all were New York Heart Association Class I (23 patients, 79%) and II (six patients, 21%). Nine participants (24%) had erectile dysfunction (IIEF-EF score ≤25). The severity was mild (IIEF 22–24) in six (16%), mild–moderate (IIEF 17–21) in two (5%), and moderate (IIEF 11–16) in one (3%). Baseline characteristics and current medication usage were similar in those with and without erectile dysfunction. Compared with historical control values, erectile function was not significantly impaired in the Fontan population (p =0.76). Men with a Fontan circulation had decreased levels of sexual desire and overall satisfaction (p < 0.001). There was no correlation between the presence of erectile dysfunction and any assessed parameter. Eleven (30%) of the cohort reported a pregnancy with a prior partner.

Conclusion: In our cohort, overall erectile function was comparable between men with a Fontan circulation and historical controls, however sexual desire and overall satisfaction were reduced. There was no correlation between study parameters and the presence of erectile dysfunction. The proportion of the cohort who had a prior pregnancy was congruent with population data.
Alginate-Capped Silver Nanoparticles as a Potent Anti-mycobacterial Agent Against Mycobacterium tuberculosis
Authors: Chen Cheng-Cheung , Chen Yih-Yuan , Yeh Chang-Ching , Hsu Chia-Wei , Yu Shang-Jie , Hsu Chih-Hao , Wei Ting-Chun , Ho Sin-Ni , Tsai Pei-Chu , Song Yung-Deng , Yen Hui-Ju , Chen Xin-An , Young Jenn-Jong , Chuang Chuan-Chung , Dou Horng-Yunn
Published: November 2021

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.
Evaluation of the Direct Costs of Managing Adverse Drug Events in all Ages and of Avoidable Adverse Drug Events in Older Adults in Japan
Authors: Katsuno Hayato , Tachi Tomoya , Matsuyama Takuya , Sugioka Mayuko , Aoyama Satoshi , Osawa Tomohiro , Noguchi Yoshihiro , Yasuda Masahiro , Goto Chitoshi , Mizui Takashi , Teramachi Hitomi
Published: November 2021

In Japan, medical costs are increasing annually, and the increase in national medical costs, particularly in the direct cost of managing adverse drug events, is high. An in-depth understanding of these costs is important for their reduction. This study aimed to calculate the direct cost of managing adverse drug events in all ages, including older adults, and that of avoidable adverse drug events in older adults. We conducted a retrospective survey on patients aged 1 year or older who visited Gifu Municipal Hospital in Japan. We investigated and calculated the direct cost of managing adverse drug events and that of avoidable adverse drug events based on the Beers Criteria Japanese version (BCJ) and “Guidelines for medical treatment and its safety in the elderly 2015” (GMTSE-2015) in inpatients and outpatients. Among 6,504 patients, 11.1% visited the hospital or were hospitalized due to adverse drug events. The direct costs per patient with adverse drug events were 21,281 and 22,590 yen (166 and 176 euros as on September 13, 2021) for outpatients, and 853,175 and 874,582 yen (6,648 and 6,815 euros) for inpatients of all ages and older adults, respectively. The direct costs of avoidable adverse drug events per patient using drugs listed in the BCJ and GMTSE-2015 for older adults were 3,212 and 3,341 yen (25 and 26 euros) for outpatients, and 55,548 and 80,246 yen (433 and 625 euros) for inpatients, respectively. In sum, considering both inpatients and outpatients in the whole country, the direct costs of managing adverse drug events were 804.53 billion and 597.19 billion yen (6,269 million and 4,653 million euros) per year for all ages and older ages, respectively. The direct cost of avoidable adverse drug events in older adults was 83.43–258.44 billion yen (650–2,013 million euros) per year. We found that, in Japan, high medical costs are often caused by managing adverse drug events, and that the costs of avoidable adverse drug events in older adults based on the BCJ and GMTSE-2015 account for a substantial proportion of the medical cost. Therefore, by using the BCJ and GMTSE-2015, avoiding adverse drug events and reducing medical costs may be possible.
Blood Plasma Proteins Associated With Heart Rate Variability in Cosmonauts Who Have Completed Long-Duration Space Missions
Authors: Pastushkova Ludmila Kh. , Rusanov Vasily B. , Goncharova Anna G. , Nosovskiy Andrei M. , Luchitskaya Elena S. , Kashirina Daria N. , Kononikhin Alexey S. , Kussmaul Anna R. , Yakhya Yusef D. , Larina Irina M. , Nikolaev Evgeny N.
Published: November 2021

