bluuebunny/crossref_metadata_2025 huggingface dataset:
Major disparities in COVID-19 test positivity for patients with non-English preferred language even after accounting for race and social factors in the United States in 2020
Authors: Cohen-Cline Hannah , Li Hsin-Fang , Gill Monique , Rodriguez Fatima , Hernandez-Boussard Tina , Wolberg Harry , Lippa Jacob , Vartanian Keri
Published: November 2021

Background

The COVID-19 pandemic has further exposed inequities in our society, demonstrated by disproportionate COVID-19 infection rate and mortality in communities of color and low-income communities. One key area of inequity that has yet to be explored is disparities based on preferred language.

Methods

We conducted a retrospective cohort study of 164,368 adults tested for COVID-19 in a large healthcare system across Washington, Oregon, and California from March – July 2020. Using electronic health records, we constructed multi-level models that estimated the odds of testing positive for COVID-19 by preferred language, adjusting for age, race/ethnicity, and social factors. We further investigated interaction between preferred language and both race/ethnicity and state. Analysis was performed from October–December 2020.

Results

Those whose preferred language was not English had higher odds of having a COVID-19 positive test (OR 3.07,p < 0.001); this association remained significant after adjusting for age, race/ethnicity, and social factors. We found significant interaction between language and race/ethnicity and language and state, but the odds of COVID-19 test positivity remained greater for those whose preferred language was not English compared to those whose preferred language was English within each race/ethnicity and state.

Conclusions

People whose preferred language is not English are at greater risk of testing positive for COVID-19 regardless of age, race/ethnicity, geography, or social factors – demonstrating a significant inequity. Research demonstrates that our public health and healthcare systems are centered on English speakers, creating structural and systemic barriers to health. Addressing these barriers are long overdue and urgent for COVID-19 prevention.
COVID-19 vaccination acceptance among Syrian population: a nationwide cross-sectional study
Authors: Shibani Mosa , Alzabibi Mhd Amin , Mouhandes Abd El-Fattah , Alsuliman Tamim , Mouki Angie , Ismail Hlma , Alhayk Shahd , Rmman Ahmad Abdulateef , Mansour Marah , Marrawi Marah , Alhalabi Nawras , Habib Mhd Baraa , Albuni Mhd Kutaiba , Al-Moujahed Ahmad , Sawaf Bisher ,   Data Collection Group, Zahrawi Hanaa Wael , Bakdounes Anan Mhd tawfik , Alhouri Ahmad Nabil , Abdulal Nour Zuhir , Hawari Rama Adnan , Safiah Mhd Homam , Alazrak Sara Omar , Husein Rama Ahmad Alsayed , Alshaghel Mohammed Moutaz , Mayo Wafik , Aladna Abdallah , Mwaffak Abdulkader Hajjar , Maarrawi Shahd , Khalil Marah , Almahairi Lana , Mokresh Yaman , Younes Mouhammad Saleh
Published: November 2021

Background

Severe Acute Respiratory Syndrome Coronavirus 2 continues to spread globally and in the absence of an effective treatment, the vaccine remains the best hope for controlling this disease. In this study, we seek to find out the extent to which people in Syria accept the Corona vaccine and what are the factors that affect their decision.

Methods

This cross-sectional study was conducted in Syria during the period from January 3 to March 17, 2021. A structured self-administered questionnaire was distributed in two phases: The first phase included distributing the questionnaire as a Google Form on social media platforms. In the second phase, a paper version of the questionnaire was handed to patients, their companions, and workers in public hospitals. SPSS v.25 and R v.4.1.1 were used to analyze the data. Pearson Chi-square test and Logistic Regression were used to study the associations between categorical groups.

Results

Of 7531 respondents, 3505 (46.5%) were males and 4026 (53.5%) were females. 3124 (41.5%) were 18–24 years old. Healthcare workers were participants’ main sources of information (50.9%), followed by Social Media users (46.3%). 2790 (37%) of the participant are willing to be vaccinated, and 2334 (31%) were uncertain about it. Fear of possible side effects was the main reason for the reluctance to take the vaccine 1615 (62.4%), followed by mistrust of the vaccine formula 1522 (58.8%). 2218 (29.5%) participants think COVID-19 poses a major risk to them personally. Vaccination intention was significantly associated with gender, residence, financial status, educational level, and geographic origin.

Conclusion

This study showed very negatively important results. The study participants Vaccination acceptance rate is almost the lowest when compared to its peers. A Lot of efforts should be made to correct misinformation about the vaccine and answer all questions about it, especially with a health system that has been ravaged by war for 10 years.
Effect of community-based education on undergraduate nursing students’ skills: a systematic review
Authors: Zeydani Arezoo , Atashzadeh-Shoorideh Foroozan , Abdi Fatemeh , Hosseini Meimanat , Zohari-Anboohi Sima , Skerrett Victoria
Published: November 2021

Background

Community-based education, as an effective approach to strengthen nurses’ skills in response to society’s problems and needs has increased in nursing education programs. The aim of this study was to review the effect of community-based education on nursing students’ skills.

