bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis
Authors: Fan Kai , Zhou Shican , Jin Ling , Tan Shiwang , Lai Ju , Zhang Zimu , Li Jingwen , Xu Xiayue , Yao Chunyan , Yan Zhiqiang , Yu Shaoqing
Published: July 2023

Background

Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR.

Methods

The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment.

Results

GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1.

Conclusion

Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.
Fear of falling as a mediator in the association between social frailty and health-related quality of life in community-dwelling older adults
Authors: Wu Kuan-Ying , Chen Duan-Rung , Chan Chang-Chuan , Yeh Yen-Po , Chen Hsiu-Hsi
Published: July 2023

Background

Social frailty is associated with Fear of Falling (FoF) and health-related quality of life (HrQoL). However, how social frailty simultaneously influences FoF and HrQoL remains unclear. The study aims to understand the links between social frailty, FoF, and HrQoL in older adults and the mediating role of FoF in the relations between social frailty and HrQoL.

Methods

In this cross-sectional survey, 1,933 community-dwelling older adults from Changhua County, Taiwan, were interviewed using a self-administrated questionnaire. In total, 1,251 participants with complete data were included for analysis. Data were analyzed using the SPSS PROCESS macro. A simple mediation was employed using social frailty as the independent variable, FoF as the mediator variable, and HrQoL as the outcome variable.

Results

Social frailty was associated with HrQoL and indirectly with HrQoL through FoF, and FoF was directly associated with HrQoL. Of the 5-item social frailty index, “going out less frequently” was correlated with HrQoL and indirectly with HrQoL through FoF. Individuals who felt unhelpful toward family or friends had the worst physical HrQoL and did not talk to someone daily had the most negative influence on mental HrQoL.

Conclusions

Social frailty can directly and indirectly, through FoF decrease HrQoL. It also emphasizes the importance of social connectivity in reducing the risk of falls. This study points to the need for social connectivity and fall prevention programs as essential components of strategies to enhance the health and well-being of community-dwelling older adults.
Clinical significance of B7-H3 expression in circulating CD4+CD25high T cells, CD14+ monocytes, and plasma for the progression of HIV infection
Authors: Xu Jun-Chi , Chen Hui , Xu Ping , You Xin-Ran , Zhu Geng-chao , Gao Fei
Published: July 2023

Background

B7-H3 is an important immune checkpoint molecule that plays a negative role in immune regulation. This study was aimed to explore B7-H3 expression in HIV-infected patients and its clinical significance.

Methods

To explore the expression and clinical significance of B7-H3 in HIV-infected patients, we investigated the B7-H3 expression pattern and the correlation of B7-H3 expression with clinical parameters of HIV-infected patients with different levels of CD4+ T cells. To assess the role of B7-H3 in regulating the function of T cells in HIV infection, we performed a proliferation assay and T cell function test in vitro.

Results

B7-H3 expression in HIV-infected patients was significantly higher than that in healthy controls. mB7-H3 expression on CD4+CD25high T cells and CD14+ monocytes increased with disease progression. mB7-H3 expression on CD4+CD25high T cells and monocytes was negatively correlated with lymphocyte count, CD4+T cell count, and positively correlated with HIV viral load in HIV-infected patients. when the number of CD4+ T cells in HIV-infected patients was ≥ 200/µL, sB7-H3 and mB7-H3 expression levels on CD4+CD25high T cells and monocytes were negatively correlated with lymphocyte count, CD4+T cell count. sB7-H3 and mB7-H3 expression on monocytes were positively correlated with HIV viral load. B7-H3 inhibited the proliferation of lymphocytes and the secretion of IFN-γ in vitro, especially the ability of CD8+ T cells to secrete IFN-γ.

Conclusions

B7-H3 played an important negative regulatory role in anti-HIV infection immunity. It could be used as a potential biomarker for the progression of HIV infection and a novel target for the treatment of HIV infection.
Use of period analysis to provide a timely assessment of 5-year relative survival for pancreatic cancer patients from Taizhou, eastern China
Authors: Lu Ye , He Min , Lian Liyou , Lei Huijun , Cheng Yongran , Wang Liangyou , Chen Tianhui , Chen Jinfei
Published: July 2023

Assessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014–2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients (< 55, 55–64, 65–74, and > 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004–2008, 2009–2013, and 2014–2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.
The association between physical activity and subjective well-being among adolescents in southwest China by parental absence: a moderated mediation model
Authors: Zhang Ming , Xu Xiaohe , Jiang Jianjun , Ji Yuanyi , Yang Ruixi , Liu Qijiao , Li Shiying , Li Yuchen , Liu Qiaolan
Published: July 2023

Objectives

Built on the Positive Youth Development (PYD) framework, this study examined how physical activity affected the subjective well-being of adolescents in the multi-ethnic area of southwest China. The mediating role of school connectedness as an external development asset and the moderating role of resilience as an internal development asset were specified and tested within the framework of sport-based PYD.