The study presents the results of evaluating the changes in the concentrations of blood plasma proteins associated with heart rate variability (HRV) in cosmonauts who have completed space missions lasting about 6months. The concentrations of 125 proteins were quantified in biological samples of the cosmonauts’ blood plasma. The subgroups of proteins associated with the physiological processes of the HRV autonomic regulation were identified using bioinformatic resources (Immunoglobulin heavy constant mu, Complement C1q subcomponent subunit C, Plasma serine protease inhibitor, Protein-72kDa type IV collagenase, Fibulin-1, Immunoglobulin lambda constant 3). The concentration of these proteins in the blood plasma before the flight, and the dynamics of concentration changes on the 1st and 7th days of the post-flight rehabilitation period differed in the groups of cosmonauts with a predominance of sympathetic or parasympathetic modulating autonomous influences. The dynamics of changes in the concentrations of the identified set of proteins reveal that in cosmonauts with a predominance of sympathetic modulating influences, the mechanisms of autonomic regulation are exposed to significant stress in the recovery period immediately after the completion of the space mission, compared with the cosmonauts with a predominance of parasympathetic modulating influences.
Culex quinquefasciatus Late Trypsin Biosynthesis Is Translationally Regulated by Trypsin Modulating Oostatic Factor
Authors: Borovsky Dov , Verhaert Peter , Rougé Pierre , Powell Charles A. , De Loof Arnold
Published: November 2021

Trypsin is a serine protease that is synthesized by the gut epithelial cells of female mosquitoes; it is the enzyme that digests the blood meal. To study its molecular regulation, Culex quinquefasciatus late trypsin was purified by diethylaminoethyl (DEAE), affinity, and C18 reverse-phase high performance liquid chromatography (HPLC) steps, and the N-terminal amino acid sequence was determined for molecular cloning. Five overlapping segments of the late trypsin cDNA were amplified by PCR, cloned, and the full sequence (855 bp) was characterized. Three-dimensional models of the pro-trypsin and activated trypsin were built and compared with other trypsin models. Trypsin modulating oostatic factor (TMOF) concentrations in the hemolymph were determined by ELISA and compared with trypsin activity in the gut after the blood meal. The results showed that there was an increase in TMOF concentrations circulating in the hemolymph which has correlated to the reduction of trypsin activity in the mosquito gut. Northern blot analysis of the trypsin transcripts after the blood meal indicated that trypsin activity also followed the increase and decrease of the trypsin transcript. Injections of different amounts of TMOF (0.025 to 50 μg) decreased the amounts of trypsin in the gut. However, Northern blot analysis showed that TMOF injections did not cause a decrease in trypsin transcript abundance, indicating that TMOF probably affected trypsin translation.
The Influence of Entrepreneurial Education and Psychological Capital on Entrepreneurial Behavior Among College Students
Authors: Cui Jun
Published: November 2021

This research investigated the influence of entrepreneurial education (EE) on entrepreneurial behavior (EB) through psychological capital (PC). A cross-section survey data of 1,405 college students in China were used to test the proposed hypothesis based on human capital theory and PC literature. The research found that EE had direct effects on EB and on all four sub-constructs (hope, self-efficacy, resilience, and optimism) of PC, and that only self-efficacy positively correlated with EB and mediated the relationship between EE and EB while the other three components of PC did not. These findings contribute to the understanding of both educational and psychological effects on EB. The study also has practical implications for policymakers, managers, and educators in entrepreneurial education.
Psychological Network Analysis of General Self-Efficacy in High vs. Low Resilient Functioning Healthy Adults
Authors: Schueler Katja , Fritz Jessica , Dorfschmidt Lena , van Harmelen Anne-Laura , Stroemer Eike , Wessa Michèle
Published: November 2021

Resilience to stress has gained increasing interest by researchers from the field of mental health and illness and some recent studies have investigated resilience from a network perspective. General self-efficacy constitutes an important resilience factor. High levels of self-efficacy have shown to promote resilience by serving as a stress buffer. However, little is known about the role of network connectivity of self-efficacy in the context of stress resilience. The present study aims at filling this gap by using psychological network analysis to study self-efficacy and resilience. Based on individual resilient functioning scores, we divided a sample of 875 mentally healthy adults into a high and low resilient functioning group. To compute these scores, we applied a novel approach based on Partial Least Squares Regression on self-reported stress and mental health measures. Separately for both groups, we then estimated regularized partial correlation networks of a ten-item self-efficacy questionnaire. We compared three different global connectivity measures–strength, expected influence, and shortest path length–as well as absolute levels of self-efficacy between the groups. Our results supported our hypothesis that stronger network connectivity of self-efficacy would be present in the highly resilient functioning group compared to the low resilient functioning group. In addition, the former showed higher absolute levels of general self-efficacy. Future research could consider using partial least squares regression to quantify resilient functioning to stress and to study the association between network connectivity and resilient functioning in other resilience factors.
The Biopsychosocial Model and Perinatal Health Care: Determinants of Perinatal Care in a Community Sample
Authors: Duberstein Zoe T. , Brunner Jessica , Panisch Lisa S. , Bandyopadhyay Sanjukta , Irvine Carrie , Macri Jenna A. , Pressman Eva , Thornburg Loralei L. , Poleshuck Ellen , Bell Keisha , Best Meghan , Barrett Emily , Miller Richard K. , O'Connor Thomas G.
Published: November 2021