Methods

For this systematic review, ProQuest, EMBASE, Scopus, PubMed/ MEDLINE, Cochran Library, Web of Science, CINAHL and Google Scholar were searched up to February 2021. The methodological quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Seventeen studies were included in this systematic review. Inclusion criteria included articles published in English and were original articles.

Results

In all studies, undergraduate nursing students’ skills were improved by participation in a community-based education program. Community-based education enhances professional skills, communication skills, self-confidence, knowledge and awareness, and critical thinking skills and teamwork skills in undergraduate nursing students.

Conclusions

Community-based education should be used as an effective and practical method of training capable nurses to meet the changing needs of society, to improve nurses ‘skills and empower them to address problems in society.
Inferring miRNA-disease associations using collaborative filtering and resource allocation on a tripartite graph
Authors: Nguyen Van Tinh , Le Thi Tu Kien , Nguyen Tran Quoc Vinh , Tran Dang Hung
Published: November 2021

Background

Developing efficient and successful computational methods to infer potential miRNA-disease associations is urgently needed and is attracting many computer scientists in recent years. The reason is that miRNAs are involved in many important biological processes and it is tremendously expensive and time-consuming to do biological experiments to verify miRNA-disease associations.

Methods

In this paper, we proposed a new method to infer miRNA-disease associations using collaborative filtering and resource allocation algorithms on a miRNA-disease-lncRNA tripartite graph. It combined the collaborative filtering algorithm in CFNBC model to solve the problem of imbalanced data and the method for association prediction established multiple types of known associations among multiple objects presented in TPGLDA model.

Results

The experimental results showed that our proposed method achieved a reliable performance with Area Under Roc Curve (AUC) and Area Under Precision-Recall Curve (AUPR) values of 0.9788 and 0.9373, respectively, under fivefold-cross-validation experiments. It outperformed than some other previous methods such as DCSMDA and TPGLDA. Furthermore, it demonstrated the ability to derive new associations between miRNAs and diseases among 8, 19 and 14 new associations out of top 40 predicted associations in case studies of Prostatic Neoplasms, Heart Failure, and Glioma diseases, respectively. All of these new predicted associations have been confirmed by recent literatures. Besides, it could discover new associations for new diseases (or miRNAs) without any known associations as demonstrated in the case study of Open-angle glaucoma disease.

Conclusion

With the reliable performance to infer new associations between miRNAs and diseases as well as to discover new associations for new diseases (or miRNAs) without any known associations, our proposed method can be considered as a powerful tool to infer miRNA-disease associations.
RNA m6A methylation regulators in ovarian cancer
Authors: Guo Jialu , Zheng Jianfeng , Zhang Huizhi , Tong Jinyi
Published: November 2021

N6-methyladenosine (m6A) is the most abundant RNA modification of mammalian mRNAs and plays a vital role in many diseases, especially tumours. In recent years, m6A has become the topic of intense discussion in epigenetics. M6A modification is dynamically regulated by methyltransferases, demethylases and RNA-binding proteins. Ovarian cancer (OC) is a common but highly fatal malignancy in female. Increasing evidence shows that changes in m6A levels and the dysregulation of m6A regulators are associated with the occurrence, development or prognosis of OC. In this review, the latest studies on m6A and its regulators in OC have been summarized, and we focus on the key role of m6A modification in the development and progression of OC. Additionally, we also discuss the potential use of m6A modification and its regulators in the diagnosis and treatment of OC.
Afatinib combined with anlotinib in the treatment of lung adenocarcinoma patient with novel HER2 mutation: a case report and review of the literature
Authors: Xu Huanhuan , Liang Qi , Xu Xian , Tan Shanyue , Wang Sumeng , Liu Yiqian , Liu Lingxiang
Published: November 2021

Background

HER2 is a member of the ERBB family of receptor tyrosine kinases, and HER2 mutations occur in 1–4% of non-small cell lung cancer (NSCLC) as an oncogenic driver mutation. We found a rare mutation of HER2 p.Asp769Tyr in NSCLC.

Case presentation

We presented a case of a 68-year-old nonsmoking male patient with brain metastasis from lung adenocarcinoma harboring a rare mutation of HER2 p.Asp769Tyr. After multiple lines of treatment, he obtained a durable response (10 months) to afatinib and anlotinib.