Methods

A cross-sectional survey of 3143 adolescents (47.2% boys with mean age = 12.88 and SD = 1.68) was conducted in 2020. A structural equation model (SEM) was developed to estimate the direct effect of physical activity, the mediating effect of school connectedness, and the moderating effect of resilience on adolescents’ subjective well-being. Multi-group comparison was made to investigate differences and similarities across three parental absence subgroups: (1) both parents present, (2) one parent absent, and (3) both parents absent.

Results

As surmised, physical activity, school connectedness, and resilience all positively and significantly affected adolescents’ subjective well-being. SEM analyses revealed that school connectedness mediated the effect of physical activity on subjective well-being. Moreover, resilience moderated both the direct and indirect effects of physical activity (through school connectedness) on subjective well-being. Finally, the multi-group comparison revealed a moderating effect of parental absence on the moderated mediation model.

Limitations

This study is a cross-sectional survey, so inference of causal associations among the study variables is impossible.

Conclusions

Healthy lifestyle behaviors, school-supportive settings, and positive individual development assets can enhance the subjective well-being of adolescents in southwest China, especially those whose parents were absent. Physical activity interventions informed by the PYD framework should be incorporated into public health programs designed to foster the physical and mental health of left-behind adolescents in southwest China.
Ventilator management and risk of air leak syndrome in patients with SARS-CoV-2 pneumonia: a single-center, retrospective, observational study
Authors: Miyake Nodoka , Igarashi Yutaka , Nakae Ryuta , Mizobuchi Taiki , Masuno Tomohiko , Yokobori Shoji
Published: July 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is reportedly associated with air leak syndrome (ALS), including mediastinal emphysema and pneumothorax, and has a high mortality rate. In this study, we compared values obtained every minute from ventilators to clarify the relationship between ventilator management and risk of developing ALS.

Methods

This single-center, retrospective, observational study was conducted at a tertiary care hospital in Tokyo, Japan, over a 21-month period. Information on patient background, ventilator data, and outcomes was collected from adult patients with SARS-CoV-2 pneumonia on ventilator management. Patients who developed ALS within 30 days of ventilator management initiation (ALS group) were compared with those who did not (non-ALS group).

Results

Of the 105 patients, 14 (13%) developed ALS. The median positive-end expiratory pressure (PEEP) difference was 0.20 cmH2O (95% confidence interval [CI], 0.20–0.20) and it was higher in the ALS group than in the non-ALS group (9.6 [7.8–20.2] vs. 9.3 [7.3–10.2], respectively). For peak pressure, the median difference was -0.30 cmH2O (95% CI, -0.30 – -0.20) (20.4 [17.0–24.4] in the ALS group vs. 20.9 [16.7–24.6] in the non-ALS group). The mean pressure difference of 0.0 cmH2O (95% CI, 0.0–0.0) (12.7 [10.9–14.6] vs. 13.0 [10.3–15.0], respectively) was also higher in the non-ALS group than in the ALS group. The difference in single ventilation volume per ideal body weight was 0.71 mL/kg (95% CI, 0.70–0.72) (8.17 [6.79–9.54] vs. 7.43 [6.03–8.81], respectively), and the difference in dynamic lung compliance was 8.27 mL/cmH2O (95% CI, 12.76–21.95) (43.8 [28.2–68.8] vs. 35.7 [26.5–41.5], respectively); both were higher in the ALS group than in the non-ALS group.

Conclusions

There was no association between higher ventilator pressures and the development of ALS. The ALS group had higher dynamic lung compliance and tidal volumes than the non-ALS group, which may indicate a pulmonary contribution to ALS. Ventilator management that limits tidal volume may prevent ALS development.
Associations of health literacy, personality traits, and pro-individualism with the willingness to complete advance directives in Taiwan
Authors: Chen Duan-Rung , Weng Hui-Ching
Published: July 2023

Background

Studies indicated that patients with advance directives (ADs) have a generally better quality of life near death. Yet, the concept of ADs is relatively new in East Asian countries. This study examined the associations between health literacy, pro-individualism in end-of-life (EOL) decisions (i.e., EOL pro-individualism), and master-persistence personality traits with the willingness to complete ADs.

