bluuebunny/crossref_metadata_2025 huggingface dataset:
An intersectional analysis of long COVID prevalence
Authors: Cohen Jennifer , van der Meulen Rodgers Yana
Published: December 2023

Background

Long COVID symptoms – which include brain fog, depression, and fatigue – are mild at best and debilitating at worst. Some U.S. health surveys have found that women, lower income individuals, and those with less education are overrepresented among adults with long COVID, but these studies do not address intersectionality. To fill this gap, we conduct an intersectional analysis of the prevalence and outcomes of long COVID in the U.S. We posit that disparities in long COVID have less to do with the virus itself and more to do with social determinants of health, especially those associated with occupational segregation and the gendered division of household work.

Methods

We use 10 rounds of Household Pulse Survey (HPS) data collected between June 2022 and March 2023 to perform an intersectional analysis using a battery of descriptive statistics that evaluate (1) the prevalence of long COVID and (2) the interference of long COVID symptoms with day-to-day activities. We also use the HPS data to estimate a set of multivariate logistic regressions that relate the odds of having long COVID and activity limitations due to long COVID to a set of individual characteristics as well as intersections by sex, race/ethnicity, education, and sexual orientation and gender identity.

Results

Findings indicate that women, some people of color, sexual and gender minorities, and people without college degrees are more likely to have long COVID and to have activity limitations from long COVID. Women have considerably higher odds of developing long COVID compared to men, a disparity exacerbated by having less education. Intersectional analysis by gender, race, ethnicity, and education reveals a striking step-like pattern: college-educated men have the lowest prevalence of long COVID while women without college educations have the highest prevalence. Daily activity limitations are more evenly distributed across demographics, but a different step-like pattern is present: fewer women with degrees have activity limitations while limitations are more widespread among men without degrees. Regression results confirm the negative association of long COVID with being a woman, less educated, Hispanic, and a sexual and gender minority, while results for the intersectional effects are more nuanced.

Conclusions

Results point to systematic disparities in health, highlighting the urgent need for policies that increase access to quality healthcare, strengthen the social safety net, and reduce economic precarity.
A novel “prime and pull” strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge
Authors: Wang Zhannan , He Yingkai , Wang Wenfeng , Tian Yawen , Ge Chongbo , Jia Futing , Zhang Tongyu , Zhang Gerui , Wang Mingyue , Gong Jinshuo , Huang Haibin , Wang Jianzhong , Shi Chunwei , Yang Wentao , Cao Xin , Zeng Yan , Wang Nan , Qian Aidong , Jiang Yanlong , Yang Guilian , Wang Chunfeng
Published: December 2023

Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel “prime and pull” strategy for addressing the production of protective TRM cells in vaccine design.
Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective
Authors: Nayab Dur E , Din Fakhar ud , Ali Hussain , Kausar Warda Arooj , Urooj Shaiza , Zafar Maryam , Khan Ibrahim , Shabbir Kanwal , Khan Gul Majid
Published: December 2023

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease’s origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Graphical abstract
Multiple venous thromboembolisms in a pregnant patient carrying a novel mutation in SERPINC1 (p.M313T) that causes a transient antithrombin deficiency: a case report
Authors: Huang Yuwen , Wang Yinling , Wang Xiaoli , Liu Jue , Luo Bing , Gao Yuanmei
Published: December 2023

Background

Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene (SERPINC1). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms.

Case presentation

We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced.

Conclusions

Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.
Professional care workforce: a rapid review of evidence supporting methods of recruitment, retention, safety, and education
Authors: Morris Meg E. , Brusco Natasha K. , McAleer Rachael , Billett Stephen , Brophy Lisa , Bryant Rosemary , Carey Leeanne , Wright Amy Conley , East Christine , Eckert Marion , Edvardsson Kristina , Fetherstonhaugh Deirdre , Fowler-Davis Sally , Frederico Margarita , Gray Richard , McCaskie Doug , McKinstry Carol , Mitchell Rebecca , Oldenburg Brian , Shields Nora , Smith Karen , Spelten Evelien , Taylor Nicholas , Thwaites Claire , Young Suzanne , Blackberry Irene
Published: December 2023

Background

Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce.