Conclusion

We reported for the first time that afatinib and anlotinib have successfully treated lung adenocarcinoma with HER2 p.Asp769Tyr mutation. This finding can provide an insight into the optimal treatment of lung adenocarcinoma patients with novel mutations. Additionally, we summarized the efficacy of targeted therapy for HER2 mutant lung cancer in this article.
Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses
Authors: Li Shuang , Wang Xu , Wang Tianfeng , Zhang Huixue , Lu Xiaoyu , Liu Li , Li Lifang , Bo Chunrui , Kong Xiaotong , Xu Si , Ning Shangwei , Wang Jianjian , Wang Lihua
Published: November 2021

Background

Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (MG). The aim of the present study was to explore the roles of lncRNAs as ceRNAs associated with the progression of MG.

Methods

MG risk genes and miRNAs were obtained from public databases. Protein–protein interaction (PPI) network analysis and module analysis were performed. A lncRNA-mediated module-associated ceRNA (LMMAC) network, which integrated risk genes in modules, risk miRNAs and predicted lncRNAs, was constructed to systematically explore the regulatory roles of lncRNAs in MG. Through performing random walk with restart on the network, HCG18/miR-145-5p/CD28 ceRNA axis was found to play important roles in MG, potentially. The expression of HCG18 in MG patients was detected using RT-PCR. The effects of HCG18 knockdown on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interactions among HCG18, miR-145-5p and CD28 were explored by luciferase assay, RT-PCR and western blot assay.

Results

Based on PPI network, we identified 9 modules. Functional enrichment analyses revealed these modules were enriched in immune-related signaling pathways. We then constructed LMMAC network, containing 25 genes, 50 miRNAs, and 64 lncRNAs. Through bioinformatics algorithm, we found lncRNA HCG18 as a ceRNA, might play important roles in MG. Further experiments indicated that HCG18 was overexpressed in MG patients and was a target of miR-145-5p. Functional assays illustrated that HCG18 suppressed Jurkat cell apoptosis and promoted cell proliferation. Mechanistically, knockdown of HCG18 inhibited the CD28 mRNA and protein expression levels in Jurkat cells, while miR-145-5p inhibitor blocked the reduction of CD28 expression induced by HCG18 suppression.

Conclusion

We have reported a novel HCG18/miR-145-5p/CD28 ceRNA axis in MG. Our findings will contribute to a deeper understanding of the molecular mechanism of and provide a novel potential therapeutic target for MG.
Quantification of dendritic cell subsets in human thymus tissues of various ages
Authors: Li Yan , Chen Pei , Huang Hao , Feng Huiyu , Ran Hao , Liu Weibin
Published: November 2021

Background

Dendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also have other functions in the thymus, such as pathogen recognition. The density changes of human thymic DCs have been hardly investigated. In this study, human thymus samples of various ages were collected for tissue sectioning and staining. The thymic cortex and medulla area as well as the densities of various subsets of thymic DCs were calculated.

Results

All common DC subsets were found in the human thymus of various ages. Most DCs had accumulated in the human thymic epithelial space, especially the medulla. We also found that the human thymic cortex had atrophied relatively faster than the medulla, which led to a gradual increase of the area ratio of the medulla to cortex with the increase of age. The densities of DC subsets in the human thymus showed various changes with increasing age, which contributed to the composition changes of DC subsets. The density of plasmacytoid DCs (pDCs) in the human thymus had increased gradually with aging, which suggested that pDCs plays another essential role in the thymus in addition to central tolerance.

Conclusions

Inconsistent with the shrinking of the epithelial space in the thymus, the densities of DC subsets in the epithelial space of the thymus are maintained at a constant level with aging to preserve highly efficient autoreactive thymocyte screening. An increasing density of the thymic pDCs with aging implies an extra function of DCs in the thymus beyond central tolerance.
First dorsal metacarpal artery flap with dorsal digital nerve with or without dorsal branch of the proper digital nerve produces comparable short-term sensory outcomes
Authors: Feng Shi-Ming , Zhao Jia-Ju , Migliorini Filippo , Maffulli Nicola , Xu Wei
Published: November 2021

Background

The first dorsal metacarpal artery flap, including dorsal digital nerves with or without dorsal branches of the proper digital nerves, can be used to reconstruct thumb pulp defects with good results. However, it is still unclear whether there are differences in the sensory outcomes between preserving or not preserving the dorsal branches of the proper digital nerves.

Methods

This retrospective cohort study included 137 thumb pulp defect patients who underwent first dorsal metacarpal artery flap reconstruction procedure from October 2015 to June 2019. Patients were divided into two groups according to whether the dorsal branches of the proper digital nerves were preserved. In the non-preservation group (n = 80), the dorsal digital nerves were included in the flap for sensory reconstruction. In the preservation group (n = 57), the dorsal digital nerves and the dorsal branches of the proper digital nerves of the index finger were included in the flap. The stump of the proper digital nerves in the defect was coaptated to the donor nerves of the flap using the end-to-end fashion. At the last follow-up, static two-point discrimination, Semmes–Weinstein monofilament scores, pain, cold intolerance of the reconstructed finger, and patient satisfaction in both groups were compared.

