bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival outcomes in locally advanced dMMR rectal cancer: surgery plus adjunctive treatment vs. surgery alone
Authors: Ni Kemin , Zhan Yixiang , Liu Zhaoce , Yuan Zhen , Wang Shuyuan , Zhao Xuan-zhu , Ping Hangyu , Liu Yaohong , Wang Wanting , Yan Suying , Xin Ran , Han Qiurong , Zhang Qinghuai , Li Guoxun , Zhang Xipeng , Wang Guihua , Zhang Zili , Ma Hong , Zhang Chunze
Published: October 2023

Background

Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone.

Methods

A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan–Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups.

Results

Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263).

Conclusions

For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.
Expression profiles and function prediction of tRNA-derived fragments in glioma
Authors: Wei Deng , Niu Ben , Zhai Bei , Liu Xiao-bai , Yao Yi-long , Liang Chan-chan , Wang Ping
Published: October 2023

Background

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown.

Methods

The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3’UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively.

Results

tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3’UTR.

Conclusion

tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3’UTR.
Prevalence of inherited retinal diseases in a large Egyptian cohort
Authors: Tawfik Caroline Atef , Roshdy Maged Maher , Morris Nancy Magdy
Published: October 2023

Background

Inherited retinal diseases form a rare, highly heterogeneous group of genetic disorders characterized by retinal degeneration. It is considered one of the leading causes of debilitating visual loss and blindness in children and young adults. Despite this few population-based data studies on prevalence of inherited retinal diseases exist. Moreover, prevalence can vary widely depending on geographical area, population ethnicity and cultural habits.

Purpose

To report the prevalence of different subtypes of Inherited retinal diseases in a large Egyptian cohort in a retrospective, hospital-based, cross-sectional study.

Methods

We conducted an extensive electronic medical record search for all the patients attending the outpatient clinic and investigation unit of Ain Shams University Hospital and the two branches of Watany Eye Hospital in the period between January 2015 and October 2022 aiming to identify the prevalence rate of different types of IRDs, patient demographics and stratify them according to their phenotype.

Results

We examined the electronic medical records of 478 222 patients, 971 patients were diagnosed with IRD by clinical examination with or without any of the following investigations: color fundus photography, fundus autofluorescence, fundus fluorescein angiography, optical coherence tomography and/or electrophysiological studies as electroretinogram, visual evoked potential and electrooculogram. The overall prevalence was 0.2%. The most common IRD encountered was isolated retinitis pigmentosa with a percentage of 78.9% followed by Stargardt disease at 6.3%, cone-rod dystrophy at 2.0%, autosomal recessive bestrophinopathy at 1.9% and unspecified IRD at 1.5%.

Conclusion

Retinitis pigmentosa was the most common IRD encountered followed by Stargardt disease. Many of the dystrophies are the subject of clinical intervention trials, and population-based epidemiological data can guide phenotype-based genetic testing and help assess the future need for treatment.
A qualitative analysis of stress experiences and coping strategies in adolescents with Crohn's disease
Authors: Zhou Xiao-juan , Huang Shuai
Published: October 2023

Background

In this study, we investigated the coping mechanisms and stress perceptions of adolescent patients with Crohn's disease.

Methods

Using semi-structured face-to-face interviews, we conducted an extensive qualitative study of the disease perceptions, stress experiences, and corresponding coping mechanisms in adolescent patients with Crohn's disease. We used Colaizzi content analysis to synthesize the themes.

Results

The two main themes in this study were inappropriate coping mechanisms and physical and psychological stress. The primary initiators of physical and psychological stress in adolescents with Crohn's disease were weak disease perception, symptom distress, negative emotions, lack of support, and multiple stressors. The decrease in self-management and self-control induced by the initiators led to changes in cognition, emotions, and attitudes, which subsequently led to poor coping behavior.