Methods

A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality.

Results

5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary.

Conclusions

Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention.

Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721
The art of equity: critical health humanities in practice
Authors: Mathieu Irène P. , Martin Benjamin J.
Published: December 2023

Background

The American Association of Medical Colleges has called for incorporation of the health humanities into medical education, and many medical schools now offer formal programs or content in this field. However, there is growing recognition among educators that we must expand beyond empathy and wellness and apply the health humanities to questions of social justice – that is, critical health humanities. In this paper we demonstrate how this burgeoning field offers us tools for integrating social justice into medical education, utilizing the frameworks of critical consciousness and structural competency.

Practice of health humanities

Critical health humanities can be applied at multiple levels of learners, and in a variety of contexts. We are two physician-writers who have developed several educational programs that demonstrate this. We taught a seminar that introduced first-year and second-year undergraduates to concepts such as social determinants of health, intergenerational trauma, intersectionality, resilience, and cross-cultural care through works of fiction, poetry, film, podcasts, stand-up comedy, and more. Through creative projects and empathic reflection, students engaged with the complexities of structural forces that create and maintain health disparities.

Medical students in their clinical years can engage in critical health humanities learning experiences as well. We teach several multidisciplinary electives that address social (in)justice in medicine, as well as mentor fourth-year students engaged in independent electives that foster critical awareness around health equity and ethics.

Beyond the classroom, we have actively engaged in critical health humanities practices through story slams, literary journal clubs, conference presentations, and Grand Rounds. Through these activities we have included learners at GME and CME levels. These examples also demonstrate how community engagement and multidisciplinary partnerships can contribute to the practice of critical health humanities.

Conclusion

In this paper, we explore the growing field of critical health humanities and its potential for teaching health equity through narrative practices. We provide concrete examples of educational activities that incorporate critical consciousness and structural competency – frameworks we have found useful for conceptualizing critical health humanities as a pedagogical practice. We also discuss the strengths and challenges of this work and suggest future directions.
Systematic analysis of hip-preserving treatment for early osteonecrosis of the femoral head from the perspective of bibliometrics (2010–2023)
Authors: Wu Tingyu , Jiang Yaping , Tian Hua , Shi Weipeng , Wang Yingzhen , Li Tao
Published: December 2023

Background

Osteonecrosis of the femoral head (ONFH) is a serious condition that causes bone tissue death, femoral head collapse, and hip joint destruction. Early intervention through hip-preserving treatment is crucial to slow down disease progression, preserve hip joint function, and improve the quality of life of patients. We analyzed the knowledge map, research gaps, and future research directions in the field of hip-preserving treatment for early ONFH.

Methods

All publications related to hip-preserving treatment for early ONFH published between 2010 and 2023 were identified from the Web of Science Core Collection and analyzed using VOSviewer 1.6.19, CiteSpace 6.2.R2, and Scimago Graphica 1.0.35.

Results

In total, 234 articles were analyzed. The results showed an exponential growth trend in the number of publications related to hip-preserving treatment for early ONFH in the past decade. China and the USA were the main contributors. International Orthopaedics published the most papers in this field, whereas Bone and Joint Surgery-American Volume had the highest average citation count per article. Several stable research topics were noted in this field, including core decompression (CD), osteotomy, bone transplantation in hip-preserving surgery, and cell therapy, which have become research hotspots in hip-preserving treatment.

Conclusions

Hip-preserving treatment for early ONFH has received increasing attention, and research in this field is expected to grow. Stable research topics include core decompression (CD), osteotomy, bone transplantation, and cell therapy. Future research is predicted to focus on cell therapy and combination therapy, resulting in an increasing number of publications on hip-preserving treatment for early ONFH.
Efficacy and safety of oral Chinese patent medicines in the treatment of coronary heart disease combined with hyperlipidemia: a systematic review and network meta-analysis of 78 trials
Authors: Yang Zhenyu , Li Jixin , Zhou Bogeng , Ji Xuan , Yuan Jianying , Yan Junchen , Nan Xilei , Guo Dandan
Published: December 2023

Aim of the study

To evaluate the clinical efficacy and safety of commonly used oral Chinese patent medicines for the treatment of coronary heart disease combined with hyperlipidemia in clinical practice through a network meta-analysis.