Methods

The data is from a representative data of 1478 respondents from the 2022 Taiwan Social Change Survey. Generalized structural equation modeling (GSEM) was used to conduct path analysis.

Results

Nearly half of the respondents (48.7%) were willing to complete ADs. Health literacy has direct and indirect effects through EOL pro-individualism values on the willingness to complete ADs. Noncognitive factors such as mastery-persistence personality traits and EOL pro-individualism values enhanced the willingness to complete ADs.

Conclusion

A personalized communication strategy, mindful of personality dimensions and cultural values, can address individual fears and concerns, promoting the benefits of advance care planning (ACP). These influences can provide a roadmap for healthcare providers to customize their approach to ACP discussions, improving patient engagement in AD completion.
The dual role dilemma of liver transplantation health care professionals
Authors: Binder Annette , Fenchel Julia , Lang Immanuel , Batra Anil
Published: July 2023

Background

Similar to many other countries, in Germany patients with alcohol-related liver disease are obliged to prove their abstinence before being accepted on a waitlist for liver transplantation. Health care professionals (HCPs) must both treat patients and ensure that patients have proven their abstinence. The aim of this exploratory study was to develop a deeper understanding of how HCPs deal with this dual role.

Methods

The study used semi-structured interviews as the source of data. 11 healthcare professionals from ten of the 22 German transplant centers were interviewed. After transcription, a qualitative content analysis was performed.

Results

We found that these HCPs faced an ethical dilemma, as they must balance the roles of being both a treatment provider (the therapist role) and an assessor (the monitoring role). To solve this dilemma, the strategy seems to be a tendency for the HCPs to take on one dominant role amongst these two roles. HCPs who prefer to take on the therapist role seem to feel burdened by the 6-month abstinence rule and the obligation to monitor their patients. HCPs who prefer to take on the monitoring role tend to have negative assumptions about the patients. HCPs also reported the impression that patients perceive HCPs as more involved in monitoring and less open to the therapeutic role. From this it can be deduced that current regulations and structures lead both to stress for HCPs and to suboptimal therapy for those affected.

Conclusions

The results showed that current transplantation guidelines can have a negative impact on both patient care and the burdens on the HCPs. From our point of view, there are various changes that could be made to the current clinical practice that would help solve this dilemma. For instance, integrating other assessment criteria that are more closely adapted to the health status trajectory and psychosocial background of the individual patient would be both possible and would lead to improvements in practice.
Institutional review boards in Saudi Arabia: the first survey-based report on their functions and operations
Authors: AlFattani Areej , AlBedah Norah , AlShahrani Asma , Alkawi Ammar , AlMeharish Amani , Altwaijri Yasmin , Omar Abeer , AlKawi M. Zuheir , Khogeer Asim
Published: July 2023

Background

Institutional review boards (IRBs) are formally designated to review, approve, and monitor biomedical research. They are responsible for ensuring that researchers comply with the ethical guidelines concerning human research participants. Given that IRBs might face different obstacles that cause delays in their processes or conflicts with investigators, this study aims to report the functions, roles, resources, and review process of IRBs in Saudi Arabia.

Method

This was a cross-sectional self-reported survey conducted from March 2021 to March 2022. The survey was sent to 53 IRB chairpersons and the administration directors (or secretary) across the country through email after receiving verbal consent. The validated survey consisted of eight aspects: (a) organizational aspects, (b) membership and educational training, (c) submission arrangements and materials, (d) minutes, (e) review procedures, (f) communicating a decision, (g) continuing review, and (h) research ethics committee (REC) resources. A total of 200 points indicated optimal IRB functions.

Results

Twenty-six IRBs across Saudi Arabia responded to the survey. Overall, the IRBs in this study scored a total of 150/200 of the points on the self-assessment tool. Relatively newer IRBs (established less than ten years ago) conducted meetings at least once in a month, had annual funding, had more balanced gender representation, tended to score higher than older IRBs. The organizational aspect score was the lowest among all items in the survey (14.3 score difference, p-value < 0.01). The average turnaround time for expedited research from proposal submission to final decision was 7 days, while it was 20.5 days for the full committee review.