Conclusion

Adolescents with Crohn's disease can better combat the condition by implementing appropriate coping strategies. Their mental health should be given attention, and a multidisciplinary team should be assembled to provide them with supportive care.
A nested case-control study of the effects of dust exposure, smoking on COPD in coal workers
Authors: Wang Hui , Meng Rui , Wang Xuelin , Si Zhikang , Zhao Zekun , Lu Haipeng , Wang Huan , Hu Jiaqi , Zheng Yizhan , Chen Jiaqi , Zhao Ziqi , Zhu Hongmin , Li Xiaoming , Xue Ling , Yan Shengguang , Sun Jian , Su Yu , Wu Jianhui
Published: October 2023

Background

Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction.

Method

A nested case–control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017–2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers.

Results

The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers.

Conclusion

Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.
Mexican Americans agree to participate in longitudinal clinical research more than non-Hispanic whites
Authors: Chen Chen , Shi Xu , Lisabeth Lynda D , Kwicklis Madeline , Malvitz Madelyn , Case Erin , Morgenstern Lewis B
Published: October 2023

Background

The National Institutes of Health has advocated for improved minority participation in clinical research, including clinical trials and observational epidemiologic studies since 1993. An understanding of Mexican Americans (MAs) participation in clinical research is important for tailoring recruitment strategies and enrollment techniques for MAs. However, contemporary data on MA participation in observational clinical stroke studies are rare. We examined differences between Mexican Americans (MAs) and non-Hispanic whites (NHWs) participation in a population-based stroke study.

Methods

We included 3,594 first ever stroke patients (57.7% MAs, 48.7% women, median [IQR] age 68 [58–79]) from the Brain Attack Surveillance in Corpus Christi Project, 2009–2020 in Texas, USA, who were approached and invited to participate in a structured baseline interview. We defined participation as completing a baseline interview by patient or proxy. We used log-binomial models adjusting for prespecified potential confounders to estimate prevalence ratios (PR) of participation comparing MAs with NHWs. We tested interactions of ethnicity with age or sex to examine potential effect modification in the ethnic differences in participation. We also included an interaction between year and ethnicity to examine ethnic-specific temporal trends in participation.

Results

Baseline participation was 77.0% in MAs and 64.2% in NHWs (Prevalence Ratio [PR] 1.20; 95% CI, 1.14–1.25). The ethnic difference remained after multivariable adjustment (1.17; 1.12–1.23), with no evidence of significant effect modification by age or sex (Pinteraction by age = 0.68, Pinteraction by sex = 0.83). Participation increased over time for both ethnic groups (Ptrend < 0.0001), but the differences in participation between MAs and NHWs remained significantly different throughout the 11-year time period.

Conclusion

MAs were persistently more likely to participate in a population-based stroke study in a predominantly MA community despite limited outreach efforts towards MAs during study enrollment. This finding holds hope for future research studies to be inclusive of the MA population.
Development and evaluation of the Rural and Northern Community Focused Model of COPD Care (RaNCoM)
Authors: Freeman Shannon , Peach Laura , Ross Christopher , Marchal Kathy , Meyer Anthon , Skinner Kelly
Published: October 2023

Background

The prevalence of COPD continues to rise. To address the challenges to provide high quality COPD care in rural and northern communities, leaders in one rural and northern community in Western Canada sought to change the culture of COPD screening and care. Recognizing effective assessment, diagnosis, and treatment for patients with COPD are crucial to improve outcomes, a program was developed between 2012 and 2021 to enhance primary care for COPD patients.

Methods

A process evaluation was undertaken to assess program development, implementation, mechanisms of impact, and context of COPD program. Qualitative thematic analysis of stakeholder interviews (n = 11) and a document review (n = 60; ~ 500 pages) of key clinic documents was conducted.

Results

We describe five phases of the COPD program’s development (Survive; Reorganize and Stabilize; Assess and Respond; Build and Refine; and Sustain and Share), highlighting areas of innovation. Outreach and localizing resources improved access to the program. Acquiring secured physician compensation, capturing quality data, and improving patient and provider self-efficacy built the capacity of the system and stakeholders within it. Finally, relationships were forged through building an integrated facility, collaborative networking, and patient engagement. Key elements of program implementation included the resources (infrastructure, software, operational) required to ensure operation.