Materials and methods

PubMed, Embase, Cochrane Library, Web of Science, Wanfang, VIP, SinoMed, and CNKI databases were searched for all published randomized controlled trials (RCTs) on the treatment of coronary heart disease combined with hyperlipidemia using Chinese patent medicines. NoteExpress software was used to screen the literature obtained from the databases according to the inclusion and exclusion criteria. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. A network meta-analysis was performed using R 4.2.1. Subgroup analyses of outcome indicators were made based on conventional treatment (CT) methods. The incidence of adverse events in the included RCTs was statistically analyzed. A funnel plot was drawn using RevMan 5.4.1 software for the assessment of bias in the total clinical effectiveness rate. Finally, the quality of evidence for interventions with statistically significant differences was evaluated using the GRADE system.

Results

A total of 78 RCTs were included, involving 7,955 cases and 8 types of Chinese patent medicines, which were Tongxinluo Capsule, Naoxintong Capsule, Compound Danshen Dripping Pill, Shexiangbaoxin Pill, Songling Xuemaikang Capsule, Xuezhikang Capsule, Yindan Xinnaotong Capsule, and Zhibitai Capsule. A total of 24 RCTs reported the incidence of adverse events, but no statistically significant difference in the incidence of adverse events was found between the experimental and control groups in each study (P > 0.05). There was no obvious publication bias in all studies, but the overall quality of evidence in the included RCTs was low. Comparison of different intervention measures showed that Naoxintong Capsule + CT improved the cardiac index and cardiac output, and lowered the low-density lipoprotein cholesterol and total cholesterol levels. Tongxinluo Capsule + CT raised high-density lipoprotein cholesterol levels and reduced triglyceride levels. Xuezhikang Capsule + CT improved the total clinical effectiveness rate. Subgroup analyses showed that differences in CT did not cause heterogeneity in the results.

Conclusion

Compared with the use of CT alone, the combined use of Chinese patent medicines with CT can effectively improve the symptoms in patients with both coronary heart disease and hyperlipidemia.
Exploring the immune interactions between Oncomelania hupensis and Schistosoma japonicum, with a cross-comparison of immunological research progress in other intermediate host snails
Authors: Li Hongyu , Chen Yihan , Zhu Yunhuan , Feng Yilu , Qian Yuncheng , Ye Xiaoyu , Xu Jiatong , Yang Hanyu , Yu Jiawei , Chen Jingyu , Chen Keda
Published: December 2023

Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of “neglected tropical disease”. Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host’s immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms.

Graphical Abstract
Comprehensive assessment of the genetic characteristics of small for gestational age newborns in NICU: from diagnosis of genetic disorders to prediction of prognosis
Authors: Xiao Hui , Chen Huiyao , Chen Xiang , Lu Yulan , Wu Bingbing , Wang Huijun , Cao Yun , Hu Liyuan , Dong Xinran , Zhou Wenhao , Yang Lin
Published: December 2023

Background

In China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors.

Methods

A cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children’s Hospital of Fudan University, Shanghai, China.

Results

Among the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84–0.96] vs. AUC=0.74 [0.64–0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6–0.93] vs. AUC=0.53[0.29–0.76]; P=0.0117).

Conclusion

SGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.
Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort
Authors: Carrizosa-Molina Tamara , Casillas-Díaz Natalia , Pérez-Nadador Iris , Vales-Villamarín Claudia , López-Martínez Miguel Ángel , Riveiro-Álvarez Rosa , Wilhelm Larry , Cervera-Juanes Rita , Garcés Carmen , Lomniczi Alejandro , Soriano-Guillén Leandro
Published: December 2023

Background

In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort.

Results

We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism.