Conclusion

Saudi IRBs performed generally well. However, there is room for focused improvement with respect to extra resources and organizational issues that require closer evaluation and guidance from the regulatory bodies.
Liver in infections: a single-cell and spatial transcriptomics perspective
Authors: Zou Ju , Li Jie , Zhong Xiao , Tang Daolin , Fan Xuegong , Chen Ruochan
Published: July 2023

The liver is an immune organ that plays a vital role in the detection, capture, and clearance of pathogens and foreign antigens that invade the human body. During acute and chronic infections, the liver transforms from a tolerant to an active immune state. The defence mechanism of the liver mainly depends on a complicated network of intrahepatic and translocated immune cells and non-immune cells. Therefore, a comprehensive liver cell atlas in both healthy and diseased states is needed for new therapeutic target development and disease intervention improvement. With the development of high-throughput single-cell technology, we can now decipher heterogeneity, differentiation, and intercellular communication at the single-cell level in sophisticated organs and complicated diseases. In this concise review, we aimed to summarise the advancement of emerging high-throughput single-cell technologies and re-define our understanding of liver function towards infections, including hepatitis B virus, hepatitis C virus, Plasmodium, schistosomiasis, endotoxemia, and corona virus disease 2019 (COVID-19). We also unravel previously unknown pathogenic pathways and disease mechanisms for the development of new therapeutic targets. As high-throughput single-cell technologies mature, their integration into spatial transcriptomics, multiomics, and clinical data analysis will aid in patient stratification and in developing effective treatment plans for patients with or without liver injury due to infectious diseases.
Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes
Authors: Shumba Patience , Sura Thomas , Moll Kirsten , Chakrakodi Bhavya , Tölken Lea A. , Hoßmann Jörn , Hoff Katharina J. , Hyldegaard Ole , Nekludov Michael , Svensson Mattias , Arnell Per , Skrede Steinar ,   INFECT Study Group, Hedetoft Morten , Bruun Trond , Oppegaard Oddvar , Nedrebø Torbjørn , Rath Eivind , Madsen Martin Bruun , Norrby-Teglund Anna , Siemens Nikolai
Published: July 2023

Background

Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase.

Methods

Bacterial infiltration, immune cell influx, tissue necrosis and inflammation in patient´s biopsies were determined using immunohistochemistry. SpeB secretion and activity by GAS post infections or challenges with reactive agents were determined via Western blot or casein agar and proteolytic activity assays, respectively. Proteome of GAS single colonies and neutrophil secretome were profiled, using mass spectrometry.

Results

Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation.

Conclusions

Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.
First validation study of the living with long term conditions scale (LwLTCs) among English-speaking population living with Parkinson’s disease
Authors: Ambrosio Leire , Hislop-Lennie Kelly , Serrano-Fuentes Nestor , Driessens Corine , Portillo Mari Carmen
Published: July 2023

Introduction

Parkinson’s disease is the second most prevalent neurodegenerative disease, affecting 10 million people worldwide. Health and social care professionals need to have personalised tools to evaluate the process of living with Parkinson’s disease and consequently, plan individualised and targeted interventions. Recently, the English version of the Living with Long term conditions (LwLTCs) scale has been developed filling an important gap related to person-centred tools to evaluate the process of living with long term conditions among English-speaking population. However, no validation studies for testing its psychometric properties have been conducted.

Aim

To analyse the psychometric properties of the LwLTCs scale in a wide English-speaking population living with Parkinson’s disease.

Methods

Validation study, with an observational and cross-sectional design. The sample was composed of individuals living with Parkinson’s disease from non-NHS services in the community. Psychometric properties including feasibility and acceptability, internal consistency, reproducibility, and construct, internal and known-groups validity were tested.

Results

A total sample of 241 people living with Parkinson’s disease were included. 6 individuals did not complete 1 or 2 items on the scale. Ordinal alpha was 0.89 for the total scale. The intraclass correlation coefficient for the total scale was 0.88. The LwLTCs scale is strongly correlated with scales measuring satisfaction with life (rs=0.67), quality of life (rs=0.54), and moderately correlated with social support (rs=0.45). Statistically significant difference just for therapy and co-morbidity, yet no for gender, employment situation, or lifestyle changes.