Conclusion

Team-based care and service integration enhanced care capacity and the health network. Focused use of infrastructure and resources supported the people in the care system. Upholding a shared value of relationship is critical to deliver robust and sustainable rural healthcare. Quality improvement requires investment in rural community healthcare resources.
Atypical diabetes with spontaneous remission associated with systemic lupus erythematosus in an adolescent girl of African ancestry, a case report
Authors: Luterbacher Fanny , Blouin Jean-Louis , Schwitzgebel Valerie M.
Published: October 2023

Background

New-onset diabetes in youth encompasses type 1 diabetes, type 2 diabetes, monogenic diabetes, and rarer subtypes like Type B insulin resistance syndrome and ketosis-prone atypical diabetes in African populations. Some cases defy classification, posing management challenges. Here, we present a case of a unique, reversible diabetes subtype.

Case presentation

We describe an adolescent African girl recently diagnosed with systemic lupus erythematosus. At age 15, she presented with ketoacidosis, HbA1c of 108.7 mmol/mol (12.1%), and positive anti-insulin antibodies. Initially diagnosed with type 1 diabetes, insulin was prescribed. Due to the presence of obesity and signs of insulin resistance, we added metformin. Concurrently, she received treatment for lupus with hydroxychloroquine, mycophenolate mofetil, and prednisone. After discharge, she stopped insulin due to cultural beliefs. Five months later, her glycemia and HbA1c normalized (37 mmol/mol or 5.5%) without insulin, despite corticosteroid therapy and weight gain. Autoantibodies normalized, and lupus activity decreased. Genetic testing for monogenic diabetes was negative, and the type 1 genetic risk score was exceptionally low.

Conclusions

We present a complex, reversible diabetes subtype. Features suggest an autoimmune origin, possibly influenced by overlapping HLA risk haplotypes with lupus. Lupus treatment or immunomodulation may have impacted diabetes remission. Ancestry-tailored genetic risk scores are currently designed to improve diagnostic accuracy.
Effect of application of short-form video health education on the health knowledge and satisfaction with nursing care of patients with lower extremity fractures
Authors: Zheng Yuliu , Yan Qiuyan
Published: October 2023

Background

Video health education has been increasingly adopted in the clinic to expand patient guidance and improve perioperative outcomes. To date, however, it is unclear whether the use of short-form videos and web-based clinician-created forums actually improve the perioperative experience of patients.

Objective

To evaluate the effect of application of short-form video health education on the health knowledge and satisfaction with nursing care of patients with lower extremity fractures.

Methods

This study is a quasi experimental study, using convenient sampling method and grouping according to historical control., one hundred and twenty-two patients admitted with lower limb fractures to the orthopedic ward of a tertiary first-class general hospital in Fujian, China were enrolled in this study. Based on their admission order, patients admitted from September 2021 to November 2021 were enrolled into the control group (n = 61) and patients admitted from December 2021 to March 2022 were enrolled in the intervention group (n = 61). Both groups received identical admission-based patient education, perioperative care, and discharge rehabilitation instructions. The control group received the traditional education method while the intervention group received a short-form educational video in addition to the traditional education method. Patient perioperative health knowledge and patient satisfaction with nursing care during treatment of lower limb fractures were compared across the two groups.

Results

Preoperative health knowledge in the intervention group was 95.1%, compared to 82.0% in the control group (χ2 = 3.954, P<0.05). The Newcastle satisfaction with nursing scales score in the intervention group was (80.902 ± 7.016) points, compared to (78.131 ± 8.213) points in the control group. These group differences were statistically significant (P < 0.05).