Results

All patients were followed up for at least 17 months. No significant differences were found regarding pain of thumb pulp, static two-point discrimination, Semmes–Weinstein monofilament score, cold intolerance in the injured finger, and patient satisfaction. The non-preservation group presented slightly shorter operative times (p < 0.05).

Conclusion

There are no differences at 2 years in postoperative clinical outcomes when dorsal digital nerves are used to reconstruct flap sensation regardless of preservation of the dorsal branches of the proper digital nerves in the first dorsal metacarpal artery flap.

Level of evidence: Level III, retrospective comparative study.
International consensus on clinical severity scale use in evaluating Niemann–Pick disease Type C in paediatric and adult patients: results from a Delphi Study
Authors: Evans William , Patterson Marc , Platt Frances , Guldberg Christina , Mathieson Toni , Pacey Jessica ,   the Core Working Group for the Delphi Study, Berry-Kravis Elizabeth , Farhat Nicole , Gascon Jordi , Geberhiwot Tarek , Gissen Paul , Giugliani Roberto , Hastings Caroline , Héron Bénédicte , Imrie Jackie , Jones Simon , Lachmann Robin , Mengel Eugen , Patterson Marc , Pineda Mercedes , Porter Denny , Runz Heiko , Stampfer Miriam , Strupp Michael , Walterfang Mark
Published: November 2021

Background

Several scales have been developed in the past two decades to evaluate Niemann–Pick disease Type C (NPC) severity in clinical practice and trials. However, a lack of clarity concerning which scale to use in each setting is preventing the use of standardised assessments across the world, resulting in incomparable data sets and clinical trial outcome measures. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research.

Methods

A Delphi method of consensus development was used, comprising three survey rounds. In Round 1, participants were asked nine multiple-choice and open-ended questions to gather opinions on the six severity scales and domains. In Rounds 2 and 3, questions aimed to gain consensus on the opinions revealed in Round 1 using a typical Likert scale.

Results

Nineteen experts, active in NPC paediatric and adult research and treatment, participated in this study. Of these, 16/19 completed Rounds 1 and 2 and 19/19 completed Round 3. Consensus (defined as ≥ 70% agreement or neutrality, given the study aim to identify the severity scales that the clinical community would accept for international consistency) was achieved for 66.7% of the multiple-choice questions in Round 2 and 83% of the multiple-choice questions in Round 3. Consensus was almost reached (68%) on the use of the 5-domain NPCCSS scale as the first choice in clinical practice. Consensus was reached (74%) for the 17-domain NPCCSS scale as the first choice in clinical trial settings, but the domains measured in the 5-domain scale should be prioritised as the primary endpoints. Experts called for educational and training materials on how to apply the NPCCSS (17- and 5-domains) for clinicians working in NPC.

Conclusions

In achieving a consensus on the use of the 17-domain NPCCSS scale as the first choice for assessing clinical severity of NPC in clinical trial settings but prioritising the domains in the 5-domain NPCCSS scale for routine clinical practice, this study can help to inform future discussion around the use of the existing NPC clinical severity scales. For routine clinical practice, the study helps provide clarity on which scale is favoured by a significant proportion of a representative body of experts, in this case, the 5-domain NPCCSS scale.
Prenatal diagnosis of a 4.5-Mb deletion at chromosome 4q35.1q35.2: Case report and literature review
Authors: Xiao Gefei , Qiu Xianrong , Zhou Yuqiu , Tan Gongjun , Shen Yao
Published: November 2021

Objective

We present a genetic analysis of an asymptomatic family with a 4q terminal deletion; we also review other similar published studies and discuss the genotype–phenotype correlation.

Methods

A karyotype analysis was performed on the amniotic fluid cells of a woman at 24 weeks of pregnancy and peripheral blood lymphocytes from both parents and their older son with the conventional G-banding technique. Chromosomal microarray analysis (CMA) testing was carried out for both parents and the fetus to analyze copy number variation (CNV) in the whole genome.

Results

The results showed no abnormalities in the karyotypes of the father and older son, and the karyotypes of the mother and fetus were 46,XX,del(4)(q35.1) and 46,XY,del(4)(q35.1), respectively. CMA results showed a partial deletion at the 4q terminus in both the fetus and mother. The deletion region of the fetus was arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) × 1; the loss size of the CNV was approximately 4.5 Mb and involved 14 protein-coding genes, namely, CYP4V2, F11, FAM149A, FAT1, FRG1, FRG2, KLKB1, MTNR1A, PDLIM3, SORBS2, TLR3, TRIML1, TRIML2, and ZFP42. No variation on chromosome 4 was detected in the father’s CMA results.