Insufficient care in the perinatal period is associated with poorer maternal health, poorer perinatal outcomes, infant mortality, and health inequalities. Identifying the sources of and reducing the rates of insufficient care is therefore a major clinical and public health objective. We propose a specific application of the biopsychosocial model that conceptualizes prenatal and postpartum care quality as health markers that are influenced by psychological factors and family and social context. Clinic attendance data were abstracted from the electronic medical records of N = 291 participants enrolled in a longitudinal pregnancy cohort study of healthy women who have been followed since the first trimester; the Kotelchuck Index (KI) was calculated as an index of perinatal care utilization. Detailed prenatal psychological, social, and sociodemographic data were collected from self-report questionnaire and interview. Bivariate analyses indicated socio-demographic (e.g., race), psychological (e.g., response to perceived racism, affective symptoms, trauma experience), and social and family context (e.g., social support, family size) significantly influenced pre- and post-natal care utilization. Multivariate logistic regression analyses, adjusting for medical complications, identified social and family context as robust predictors of perinatal care utilization. The findings underscore the need for biopsychosocial models of health care and highlight several potential strategies for improving health care utilization.
Association of Neurotensin Receptor 1 Gene Polymorphisms With Defense Mechanisms in Healthy Chinese
Authors: Ma Hui , Li Min , Zhang Liguo , Tao Jiangang , Zhu Gang
Published: November 2021

Aims: In the central nerve system, neurotensin (NT), and neurotensin receptor 1 (NTR1) modulate the dopamine system. Gene variations in the dopamine system have been demonstrated to influence certain defense mechanisms, but no studies have investigated possible effect of NTR1 gene polymorphisms in the biological determination of these defenses. The present study therefore examined this link.

Methods: In 412 healthy Han Chinese, single nucleotide polymorphisms rs6090453C/G, rs6011914C/G, and rs2427422A/G of the NTR1 gene were genotyped, and the defense mechanisms were measured by the self-reporting Defense Style Questionnaire 88.

Results: Significant male-specific differences in the projective identification among the rs6090453 genotypes (p = 0.003); in the intermediate defense, reaction formation, and projective identification among the rs6011914 genotypes (p = 0.011, 0.010, and 0.011, respectively); and in the projective identification among the rs2427422 genotypes (p = 0.005) were found when the level of significance was adjusted by the Bonferroni correction. There was no significant difference in any of the defense scores among genotypes of any single nucleotide polymorphism in the total cohort or female subjects (all p > 0.017). The distributions of genotypes between the low and high score subgroups showed significant differences in the rs2427422 genotype distributions for help-rejecting complaining, regression, and projective identification (p = 0.010, 0.022, and 0.044, respectively). Significant differences were found between males and females in 10 defense mechanisms (all P < 0.05).

Conclusions: The gene variations in the NTR1 polymorphisms were involved in the biological mechanisms of intermediate defense mechanisms, and this effect was influenced by sex.
Wheat Proteins: A Valuable Resources to Improve Nutritional Value of Bread
Authors: Goel Sonia , Singh Mohinder , Grewal Sapna , Razzaq Ali , Wani Shabir Hussain
Published: November 2021

Triticum aestivum, commonly known as bread wheat, is one of the most cultivated crops globally. Due to its increasing demand, wheat is the source of many nutritious products including bread, pasta, and noodles containing different types of seed storage proteins. Wheat seed storage proteins largely control the type and quality of any wheat product. Among various unique wheat products, bread is the most consumed product around the world due to its fast availability as compared to other traditional food commodities. The production of highly nutritious and superior quality bread is always a matter of concern because of its increasing industrial demand. Therefore, new and more advanced technologies are currently being applied to improve and enrich the bread, having increased fortified nutrients, gluten-free, highly stable with enhanced shelf-life, and long-lasting. This review focused on bread proteins with improving wheat qualities and nutritional properties using modern technologies. We also describe the recent innovations in processing technologies to improve various quality traits of wheat bread. We also highlight some modern forms of bread that are utilized in different industries for various purposes and future directions.
Safety and Feasibility of Video-Assisted Thoracoscopic Day Surgery and Inpatient Surgery in Patients With Non-small Cell Lung Cancer: A Single-Center Retrospective Cohort Study
Authors: Dong Yingxian , Shen Cheng , Wang Yan , Zhou Kun , Li Jue , Chang Shuai , Ma Hongsheng , Che Guowei
Published: November 2021

Background and Objective: This study was undertaken to evaluate how safe and viable the use of video-assisted thoracoscopic day surgery (VATDS) is for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC).