Conclusion

The application of a short-form educational video during the perioperative care of patients with lower limb fractures may improve patients’ understanding of perioperative health and increase satisfaction with nursing care.
Site assessment survey to assess the impact of the COVID-19 pandemic on HIV clinic site services and strategies for mitigation in Washington, DC
Authors: Barish Nicole , Barth Shannon , Monroe Anne K. , Greenberg Alan E. , Castel Amanda D. ,   DC Cohort Executive Committee, Rakhmanina Natella , Barnes Clover , Serlin Michael , Kumar Princy , Temprosa Marinella , Bhandaru Vinay , Bezabeh Tsedenia , Grover Nisha , Mele Lisa , Reamer Susan , Sapozhnikova Alla , Strylewicz Greg , Xiao Jiayang , Byrne Morgan , Hammerlund Shannon , Kulie Paige , Peterson James , Stewart Bianca , Ma Yan , Lucar Jose , Gajjala Jhansi L. , Rana Sohail , Horberg Michael , Fernandez Ricardo , Taylor Duane , Bordon Jose , Teferi Gebeyehu , Benator Debra , Denyer Rachel , Ruiz Maria Elena , Abbott Stephen
Published: October 2023

Introduction

The COVID-19 pandemic has created substantial interruptions in healthcare presenting challenges for people with chronic illnesses to access care and treatment services. We aimed to assess the impact of the pandemic on HIV care delivery by characterizing the pandemic-related impact on HIV clinic-level services and the mitigation strategies that were developed to address them.

Methods

The data comes from a site assessment survey conducted in the DC Cohort, an observational clinical cohort of PWH receiving care at 14 HIV outpatient clinics in Washington, D.C. Frequency counts and prevalence estimates of clinic-level survey responses about the impact of care delivery, COVID-19 testing, and vaccinations and mitigation strategies are presented.

Results

Clinics reported an increase in temporary clinic closures (n = 2), reduction in clinic hours (n = 5), telehealth utilization (n = 10), adoption of multi-month dispensation of antiretroviral (ARV) medication (n = 11) and alternative drug delivery via postal/courier service, home/community delivery or pick-up (n = 11). Clinics utilized strategies for PWH who were lost to follow-up during the pandemic including offering care to persons with any income level and insurance status (n = 9), utilizing e-prescribing for auto refills even if the patient missed visits (n = 8), and utilization of the regional health information exchange to check for hospitalizations of PWH lost to follow-up (n = 8). Most social services offered before the pandemic remained available during the pandemic; however, some support services were modified.

Conclusions

Our findings demonstrate the extent of pandemic-era disruptions and the use of clinic-level mitigation strategies among urban HIV clinics. These results may help prepare for future pandemic or public health emergencies that disrupt healthcare delivery and access.
Single-cell Mayo Map (scMayoMap): an easy-to-use tool for cell type annotation in single-cell RNA-sequencing data analysis
Authors: Yang Lu , Ng Yan Er , Sun Haipeng , Li Ying , Chini Lucas C. S. , LeBrasseur Nathan K. , Chen Jun , Zhang Xu
Published: October 2023

Background

Single-cell RNA-sequencing (scRNA-seq) has become a widely used tool for both basic and translational biomedical research. In scRNA-seq data analysis, cell type annotation is an essential but challenging step. In the past few years, several annotation tools have been developed. These methods require either labeled training/reference datasets, which are not always available, or a list of predefined cell subset markers, which are subject to biases. Thus, a user-friendly and precise annotation tool is still critically needed.

Results

We curated a comprehensive cell marker database named scMayoMapDatabase and developed a companion R package scMayoMap, an easy-to-use single-cell annotation tool, to provide fast and accurate cell type annotation. The effectiveness of scMayoMap was demonstrated in 48 independent scRNA-seq datasets across different platforms and tissues. Additionally, the scMayoMapDatabase can be integrated with other tools and further improve their performance.

Conclusions

scMayoMap and scMayoMapDatabase will help investigators to define the cell types in their scRNA-seq data in a streamlined and user-friendly way.
Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339
Authors: Wang Miaomiao , Wang Yang , Yang Liu , Du Xing , Li Qifa
Published: October 2023

Background

Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus.