Conclusions

The LwLTCs scale is a valid scale to evaluate how the person is living with Parkinson’s disease. Future validation studies to prove the repeatability of the total scale and particularly, domains 3-Self-management, and 4-Integration and internal consistency will be needed. Developing further studies on the English version of the LwLTC in people with other long term conditions is also proposed.
Ten-year follow-up study of a young woman with loeys-dietz syndrome: a case report
Authors: Nakajima Tomohiro , Iba Yutaka , Shibata Tsuyoshi , Hosaka Itaru , Nakazawa Jyunji , Kawaharada Nobuyoshi
Published: July 2023

We herein report the 10-year surgical course of a 27-year-old woman who underwent two surgeries after being diagnosed with Loeys-Dietz syndrome. As described in previous cases, this patient developed ectopic arterial enlargement. We followed her temporal changes over a 10-year period, including the changes in computed tomography, pathology, and surgery.
Did angiodysplasia associated with heyde’s syndrome disappear spontaneously?: a case report
Authors: Li Rui , Ji Shuliang , Shi Jiaxi , Qing Lijin , Wu Wei , Zhang Jiechun
Published: July 2023

Background

Heyde’s syndrome can be easily overlooked or misjudged in clinical practice because it shares common clinical manifestations with multiple diseases as well as limited accuracy of several corresponding examinations for diagnosing Heyde’s triad. Moreover, aortic valve replacement is often delayed in these patients due to the contradiction between anticoagulation and hemostasis. Herein, we present a rare case of atypical Heyde’s syndrome. The patient’s severe intermittent gastrointestinal bleeding was not completely cured even through a local enterectomy. In the absence of direct evidence of acquired von Willebrand syndrome (AVWS) or angiodysplasia, her long-standing gastrointestinal bleeding was finally stopped after receiving transcatheter aortic valve implantation (TAVI).

Case presentation

A 64-year-old female suffered from refractory gastrointestinal bleeding and exertional dyspnoea. A local enterectomy was performed owing to persistent hemorrhage and repeated transfusions; subsequently, histological examination revealed angiodysplasia. Heyde’s syndrome was not suspected until 3 years later, at which time the patient started bleeding again and was also found to have severe aortic valve stenosis upon echocardiography. TAVI was consequently performed when the patient was in a relatively stable condition even though the predisposition to bleed, but there was no evidence of angiodysplasia and AVWS during angiography at that time. The patient’s above symptoms were significantly relieved after TAVI and followed up for 2 years without any significant ischemic or bleeding events.

Conclusions

The visible characteristics of angiodysplasia or a shortage of HMWM-vWFs should not be indispensable for the clinical diagnosis of Heyde’s syndrome. Enterectomy could be a bridging therapy for aortic valve replacement in patients with severe hemorrhage, and TAVI may be beneficial for moderate to high surgical-risk patients even if they have a potential risk of bleeding.
17q25.3 copy number changes: association with neurodevelopmental disorders and cardiac malformation
Authors: Sahajpal Nikhil Shri , Jeffrey David H. F. , DuPont Barbara R. , Hilton Benjamin
Published: July 2023

Copy number variants (CNVs) have been identified as common genomic variants that play a significant role in inter-individual variability. Conversely, rare recurrent CNVs have been found to be causal for many disorders with well-established genotype–phenotype relationships. However, the phenotypic implications of rare non-recurrent CNVs remain poorly understood. Herein, we re-investigated 18,542 cases reported from chromosomal microarray at Greenwood Genetic Center from 2010 to 2022 and identified 15 cases with CNVs involving the 17q25.3 region. We report the detailed clinical features of these subjects, and compare with the cases reported in the literature to determine genotype–phenotype correlations for a subset of genes in this region. The CNVs in the 17q25.3 region were found to be rare events, with a prevalence of 0.08% (15/18542) observed in our cohort. The CNVs were dispersed across the entire 17q25.3 region with variable breakpoints and no smallest region of overlap. The subjects presented with a wide range of clinical features, with neurodevelopmental disorders (autism spectrum disorder, intellectual disability, developmental delay) being the most common features (80%), then expressive language disorder (33%), and finally cardiovascular malformations (26%). The association of CNVs involving the critical gene-rich region of 17q25.3 with neurodevelopmental disorders and cardiac malformation, implicates several genes as plausible drivers for these events.
DNA double-strand break genetic variants in patients with premature ovarian insufficiency
Authors: Ding Xuechun , Gong Xiaowei , Fan Yingying , Cao Jinghe , Zhao Jingyu , Zhang Yixin , Wang Xiaomei , Meng Kai
Published: July 2023

Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.
The effectiveness of non-surgical interventions in athletes with groin pain: a systematic review and meta-analysis
Authors: Lahuerta-Martín Silvia , Robles-Pérez Román , Hernando-Garijo Ignacio , Jiménez-del-Barrio Sandra , Hernández-Lázaro Héctor , Mingo-Gómez María Teresa , Ceballos-Laita Luis
Published: July 2023

Background

Groin pain is a common pathology among athletes, presenting pain and a reduced range of motion (ROM) as clinical characteristics. Passive physical therapy (PPT) and exercise therapy (ET) interventions are chosen firstly before surgery. The aim of this systematic review and meta-analysis was: (i) to qualitative review the effects of each non-surgical intervention; (ii) to quantitative compare the effects of PPTs plus ET intervention to ET in isolation in pain intensity, and hip ROM in athletes with groin pain.

Methods

A systematic review and meta-analysis was conducted. Pubmed, PEDro, Web of science, Scopus and Cochrane library were searched. Randomized controlled trials comparing PPT plus ET to ET interventions were included. The methodological quality and risk of bias of the included studies, were assessed with the PEDro scale and the Cochrane risk-of-bias tool. To assess the certainty of evidence the GRADEpro GDT was used. Meta-analyses were conducted using RevMan 5.4 using mean difference analysis to assess the variables pain intensity and hip ROM.

Results

A total of 175 studies was identified from the consulted databases. Five studies were included for systematic- review, from which three studies were meta-analyzed. The methodological quality of the included studies ranged from poor to high. ET compared to PPT plus ET provided statistically significant improvements in pain intensity in the short-term (MD = 2.45; 95% CI 1.11, 3.79; I2:65%). No statistically significant differences between interventions were obtained for hip ROM in the short-term.

Conclusions

The qualitative review showed that PPTs plus ET and ET seem to have positive effects on pain intensity and hip ROM. The quantitative analysis found very low certainty of evidence proposing a positive effect in pain intensity for ET interventions based on hip muscles stretching, compared to PPT combined with ET, in the short-term.
Process, structural, and outcome quality indicators to support perioperative opioid stewardship: a rapid review
Authors: Thomas C. , Ayres M. , Pye K. , Yassin D. , Howell S. J. , Alderson S.
Published: July 2023

Opioids are effective analgesics but can cause harm. Opioid stewardship is key to ensuring that opioids are used effectively and safely. There is no agreed set of quality indicators relating to the use of opioids perioperatively. This work is part of the Yorkshire Cancer Research Bowel Cancer Quality Improvement programme and aims to develop useful quality indicators for the improvement of care and patient outcomes at all stages of the perioperative journey.

A rapid review was performed to identify original research and reviews in which quality indicators for perioperative opioid use are described. A data tool was developed to enable reliable and reproducible extraction of opioid quality indicators.

A review of 628 abstracts and 118 full-text publications was undertaken. Opioid quality indicators were identified from 47 full-text publications. In total, 128 structure, process and outcome quality indicators were extracted. Duplicates were merged, with the final extraction of 24 discrete indicators. These indicators are based on five topics: patient education, clinician education, pre-operative optimization, procedure, and patient-specific prescribing and de-prescribing and opioid-related adverse drug events.

The quality indicators are presented as a toolkit to contribute to practical opioid stewardship. Process indicators were most commonly identified and contribute most to quality improvement. Fewer quality indicators relating to intraoperative and immediate recovery stages of the patient journey were identified. An expert clinician panel will be convened to agree which of the quality indicators identified will be most valuable in our region for the management of patients undergoing surgery for bowel cancer.
Psychometric properties of an Arabic translation of the Inflexible Eating Questionnaire (IEQ) in a non-clinical sample of adults
Authors: Fekih-Romdhane Feten , Azzi Vanessa , Malaeb Diana , Sarray El Dine Abir , Obeid Sahar , Hallit Souheil
Published: July 2023

Background

The Inflexible Eating Questionnaire (IEQ) is an 11-item instrument designed to evaluate the behavioural and psychological components of inflexible eating. However, the psychometric properties of the instrument have been infrequently examined, and no previous work has examined its utility in the context of the Middle East.

Methods

A total of 826 Lebanese citizens and residents completed a novel Arabic translation of the IEQ, as well as previously validated measures of body appreciation, functionality appreciation, and disordered eating.

Results

The unidimensional factor structure of the IEQ was upheld through both exploratory and confirmatory factor analyses, with all 11 items retained. We obtained evidence of scalar invariance across gender and found that there were no significant differences in observed IEQ scores between men and women. IEQ scores were also found to have adequate composite reliability and adequate patterns of concurrent validity.