Conclusion

Deletion of the 4q subtelomeric region is a familial variation. The arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) region single-copy deletion did not cause obvious congenital defects or mental retardation. The application of high-resolution genetic testing technology combined with the analysis of public genetic database information can more clearly elucidate the genotype–phenotype correlation of the disease and provide support for both prenatal and postnatal genetic counseling.
Retraction Note: Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors
Authors: Yuan Jie , Zhang Fan , Hallahan Dennis , Zhang Zhen , He Liming , Wu Ling-Gang , You Meng , Yang Qin
Published: November 2021

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s13046-021-02172-6
Study protocol: evaluation of the addictive potential of e-cigarettes (EVAPE): neurobiological, sociological, and epidemiological perspectives
Authors: Vollstädt-Klein Sabine , Grundinger Nadja , Görig Tatiana , Szafran Daria , Althaus Astrid , Mons Ute , Schneider Sven
Published: November 2021

Background

Tobacco use is the largest preventable cause of diseases and deaths; reducing tobacco intake is, therefore, an urgent public health goal. In recent years, e-cigarettes have been marketed as a 'healthier' alternative to tobacco smoking, whilst product features have evolved tremendously in the meantime. A lively scientific debate has developed regarding the potential benefits and risks of e-cigarettes although, surprisingly, there are few studies investigating the addictive potential of nicotine-containing e-cigarettes. The present work comprises three work packages investigating the addictive potential of e-cigarettes from different perspectives: (1) the neurobiological addictive potential of e-cigarettes; (2) the experience and perception of dependence symptoms among users of e-cigarettes in a social context; and (3) the epidemiological perspective regarding factors influencing the potential for dependence.

Methods

Work package I: the neurobiological study will investigate the key elements of addiction in e-cigarettes compared to tobacco cigarettes using neurobiological and neuropsychological correlates associated with craving, incentive motivation, cue reactivity and attentional bias. Work package II: the sociological study part examines self-reports on the experience and perception of dependence symptoms in a social context, using focus group interviews and the analysis of posts in online discussion forums on e-cigarettes. Work package III: the epidemiological study part focuses on tolerance development and the role of psychosocial and product factors by analyzing longitudinal data from the International Tobacco Control Policy Evaluation Project (ITC).

Discussion

The present study offers a chosen mix of three methodological approaches, thereby comprehensively examining core symptoms of positive and negative reinforcement in addiction. Whether e-cigarettes are as reinforcing and addictive as combustible tobacco cigarettes is an important public health issue with implications for prevention and treatment programs.

Trial registration:Work package I: Registered at clinicaltrials.gov/ct2/show/NCT04772014. Work package II: Registered at OSF Registries:https://osf.io/dxgya(2021, January 14).
Retina tissue validation of optical coherence tomography determined outer nuclear layer loss in FTLD-tau
Authors: Kim Benjamin J. , Lee Vivian , Lee Edward B. , Saludades Adrienne , Trojanowski John Q. , Dunaief Joshua L. , Grossman Murray , Irwin David J.
Published: November 2021

Alzheimer’s disease (AD) is associated with inner retina (nerve fiber and ganglion cell layers) thinning. In contrast, we have seen outer retina thinning driven by photoreceptor outer nuclear layer (ONL) thinning with antemortem optical coherence tomography (OCT) among patients considered to have a frontotemporal degeneration tauopathy (FTLD-Tau). Our objective was to determine if postmortem retinal tissue from FTLD-Tau patients demonstrates ONL loss observed antemortem on OCT. Two probable FTLD-Tau patients that were deeply phenotyped by clinical and genetic testing were imaged with OCT and followed to autopsy. Postmortem brain and retinal tissue were evaluated by a neuropathologist and ocular pathologist, respectively, masked to diagnosis. OCT findings were correlated with retinal histology. The two patients had autopsy-confirmed FTLD-Tau neuropathology and had antemortem OCT measurements showing ONL thinning (66.9 μm, patient #1; 74.9 μm, patient #2) below the 95% confidence interval of normal limits (75.1–120.7 μm) in our healthy control cohort. Postmortem, retinal tissue from both patients demonstrated loss of nuclei in the ONL, matching ONL loss visualized on antemortem OCT. Nuclei counts from each area of ONL loss (2 – 3 nuclei per column) seen in patient eyes were below the 95% confidence interval (4 – 8 nuclei per column for ONL) of 3 normal control retinas analyzed at the same location. Our evaluation of retinal tissue from FTLD-Tau patients confirms ONL loss seen antemortem by OCT. Continued investigation of ONL thinning as a biomarker that may distinguish FTLD-Tau from other dementias is warranted.
IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population
Authors: Sun Yimin , Gao Yong , Zhou Yuxi , Zhou Yulong , Zhang Ying , Wang Dong , Tan Li-Hai
Published: November 2021

Background

Developmental stuttering is the most common form of stuttering without apparent neurogenic or psychogenic impairment. Recently, whole-exome sequencing (WES) has been suggested to be a promising approach to study Mendelian disorders.