Results

We identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis.

Conclusions

Our findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.
A large pedigree study confirmed the CGG repeat expansion of RILPL1 Is associated with oculopharyngodistal myopathy
Authors: Yang Xinzhuang , Zhang Dingding , Shen Si , Li Pidong , Li Mengjie , Niu Jingwen , Ma Dongrui , Xu Dan , Li Shuangjie , Guo Xueyu , Wang Zhen , Zhao Yanhuan , Ren Haitao , Ling Chao , Wang Yang , Fan Yu , Shen Jianxiong , Zhu Yicheng , Wang Depeng , Cui Liying , Chen Lin , Shi Changhe , Dai Yi
Published: October 2023

Background

Oculopharyngodistal myopathy (OPDM) is an autosomal dominant adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1, NOTCH2NLC and RILPL1 were reported to be the etiologies for OPDM.

Results

In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 21 patients diagnosed with typical OPDM. We identified CGG repeat expansions in 5’UTR of RILPL1 gene in all patients we tested while no CGG expansion in unaffected family members. Repeat-primed PCR and fluorescence amplicon length analysis PCR were further confirmed the segregation of CGG expansions in other family members and 1000 normal Chinese controls. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was consistent with previous studies. Our findings provide evidence that RILPL1 is associated OPDM in this large pedigree.

Conclusions

Our results identified RILPL1 is the associated the disease in this large pedigree.
The provision of malaria services in border districts of four countries in Southern Africa: results from a cross-sectional community assessment of malaria border health posts
Authors: Chisenga Mukosha , Dlamini Bongani , Mwendera Nyasha , Maquina Paulo , Hamainza Busiku , Martins José Franco , Saute Francisco , Bock Henrico , Gosling Roly , Bennett Adam , Smith Jennifer , Kleinschmidt Immo
Published: October 2023

Background

The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas.

Methods

Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel.

Results

Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria.

Conclusions

The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.
Robust preimplantation genetic testing of the common F8 Inv22 pathogenic variant of severe hemophilia A using a highly polymorphic multi-marker panel encompassing the paracentric inversion
Authors: Nguyen Minh Tam , Nguyen Thanh Tung , Nguyen Duy Bac , Nguyen Thi Mai , Nguyen Kim Ngan , Ngo Van Nhat Minh , Nguyen Van Dieu , Tran Ngoc Anh , Lian Mulias , Tan Arnold S. C. , Chong Samuel S. , Dang Tien Truong
Published: October 2023

Background

Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging.

Methods

Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity.

Results

All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term.

Conclusion

Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers.
A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials
Authors: Kelly Sharmony B. , Tran Nhi T. , Polglase Graeme R. , Hunt Rodney W. , Nold Marcel F. , Nold-Petry Claudia A. , Olson David M. , Chemtob Sylvain , Lodygensky Gregory A. , Robertson Sarah A. , Gunn Alistair J. , Galinsky Robert
Published: October 2023

Background

Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential.

Methods

We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690).

Results

Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias.

Conclusion

Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation.
Measuring cell-to-cell expression variability in single-cell RNA-sequencing data: a comparative analysis and applications to B cell aging
Authors: Zheng Huiwen , Vijg Jan , Fard Atefeh Taherian , Mar Jessica Cara
Published: October 2023

Background

Single-cell RNA-sequencing (scRNA-seq) technologies enable the capture of gene expression heterogeneity and consequently facilitate the study of cell-to-cell variability at the cell type level. Although different methods have been proposed to quantify cell-to-cell variability, it is unclear what the optimal statistical approach is, especially in light of challenging data structures that are unique to scRNA-seq data like zero inflation.