Conclusion

The present findings provide support for the psychometric properties of the Arabic version of the IEQ in examining inflexible eating in Arabic-speaking adults in Lebanon.

Plain English Summary

Inflexible or rigid dietary restraint reflects an all-or-none approach that encompasses feeling compelled to obey a set of self-imposed dieting rules (e.g., avoiding high-calorie food, calorie counting, fasting to lose weight and/or skipping meals), having a sense of self-control and feeling empowered when adhering to these rules, and not respecting or following internal/external cues of hunger, satiety, and appetite. Therefore, the inflexible eating construct is composed of two dimensions, the first one is behavioural (i.e., obeying restrictive dietary rules) and the second one is psychological (i.e., the belief that following these rules is a consistent must). Until recently, the measures designed to assess inflexible eating focused on the behavioral dimension, while omitting to account for the psychological processes underlying the construct. To bridge this gap, the Inflexible Eating Questionnaire (IEQ), an 11-item self-report measure, was developed to assess both the behavioural and psychological components of dietary restraint. To date, the IEQ is not yet validated in Arabic. Through the present study, we aimed to examine the psychometric properties of an Arabic translation of the IEQ, which would in turn facilitate improved research and clinical practices related to dietary restraint in Arabic-speaking nations. Overall, findings provided support for the good psychometric qualities of the Arabic version of the IEQ, which suggests its utility for detecting inflexible eating in Arabic-speaking adults.
Single retinal image for diabetic retinopathy screening: performance of a handheld device with embedded artificial intelligence
Authors: Penha Fernando Marcondes , Priotto Bruna Milene , Hennig Francini , Przysiezny Bernardo , Wiethorn Bruno Antunes , Orsi Julia , Nagel Isabelle Beatriz Freccia , Wiggers Brenda , Stuchi Jose Augusto , Lencione Diego , de Souza Prado Paulo Victor , Yamanaka Fernando , Lojudice Fernando , Malerbi Fernando Korn
Published: July 2023

Background

Diabetic retinopathy (DR) is a leading cause of blindness. Our objective was to evaluate the performance of an artificial intelligence (AI) system integrated into a handheld smartphone-based retinal camera for DR screening using a single retinal image per eye.

Methods

Images were obtained from individuals with diabetes during a mass screening program for DR in Blumenau, Southern Brazil, conducted by trained operators. Automatic analysis was conducted using an AI system (EyerMaps™, Phelcom Technologies LLC, Boston, USA) with one macula-centered, 45-degree field of view retinal image per eye. The results were compared to the assessment by a retinal specialist, considered as the ground truth, using two images per eye. Patients with ungradable images were excluded from the analysis.

Results

A total of 686 individuals (average age 59.2 ± 13.3 years, 56.7% women, diabetes duration 12.1 ± 9.4 years) were included in the analysis. The rates of insulin use, daily glycemic monitoring, and systemic hypertension treatment were 68.4%, 70.2%, and 70.2%, respectively. Although 97.3% of patients were aware of the risk of blindness associated with diabetes, more than half of them underwent their first retinal examination during the event. The majority (82.5%) relied exclusively on the public health system. Approximately 43.4% of individuals were either illiterate or had not completed elementary school. DR classification based on the ground truth was as follows: absent or nonproliferative mild DR 86.9%, more than mild (mtm) DR 13.1%. The AI system achieved sensitivity, specificity, positive predictive value, and negative predictive value percentages (95% CI) for mtmDR as follows: 93.6% (87.8–97.2), 71.7% (67.8–75.4), 42.7% (39.3–46.2), and 98.0% (96.2–98.9), respectively. The area under the ROC curve was 86.4%.

Conclusion

The portable retinal camera combined with AI demonstrated high sensitivity for DR screening using only one image per eye, offering a simpler protocol compared to the traditional approach of two images per eye. Simplifying the DR screening process could enhance adherence rates and overall program coverage.
Battery energy storage-based system damping controller for alleviating sub-synchronous oscillations in a DFIG-based wind power plant
Authors: Verma Neevatika , Kumar Narendra , Kumar Rajeev
Published: July 2023