Methods

Here, we describe an application of WES to identify a gene potentially responsible for persistent developmental stuttering (PDS) by sequencing DNA samples from 10 independent PDS families and 11 sporadic cases. Sanger sequencing was performed for verification with samples obtained from 73 additional patients with sporadic cases.

Results

We first searched for cosegregating variants/candidate genes in a Chinese family (Family 0) by sequencing DNA obtained from 3 affected members and 3 controls. Next, we sequenced DNA samples obtained from 9 additional Chinese families (Families 1-9) with stuttering to verify the identified candidate genes. Intriguingly, we found that two missense variants (Leu552Pro and Lys428Gln) of interferon-alpha/beta receptor 1 (IFNAR1) cosegregated with stuttering in three independent families (Families 0, 5 and 9). Moreover, we found two additional mutations (Gly301Glu and Pro335del) in the IFNAR1 gene in 4 patients with sporadic cases by using WES or Sanger sequencing. Further receptor mutagenesis and cell signaling studies revealed that these IFNAR1 variants may impair the activity of type I IFN signaling.

Conclusion

Our data indicate that IFNAR1 might be a potential pathogenic gene of PDS in the Chinese population.
Small signal stability enhancement of a large scale power system using a bio-inspired whale optimization algorithm
Authors: Dasu Butti , Mangipudi Sivakumar , Rayapudi Srinivasarao
Published: November 2021

A whale optimization algorithm (WOA)-based power system stabilizer (PSS) design methodology on modified single machine infinite bus (MSMIB) and multi-machine systems to enhance the small-signal stability (SSS) of the power system is presented. The PSS design methodology is implemented using an eigenvalue (EV)-based objective function. The performance of the WOA is tested with several CEC14 and CEC17 test functions to investigate its potential in optimizing the complex mathematical equations. The New England 10-generator 39-bus system and the MSMIB system operating at various loading conditions are considered as the test systems to examine the proposed method. Extensive simulation results are obtained which validate the effectiveness of the proposed WOA method when compared with other algorithms.
Comparison between PI-DTC-SPWM and fuzzy logic for a sensorless asynchronous motor drive
Authors: El Daoudi Soukaina , Lazrak Loubna
Published: November 2021

Currently, asynchronous cage motors are among the most commonly requested machines accentuated by their extension to the field of electric vehicles. Therefore, the development of robust and sophisticated controls for this machine is of significant interest. Artificial intelligence control techniques, such as fuzzy logic, are at the forefront of recent research. However, their design becomes much more complicated for a motor via a multilevel inverter. The main purpose of this paper is to show that it is possible to achieve fuzzy logic control of a squirrel cage asynchronous motor supplied via the usual two-level inverter. This is achieved, by adopting a DTC strategy based on a sinusoidal PWM with multilevel inverter. It employs a feedback information estimator with dual structure between the sliding mode observer at low speed and the model reference adaptive system in sliding mode at high speed. For both installations, speed is regulated using a sliding mode controller.
Morphological and histopathological studies of Thelandros chalcidae (Oxyuroidea: Pharyngodonidae) infecting Chalcides ocellatus from Egypt
Authors: Fol Mona F. , Mostafa Nesma A.
Published: November 2021

Background

Thelandros (Pharyngodonidae) is a gastrointestinal nematode parasite with a life cycle including lizards as main hosts. Thelandros chalcidae collected from the large intestine of the Egyptian ocellated skink, Chalcides ocellatus were described and illustrated by light and scanning electron microscopes. Seven out of fifteen (46.66%) of the examined lizards were found to be naturally infected. Also, host intestinal tissues were evaluated from hematoxylin/eosin-stained sections to describe any histopathological changes.

Results

Microscopic examinations revealed that the recovered pharyngodonid species characterized by mouth with triangular opening and surrounded by six simple lips, the cuticle had regular transverse annulations extending from the posterior margin of the lips to the end of the body. Male was cylindrical with distinct truncated posterior end and measured 1.59–1.86 (1.64 ± 0.10) long and 0.29–0.37 (0.32 ± 0.01) in maximum width at the level of mid-body. Female measured 1.72–2.43 (1.85 ± 0.2) long and 0.36–0.49 (0.42 ± 0.01) maximum width at the mid-body level, terminated posteriorly in a short, stout spike. Histological studies observed structural alterations represented by leukocytic infiltration, villi atrophy, and muscularis degeneration. These changes were indicative of inflammatory and degenerative reaction due to Thelandros chalcidae infection.