Results

We systematically evaluate the performance of 14 different variability metrics that are commonly applied to transcriptomic data for measuring cell-to-cell variability. Leveraging simulations and real datasets, we benchmark the metric performance based on data-specific features, sparsity and sequencing platform, biological properties, and the ability to recapitulate true levels of biological variability based on known gene sets. Next, we use scran, the metric with the strongest all-round performance, to investigate changes in cell-to-cell variability that occur during B cell differentiation and the aging processes. The analysis of primary cell types from hematopoietic stem cells (HSCs) and B lymphopoiesis reveals unique gene signatures with consistent patterns of variable and stable expression profiles during B cell differentiation which highlights the significance of these methods. Identifying differentially variable genes between young and old cells elucidates the regulatory changes that may be overlooked by solely focusing on mean expression changes and we investigate this in the context of regulatory networks.

Conclusions

We highlight the importance of capturing cell-to-cell gene expression variability in a complex biological process like differentiation and aging and emphasize the value of these findings at the level of individual cell types.
SPIRAL: integrating and aligning spatially resolved transcriptomics data across different experiments, conditions, and technologies
Authors: Guo Tiantian , Yuan Zhiyuan , Pan Yan , Wang Jiakang , Chen Fengling , Zhang Michael Q. , Li Xiangyu
Published: October 2023

Properly integrating spatially resolved transcriptomics (SRT) generated from different batches into a unified gene-spatial coordinate system could enable the construction of a comprehensive spatial transcriptome atlas. Here, we propose SPIRAL, consisting of two consecutive modules: SPIRAL-integration, with graph domain adaptation-based data integration, and SPIRAL-alignment, with cluster-aware optimal transport-based coordination alignment. We verify SPIRAL with both synthetic and real SRT datasets. By encoding spatial correlations to gene expressions, SPIRAL-integration surpasses state-of-the-art methods in both batch effect removal and joint spatial domain identification. By aligning spots cluster-wise, SPIRAL-alignment achieves more accurate coordinate alignments than existing methods.
Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity
Authors: Ruyssen-Witrand Adeline , Guernec Gregory , Dupont Julia , Lapuyade Diane , Lioté Frédéric , Vittecoq Olivier , Degboé Yannick , Constantin Arnaud
Published: October 2023

Background

To compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).

Methods

We included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years.

Results

Patients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups.

Conclusion

RA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.
Misdiagnosed metabolic bone abnormality: a case report
Authors: Alsabri Mohammed , Street Hannah , Sircy Aaron , Labib Bahaaeldin
Published: October 2023

Background

Metabolic bone disease causes significant morbidity and mortality, especially when misdiagnosed. With genetic testing, multiple disease pathologies can be analyzed.

Case presentation

A 5-year and 9-month-old otherwise healthy Yemeni girl presented to her Yemen physician for evaluation of inward bending of her right knee and short stature. After extensive medical testing, she was given a diagnosis of hypophosphatemic rickets and growth hormone deficiency and started on treatment. Despite appropriate treatment, however, her condition continued to progress, prompting her family to pursue additional workup including genetic testing outside of Yemen. Genetic testing ultimately revealed a variation of unknown significance associated with amelogenesis imperfecta.

Conclusions

Hypophosphatemic rickets secondary to renal tubular acidosis was the working diagnosis. However, the patient’s condition did not improve. Further genetic testing revealed a variation of unknown significance associated with amelogenesis imperfecta. We aim to present this case, provide an overview of the causes, and diagnostic metabolic bone health evaluation.
Treatment of severe metformin-associated lactic acidosis with renal replacement therapy and tris-hydroxymethyl aminomethane: a case report
Authors: Yusim Diana , Tiru Bogdan , Abdullin Marat , Landry Daniel L. , Hodgins Spencer , Braden Gregory L.
Published: October 2023

Background

Type B lactic acidosis is a rare but serious side effect of metformin use. The risk of metformin-associated lactic acidosis is elevated in renal or liver impairment, heart failure and in metformin overdose. Metformin-associated lactic acidosis is treated with renal replacement therapy although this can be limited by metformin’s large volume of distribution and a patient’s hemodynamic instability. Tris-hydroxymethyl aminomethane is a buffer that rapidly equilibrates in liver cells and increases the intracellular pH of hepatocytes. Intracellular alkalosis increases lactate uptake by the liver and can promote gluconeogenesis which results in increased lactate metabolism and decreased lactate production. Unlike intravenous bicarbonate which can worsen acidosis due to carbon dioxide retention and hypocalcemia, tris-hydroxymethyl aminomethane does not generate large amounts of carbon dioxide and can improve cardiac contractility in experimental models.