Conclusions

Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.
Simultaneous surgical management of renal cancer with atrial thrombotic extension and severe chronic coronary artery disease: a case report
Authors: Filomena Giovanni Battista , Marino Filippo , Scarciglia Eros , Russo Pierluigi , Fantasia Fabrizio , Bientinesi Riccardo , Ragonese Mauro , Foschi Nazario , Gulino Gaetano , Sacco Emilio , Racioppi Marco
Published: December 2023

Background

Renal cell carcinoma accounts for 2–3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus.

Case presentation

We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient’s heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day.

Conclusions

Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes.
Sex differences in type 2 diabetes: an opportunity for personalized medicine
Authors: Johnson Meredith L. , Preston Joshua D. , Rashid Cetewayo S. , Pearson Kevin J. , Ham J. Nina
Published: December 2023

Over the past several decades, substantial ground has been gained in understanding the biology of sex differences. With new mandates to include sex as a biological variable in NIH-funded research, greater knowledge is forthcoming on how sex chromosomes, sex hormones, and social and societal differences between sexes can affect the pathophysiology of health and disease. A detailed picture of how biological sex impacts disease pathophysiology will directly inform clinicians in their treatment approaches and challenge canonical therapeutic strategies. Thus, a profound opportunity to explore sex as a variable in personalized medicine now presents itself. While many sex differences are apparent in humans and have been described at length, we are only beginning to see how such differences impact disease progression, treatment efficacy, and outcomes in obesity, type 2 diabetes, and cardiovascular disease. Here, we briefly present the most salient and convincing evidence of sex differences in type 2 diabetes detection, diagnostics, disease course, and therapeutics. We then offer commentary on how this evidence can inform clinicians on how to approach the clinical workup and management of different patients with diabetes. Finally, we discuss some gaps that remain in the literature and propose several research questions to guide basic and translational researchers as they continue in this growing area of scientific exploration.
Protective efficacy of multiepitope vaccines constructed from common antigens of Eimeria species in chickens
Authors: Chen Chen , Su Junzhi , Lu Mingmin , Xu Lixin , Yan Ruofeng , Li Xiangrui , Song Xiaokai
Published: December 2023

Clinical avian coccidiosis is typically caused by coinfection with several Eimeria species. Recombinant protein and DNA vaccines have shown promise in controlling coccidiosis. On this basis, DNA vaccines that encode multiple epitopes from different Eimeria species may provide broad protection against coinfections. In this study, we designed a fusion gene fragment, 14EGT, that contained concentrated T-cell epitopes from four common antigens of Eimeria species (14-3-3, elongation factor 2, glyceraldehyde-3-phosphate dehydrogenase, and transhydrogenase). The multiepitope DNA vaccine pVAX1-14EGT and recombinant protein vaccine pET-32a-14EGT (r14EGT) were then created based on the 14EGT fragment. Subsequently, cellular and humoral immune responses were measured in vaccinated chickens. Vaccination-challenge trials were also conducted, where the birds were vaccinated with the 14EGT preparations and later exposed to single or multiple Eimeria species to evaluate the protective efficacy of the vaccines. According to the results, vaccination with 14EGT preparations effectively increased the proportions of CD4+ and CD8+ T cells and the levels of Th1 and Th2 hallmark cytokines. The levels of serum IgG antibodies were also significantly increased. Animal vaccination trials revealed alleviated enteric lesions, weight loss, and oocyst output compared to those of the control groups. The preparations were found to be moderately effective against single Eimeria species, with the anticoccidial index (ACI) ranging from 160 to 180. However, after challenge with multiple Eimeria species, the protection provided by the 14EGT preparations was not satisfactory, with ACI values of 142.18 and 146.41. Collectively, the results suggest that a multiepitope vaccine that encodes the T-cell epitopes of common antigens derived from Eimeria parasites could be a potential and effective strategy to control avian coccidiosis.
Frailty’s influence on 30-day mortality in old critically ill ICU patients: a bayesian analysis evaluating the clinical frailty scale
Authors: Wernly Bernhard , Bruno Raphael Romano , Beil Michael , Flaatten Hans , Kelm Malte , Sigal Sviri , Szczeklik Wojciech , Elhadi Muhammed , Joannidis Michael , Koköfer Andreas , Oeyen Sandra , Marsh Brian , Moreno Rui , Wernly Sarah , Leaver Susannah , De Lange Dylan W. , Guidet Bertrand , Jung Christian
Published: December 2023