Conclusion

The present morphological study revealed that the recovered pharyngodonid species was Thelandros chalcidae causing pathological alterations in Chalcides ocellatus intestinal tissues.
Exploratory and confirmatory molecular approaches to determine genetically modified status in different crops
Authors: Oraby Hanaa Abdel-Sadek , Aboul-Maaty Nadia Aboul-Ftooh , Al-Sharawi Hayam Ahmad
Published: November 2021

Background

One of the parameters required for the assessment of food and feed safety is detection and identification of genetically modified organisms. Legislation in some countries necessitates detection and quantification of modification in food and feed samples. Scientists have raised concern about safety of antibiotic resistance marker (ARM) genes used for transformation of crops intended for human and animal consumption. In the present work two molecular approaches have been adopted: one exploratory; for detection and quantification of ARM genes in tested plant samples and the other confirmatory; to determine the specificity/reliability of the obtained results.

Results

Results revealed that primers for neomycin phosphotransferase (nptII) and aminoglycoside 3″ adenyl-transferase (aadA) were amplified in the majority of the 36 DNA screened samples. Melting curve analysis using hygromycin phosphotransferase (aphIV) gene as target sequence for the fluorescent-based detection approach was performed to ensure reliability and specificity of this procedure and to confirm results obtained by using conventional polymerase chain reaction (PCR). Quantitative RT-PCR results and validation analysis followed, revealed that all of the tested DNA samples were not violating the European legislation for GMOs labeling (0.9%).

Conclusions

The results fully demonstrated the reproducibility, sensitivity/specificity of the adopted approaches for detection and quantification of even traces of GMO contents. Applying measurement uncertainty (MU) procedures presented in this work will help decision makers to ensure compliance with International Legislation and Regulations. This in its turn will facilitate and enhance trading with countries having compelling labeling regulations.
Stigmasterol and β-Sitosterol: Antimicrobial Compounds in the Leaves of Icacina trichantha identified by GC–MS
Authors: Alawode Taye Temitope , Lajide Labunmi , Olaleye Mary , Owolabi Bodunde
Published: November 2021

Background

The development of resistance to many antibiotics currently in use has necessitated the search for more effective alternatives. Plants have been used in ethnomedicine in different parts of the world to treat various diseases. Many studies on plants have confirmed their medicinal potentials and have led to the isolation and characterization of several potential drug candidates. This study investigates the leaves of Icacina trichantha for antimicrobial properties and seeks to identify the compounds responsible for the observed activities. The leaves of Icacina trichantha are used in ethnomedicine for the treatment of skin infections. In this study, a solvent-based fractionation of bioactive compounds in the leaves of Icacina trichantha was carried out using hexane, ethyl acetate, and methanol. The resultant extracts were screened for antimicrobial activity against six bacteria and four fungi using standard procedures. GC–MS analysis of the most active fraction was carried out.

Results

The non-polar fraction (hexane) showed better antimicrobial activity than the ethyl acetate and methanol extracts. At 200 mg/mL, the fraction showed inhibition of 28.0 ± 0.82, 23.7 ± 0.47, and 24.6 ± 0.94 against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis,, respectively. At the same concentration, the extract showed zones of inhibition of 18.0 ± 0.82 against Candida albicans and Penicillium notatum. The lowest Minimum Inhibitory Concentrations (MIC) values of 2.5 mg/mL were obtained against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. GC–MS analysis of the hexane extract revealed 62 peaks, out of which ten peaks were successfully characterized.

Conclusions

None of the extracts screened for antibacterial and antifungal activities in this study is as potent as the standard drugs, Gentamicin and Tioconazole. The hexane extract, however, showed some activity against the microorganisms and was analyzed using GC–MS. The hexane extract contained many bioactive compounds, some of which could not be identified. Two of the identified compounds, Stigmasterol and β-Sitosterol, are known to possess antimicrobial properties. However, the unidentified compounds could also have contributed significantly to the antimicrobial activities of the extract.
Systematic kinetic study of magnesium production using magnesium oxide and carbonic materials at different temperatures
Authors: Zahedi Hamid , Farzi Nahid , Golestani Nasser
Published: November 2021

The main goal of this study was to determine the industrially best reductant for reduction of magnesium oxide to magnesium with wood charcoal and petroleum coke (petcoke) each in molar ratio 1:1 and 1:2 (oxidant:reductant) at high temperatures. In this study, a new and reliable combination of mathematical modeling and discrete numerical optimization theory by presenting 18 “mathematical filters” not relying only on statistical quantities of fitting (contrary to many similar researches) was introduced. The purpose of these filters was the determination of correct kinetic equation and therefore, the corresponding rate coefficient from among 18 equations most used at present in the challenging field of solid state chemical kinetics. With assistance of a new and fundamental mathematical function and the obtained values of rate coefficients, the function of rate coefficient in temperature was attained. The activation energy was then calculated as a function of temperature using the general definition of activation energy and the determined function for rate coefficient. The comparison between different reducing agents in the different conditions and with relevant previous study was accomplished to determine the best reducing agent from industry standpoint. Also, the areas under experimental data were calculated numerically and utilized for method validation and comparison. It turned out finally that relying only on fitting quantities in the solid state chemical kinetics canreadilylead towrongconclusions about the correct kinetic equation and about the most suitable reducing agent. It is obvious that the erroneous calculations and wrong decisions in the laboratory scale become significant and paramount in industry and this reveals the significance of rigorous mathematical analysis.