Case presentation

We present a case of a 43-year-old African American male who intentionally ingested 480,000 g of metformin. He developed severe metformin-associated lactic acidosis that was refractory to 21 hours of high flux hemodialysis. This was followed by an additional 12 hours of high flux hemodialysis augmented by continuous intravenous infusion of tris-hydroxymethyl aminomethane. After initiating tris-hydroxymethyl aminomethane, the patient had rapid reversal of lactic acidosis and was weaned off vasopressors and mechanical ventilation.

Conclusions

While metformin-associated lactic acidosis can be treated with renal replacement therapy, severe cases of lactic acidosis may not be amenable to renal replacement therapy alone. Through its unique buffer mechanisms, tris-hydroxymethyl aminomethane can be used in conjunction with dialysis to rapidly improve acidosis associated with metformin.
Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: a systematic review and meta-analysis
Authors: Lu Wenming , Qu Jiayang , Yan Longxiang , Tang Xingkun , Wang Xuesong , Ye Anqi , Zou Zhengwei , Li Lincai , Ye Junsong , Zhou Lin
Published: October 2023

Aim

Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis.

Method

The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4.

Results

A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects.

Conclusion

The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.
The historical evolution of the Greek retail trade: a first overview of its organisational-functional and spatial restructuring
Authors: Manioudis Manolis , Meramveliotakis Giorgos
Published: October 2023

The history of retailing has become an area of growing scholarly interest over the last few decades, with publications mainly concerning the national historiography of retail and wholesaling. On the other hand, although the retail sector is considered to be one of the most historically significant sectors of the Greek economy, the economic history of the Greek retail industry remains a notoriously underdeveloped area of inquiry and, as such, is on the margins of economic and social studies in Greek historiography. In this paper, we, attempt to provide a first concise (and certainly not exhaustive) analysis of the historical development of the Greek retail sector from the nineteenth century to the present (in circa) day. Specifically, we aim to analyse the evolution of the Greek retail trade to assess the spatial and social impacts associated with establishing and operating “new forms” of commerce. The focus is on the sectoral and organisational restructuring of the retail trade with the changes in the standards of the spatial location, which relate to the establishment and operation of retail businesses. Students and scholars of the history of retailing would benefit from this worthwhile exercise which for the first time provides a first overview of the historical development of the Greek retail sector.
The relationship between positive and negative stress and posttraumatic growth in university students: the mediating role of resilience
Authors: Serpa-Barrientos Antonio , Calvet María Luisa Matalinares , Acosta Ana Gloria Díaz , Fernández Ana Cecilia Pareja , Rivas Díaz Luisa Hortensia , Albites Flor María Ayala , Saintila Jacksaint
Published: October 2023

Background

Information on understanding the mediating role of resilience in the relationship between posttraumatic growth (PTG) and positive and negative stress among students is limited. The objective of this research was to evaluate the mediating role of resilience in the relationship between positive and negative stress and PTG in university students.

Methods

The research was carried out using an associative strategy with an empirical approach and explanatory design, with a sample of 507 participants whose average age was 22.38 years ($${\text{S}\text{D}}_{\text{a}\text{g}\text{e}}$$= 3.758), the sample was mostly composed of women (70.4%).

Results

The results allow us to describe that resilience plays a complete mediating role in the relationship between negative stress and PTG. On the other hand, mediation was partial when resilience mediated the relationship between positive stress and PTG. In addition, multigroup invariance analyses according to gender and geographic context show that there is no difference in males, females, and the region where they reside.

Conclusion

In conclusion, the hypothesis that resilience fulfills the mediating function is ratified.