Introduction

Frailty is widely acknowledged as influencing health outcomes among critically ill old patients. Yet, the traditional understanding of its impact has predominantly been through frequentist statistics. We endeavored to explore this association using Bayesian statistics aiming to provide a more nuanced understanding of this multifaceted relationship.

Methods

Our analysis incorporated a cohort of 10,363 older (median age 82 years) patients from three international prospective studies, with 30-day all-cause mortality as the primary outcome. We defined frailty as Clinical Frailty Scale ≥ 5. A hierarchical Bayesian logistic regression model was employed, adjusting for covariables, using a range of priors. An international steering committee of registry members reached a consensus on a minimal clinically important difference (MCID).

Results

In our study, the 30-day mortality was 43%, with rates of 38% in non-frail and 51% in frail groups. Post-adjustment, the median odds ratio (OR) for frailty was 1.60 (95% CI 1.45–1.76). Frailty was invariably linked to adverse outcomes (OR > 1) with 100% probability and had a 90% chance of exceeding the minimal clinically important difference (MCID) (OR > 1.5). For the Clinical Frailty Scale (CFS) as a continuous variable, the median OR was 1.19 (1.16–1.22), with over 99% probability of the effect being more significant than 1.5 times the MCID. Frailty remained outside the region of practical equivalence (ROPE) in all analyses, underscoring its clinical importance regardless of how it is measured.

Conclusions

This research demonstrates the significant impact of frailty on short-term mortality in critically ill elderly patients, particularly when the Clinical Frailty Scale (CFS) is used as a continuous measure. This approach, which views frailty as a spectrum, enables more effective, personalized care for this vulnerable group. Significantly, frailty was consistently outside the region of practical equivalence (ROPE) in our analysis, highlighting its clinical importance.
Evidence at source for the mid-fifteenth century eruption of Kuwae, Vanuatu
Authors: Ballard Chris , Bedford Stuart , Cronin Shane J. , Stern Sönke
Published: December 2023

The mid-fifteenth century eruption of the Kuwae volcano (Vanuatu), known locally as the Tombuk eruption, is widely but not universally considered responsible for one of the three largest atmospheric sulphate events of the past millennium. Questions remain about its precise magnitude and global signature. This controversy reflects a lack of modern description and characterisation of the eruption at source. Through a comprehensive survey of the published and unpublished literature, we review the available historical, archaeological and volcanological evidence for the Kuwae eruption. All sources suggest an eruption with major impacts regionally. The eruption formed a submarine caldera, collapsing the former landmass of Kuwae and leaving two smaller adjacent islands, Epi and Tongoa. On other islands to the immediate south and north, volcanic impacts were variable, enabling survival of refugees from Kuwae, who later recolonised the remnant islands. This review raises hypotheses and questions to be tested through a new multi-disciplinary field research program that aims to establish the precise date and magnitude of the Tombuk eruption, allowing questions of global impact to be addressed with more confidence.
Attributes of errors, facilitators, and barriers related to rate control of IV medications: a scoping review
Authors: Park Jeongok , You Sang Bin , Ryu Gi Wook , Kim Youngkyung
Published: December 2023

Background

Intravenous (IV) medication is commonly administered and closely associated with patient safety. Although nurses dedicate considerable time and effort to rate the control of IV medications, many medication errors have been linked to the wrong rate of IV medication. Further, there is a lack of comprehensive studies examining the literature on rate control of IV medications. This study aimed to identify the attributes of errors, facilitators, and barriers related to rate control of IV medications by summarizing and synthesizing the existing literature.