Graphical abstract
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Authors: Iwama Shintaro , Kobayashi Tomoko , Yasuda Yoshinori , Okuji Takayuki , Ito Masaaki , Ando Masahiko , Zhou Xin , Yamagami Ayana , Onoue Takeshi , Kawaguchi Yohei , Miyata Takashi , Sugiyama Mariko , Takagi Hiroshi , Hagiwara Daisuke , Suga Hidetaka , Banno Ryoichi , Hase Tetsunari , Morise Masahiro , Wakahara Keiko , Yokota Kenji , Kato Masashi , Nishio Naoki , Tanaka Chie , Miyata Kazushi , Ogura Atsushi , Ito Takanori , Sawada Tsunaki , Shimokata Tomoya , Niimi Kaoru , Ohka Fumiharu , Ishigami Masatoshi , Gotoh Momokazu , Hashimoto Naozumi , Saito Ryuta , Kiyoi Hitoshi , Kajiyama Hiroaki , Ando Yuichi , Hibi Hideharu , Sone Michihiko , Akiyama Masashi , Kodera Yasuhiro , Arima Hiroshi
Published: November 2021

Background

Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown.

Methods

A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit.

Results

Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline.

Conclusions

This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.
Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib
Authors: Milioto Angelo , Reyes Monica , Hanna Patrick , Kiuchi Zentaro , Turan Serap , Zeve Daniel , Agarwal Chhavi , Grigelioniene Giedre , Chen Ang , Mericq Veronica , Frangos Myrto , Ten Svetlana , Mantovani Giovanna , Salusky Isidro B , Tebben Peter , Jüppner Harald
Published: November 2021

Context

Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown.

Objective

Determine whether PHP1B encountered after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) causes GNAS remethylation defects similar to those in sporPHP1B.

Design

Retrospective analysis.

Results

Nine among 36 sporPHP1B patients investigated since 2000, all with loss of methylation (LOM) at the 3 maternal GNAS differentially methylated regions (DMRs) and gain of methylation at the paternal NESP DMR, had been conceived through IVF or ICSI. Besides abnormal GNAS methylation, IVF/ICSI PHP1B cases revealed no additional imprinting defects. Three of these PHP1B patients have dizygotic twins, and 4 have IVF/ICSI-conceived siblings, all with normal GNAS methylation; 2 unaffected younger siblings were conceived naturally.

Conclusion

Sporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all 4 GNAS DMRs, thus suggesting a similar underlying disease mechanism. Given that remethylation at the 3 maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM postfertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect or defects in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether the lack of GNAS remethylation alone and the resulting reduction in Gsα expression is sufficient to impair oocyte maturation.
Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function
Authors: Shi Fang-Hong , Li Hao , Shen Long , Xu Li , Ge Heng , Gu Zhi-Chun , Lin Hou-Wen , Pu Jun
Published: November 2021

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients.

Methods

A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included.

Results

Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment.

Conclusions

Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).
The Role of Iodine for Thyroid Function in Lactating Women and Infants
Authors: Andersson Maria , Braegger Christian P
Published: November 2021

Iodine is a micronutrient needed for the production of thyroid hormones, which regulate metabolism, growth, and development. Iodine deficiency or excess may alter the thyroid hormone synthesis. The potential effects on infant development depend on the degree, timing, and duration of exposure. The iodine requirement is particularly high during infancy because of elevated thyroid hormone turnover. Breastfed infants rely on iodine provided by human milk, but the iodine concentration in breast milk is determined by the maternal iodine intake. Diets in many countries cannot provide sufficient iodine, and deficiency is prevented by iodine fortification of salt. However, the coverage of iodized salt varies between countries. Epidemiological data suggest large differences in the iodine intake in lactating women, infants, and toddlers worldwide, ranging from deficient to excessive intake. In this review, we provide an overview of the current knowledge and recent advances in the understanding of iodine nutrition and its association with thyroid function in lactating women, infants, and toddlers. We discuss risk factors for iodine malnutrition and the impact of targeted intervention strategies on these vulnerable population groups. We highlight the importance of appropriate definitions of optimal iodine nutrition and the need for more data assessing the risk of mild iodine deficiency for thyroid disorders during the first 2 years in life.