Methods: Data obtained from the selected patients with NSCLC who underwent video-assisted thoracoscopic surgery (VATS) in the same medical group were analyzed and a single-center, propensity-matched cohort study was performed. In total, 353 individuals were included after propensity score matching (PSM) with 136 individuals in the day surgery group (DSG) and 217 individuals in the inpatient surgery group (ISG).

Results: The 24-h discharge rate in the DSG was 93.38% (127/136). With respect to the postoperative complications (PPCs), no difference between the two groups was found (DSG vs. ISG: 11.76 vs. 11.52%, p = 0.933). In the DSG, a shorter length of stay (LOS) after surgery (1.47 ± 1.09 vs. 2.72 ± 1.28 days, p < 0.001) and reduced drainage time (8.45 ± 3.35 vs. 24.11 ± 5.23 h, p < 0.001) were found, while the drainage volume per hour (mL/h) was not notably divergent between the relevant groups (p = 0.312). No difference was observed in the cost of equipment and materials between the two groups (p = 0.333). However, the average hospital cost and drug cost of the DSG were significantly lower than those of the ISG (p < 0.001).

Conclusion: The study indicated that the implementation of VATDS showed no difference in PPCs, but resulted in shorter in-hospital stays, shorter drainage times, and lower hospital costs than inpatient surgery. These results indicate the safety and feasibility of VATDS for a group of highly selected patients with early-stage NSCLC.
A Context-Aware Neural Embedding for Function-Level Vulnerability Detection
Authors: Wei Hongwei , Lin Guanjun , Li Lin , Jia Heming
Published: November 2021

Exploitable vulnerabilities in software systems are major security concerns. To date, machine learning (ML) based solutions have been proposed to automate and accelerate the detection of vulnerabilities. Most ML techniques aim to isolate a unit of source code, be it a line or a function, as being vulnerable. We argue that a code segment is vulnerable if it exists in certain semantic contexts, such as the control flow and data flow; therefore, it is important for the detection to be context aware. In this paper, we evaluate the performance of mainstream word embedding techniques in the scenario of software vulnerability detection. Based on the evaluation, we propose a supervised framework leveraging pre-trained context-aware embeddings from language models (ELMo) to capture deep contextual representations, further summarized by a bidirectional long short-term memory (Bi-LSTM) layer for learning long-range code dependency. The framework takes directly a source code function as an input and produces corresponding function embeddings, which can be treated as feature sets for conventional ML classifiers. Experimental results showed that the proposed framework yielded the best performance in its downstream detection tasks. Using the feature representations generated by our framework, random forest and support vector machine outperformed four baseline systems on our data sets, demonstrating that the framework incorporated with ELMo can effectively capture the vulnerable data flow patterns and facilitate the vulnerability detection task.
Associations among Farm, Breed, Lactation Stage and Parity, Gene Polymorphisms and the Fatty Acid Profile of Milk from Holstein, Simmental and Their Crosses
Authors: Samková Eva , Čítek Jindřich , Brzáková Michaela , Hanuš Oto , Večerek Libor , Jozová Eva , Hoštičková Irena , Trávníček Jan , Hasoňová Lucie , Rost Michael , Hálová Karolína , Špička Jiří
Published: November 2021

This study aimed to analyze the factors affecting the fatty acid (FA) profile in cow’s milk. The effects of a farm, lactation parity and stage, breed and polymorphisms in the AGPAT6, DGAT1, LEP, FASN and SCD1 genes were evaluated. A total of 196 Holstein cows, 226 Simmental cows and seven crosses were sampled 751 times. The cows were kept at five farms and were in the first up to the sixth lactation, and 49 individual FAs and 11 groups were analyzed. The farm significantly affected the proportion of all FAs except for C16:1n-7c and isoC14:0. Additionally, the lactation stage was significant for most FAs, and the opposite was true for lactation parity. The effect of the breed was negligible. For the gene polymorphisms, the SCD1 TT genotype exceeded the CC in C10:0, C12:0, C14:0, C16:1n-7c and C18:2, and the opposite was true for C10:1, C12:1, C14:1n-5c, isoC17:0, C16:1 and C18:1, i.e., the TT genotype was higher for saturated FAs, and the CT genotype was higher for monounsaturated FAs. The results hint at the intermediary heredity of the SCD1 gene. The FASN gene was strongly associated with four FAs and branched-chain FAs, and genotype AG was better than GG. LEP was significant for five individual FAs and branched-chain FAs. The differences in FA composition among genotypes were rather small, which could lead to overestimation of the effect and needs to be considered in the next research.