This paper presents the issue of the Sub-synchronous resonance (SSR) phenomenon in a series compensated DFIG-based wind power plant and its alleviation using a Battery Energy Storage-based Damping Controller (BESSDCL). A supplementary damping signal is developed considering the angular speed deviation and is incorporated into the BESS control system. Wide-area Measurement System data is used to determine the angular speed deviation. A linearized system model is developed to perform eigenvalue analysis, and to detect and examine unstable SSR modes. The variation of wind speed and three-phase fault are also taken into consideration to validate the robustness of the controller. To further verify the efficacy of the proposed damping controller, time-domain simulations are performed using MATLAB/Simulink. The application of the proposed BESSDCL stabilizes all the unstable system modes effectively at wind speeds of 7 m/s, 9 m/s, and 11 m/s, and at 40%, 50%, and 60% series compensation levels, as well three-phase fault conditions.
The Severity of Chronic Cough Diary (SCCD): development and content validation of a novel patient-reported outcome instrument for evaluating the symptom experience of chronic cough
Authors: de la Orden Abad Margarita , Haberland Claudia , Karn Hayley , Skalicky Anne , Hareendran Asha
Published: July 2023

Background

Refractory chronic cough (RCC), a cough lasting longer than 8 weeks with an unexplained underlying etiology and unresponsive to conventional treatment, can have substantial effects on patients’ quality of life. For assessment of the efficacy of antitussive medication in clinical trials in RCC, patient-reported outcome (PRO) instruments should be fit for purpose with appropriate content validity. Here we describe the qualitative testing of a newly developed PRO instrument: the Severity of Chronic Cough Diary (SCCD).

Methods

The SCCD was developed to assess patients’ symptom experience of cough in patients with RCC. A preliminary version was tested and refined based on an iterative process in a qualitative study. In total, three rounds of interviews were conducted with adult participants diagnosed with RCC in the USA (n = 19) and UK (n = 10). Rounds 1–3 consisted of hybrid concept elicitation (CE) interviews and cognitive interviews (CIs), with Round 3 also including interviews in a subset of participants (n = 5) about the usability of the SCCD as administered on an electronic handheld device.

Results

The CE interviews identified concepts important to patients’ experiences related to RCC that were broadly in line with the concepts in the preliminary version of the SCCD. Participants provided positive feedback on the draft SCCD across all CI rounds, reporting the instrument to be relevant and straightforward to complete, and containing a comprehensive set of concepts to evaluate their symptom experience of RCC. Participants demonstrated a good understanding of proposed item wording, response options, and the 24-hour recall period, and thought completion of the SCCD on the electronic device was easy. Following revisions based on results from each interview round, the SCCD at the end of this qualitative research study had 14 items assessing the concepts of: cough symptoms (five items), symptoms related to cough (four items), disruption to activities due to cough (three items), and disruption to sleep due to cough (two items).

Conclusions

The results of this study provide qualitative evidence supporting the content validity of the SCCD as a PRO instrument for evaluating outcomes of therapies for RCC in clinical trials.
Balancing co-benefits and trade-offs between climate change mitigation and adaptation innovations under mixed crop-livestock systems in semi-arid Zimbabwe
Authors: Homann-Kee Tui Sabine , Valdivia Roberto O. , Descheemaeker Katrien , Sisito Gevious , Moyo Elisha N. , Mapanda Farai
Published: July 2023

Achieving Zimbabwe’s national and international commitments to food systems transformation and climate resilience building is of high priority. Integrated simulation-based research approaches developed under the Agricultural Model Intercomparison and Improvement Project (AgMIP) are important sources of evidence to guide policy decisions towards sustainable intensification. Through the identification of economically viable, socially inclusive and environmentally sustainable development pathways, the analysis in this study evaluates co-benefits and trade-offs between climate change adaptation and mitigation interventions for vulnerable smallholder crop-livestock holdings in the semi-arid regions of Zimbabwe. We explore how climate effects disrupt the livelihoods and food security for diverse farm types, the extremely vulnerable and those better resource endowed but facing high risks. In an iterative process with experts and stakeholders, we co-developed context specific development pathways. They include market-oriented adaptation and mitigation interventions and social protection mechanisms that would support the transition towards more sustainable intensified, diversified and better integrated crop-livestock systems. We assess the trade-offs associated with adoption of climate-smart interventions aimed at improving incomes and food security but that may have consequences on GHG emissions for the different pathways and farm types. The approach and results inform the discussion on drivers that can bring about sustainable intensification, and the extent to which socio-economic benefits could enhance the uptake of emission reducing technologies thereof. Through this strategy we evaluate interventions that can result in win–win outcomes, that is, adaptation-mitigation co-benefits, and what this would imply for policies that aim at transforming agri-food systems.