Methods

This scoping review was conducted using the framework proposed by Arksey and O’Malley and PRISMA-ScR. Overall, four databases—PubMed, Web of Science, EMBASE, and CINAHL—were employed to search for studies published in English before January 2023. We also manually searched reference lists, related journals, and Google Scholar.

Results

A total of 1211 studies were retrieved from the database searches and 23 studies were identified from manual searches, after which 22 studies were selected for the analysis. Among the nine project or experiment studies, two interventions were effective in decreasing errors related to rate control of IV medications. One of them was prospective, continuous incident reporting followed by prevention strategies, and the other encompassed six interventions to mitigate interruptions in medication verification and administration. Facilitators and barriers related to rate control of IV medications were classified as human, design, and system-related contributing factors. The sub-categories of human factors were classified as knowledge deficit, performance deficit, and incorrect dosage or infusion rate. The sub-category of design factor was device. The system-related contributing factors were classified as frequent interruptions and distractions, training, assignment or placement of healthcare providers (HCPs) or inexperienced personnel, policies and procedures, and communication systems between HCPs.

Conclusions

Further research is needed to develop effective interventions to improve IV rate control. Considering the rapid growth of technology in medical settings, interventions and policy changes regarding education and the work environment are necessary. Additionally, each key group such as HCPs, healthcare administrators, and engineers specializing in IV medication infusion devices should perform its role and cooperate for appropriate IV rate control within a structured system.
Prevalence of herbal and traditional medicine in Ethiopia: a systematic review and meta-analysis of 20-year studies
Authors: Tuasha Nigatu , Fekadu Sintayehu , Deyno Serawit
Published: December 2023

Background

The widely accepted prevalence of traditional medicine (TM) in Ethiopia was about 80 %, of which 95 % were sourced from plants. The purpose of this study was to update knowledge of the prevalence of herbal medicine or TM in Ethiopia and describe the characteristics of the population mostly relying on herbal medicine or TM to inform health policy-makers.

Methods

PubMed, Google Scholar, Hinari, Scopus, and the Directory of Open Access Journals (DOAJ) were searched. The methodological quality of each included study was assessed using the quality assessment checklist for prevalence studies. Meta-analysis was conducted using STATA version 17, and the heterogeneity between studies was assessed using I2 test statistics based on the random effect model. Forest and funnel plots were used to present the data. Subgroup analysis was done by the study population, region, and setting.

Results

Thirty-six studies with a total of 16,288 participants met the inclusion criteria. Meta-analysis of the study revealed that the prevalence of herbal medicine use in Ethiopia is 46 % (95 % CI, 37–54 %), with significant heterogeneity among the studies (I2 = 99.19 %). Egger’s test for publication bias of herbal medicine use revealed significant results (Egger, P = 0.002) which indicates possible missing of small sample size studies. The prevalence of TM use in Ethiopia is 65 % (95 % CI, 52–77 %) with significant heterogeneity among the studies (I2 = 99.18 %). Egger’s test for publication bias of TM use revealed non-significant results (Egger, P = 0.275). The subgroup analysis by the study setting and the region revealed variability amongst the studies. Community-based studies and Oromia National Regional State showed higher prevalence. By population type, a higher prevalence of TM use was observed amongst children and lowest amongst malaria suspects.

Conclusions

The current study revealed that TM/herbal medicine utilization remained an important source of primary healthcare in Ethiopia. In comparison to the commonly reported prevalence of TM/herbal medicine, there is a considerable decline in TM/herbal medicine prevalence. High TM/herbal medicine use tendency during pregnancy necessitates safety studies to optimize the utilization.
Radial solutions of p-Laplace equations with nonlinear gradient terms on exterior domains
Authors: Li Yongxiang , Li Pengbo
Published: December 2023

This paper studies the existence of radial solutions of the boundary value problem of p-Laplace equation with gradient term $$ \textstyle\begin{cases} -\Delta_{p} u= K( \vert x \vert ) f( \vert x \vert , u, \vert \nabla u \vert ) ,\quad x\in\Omega , \\ \frac{\partial u}{\partial n}=0 ,\quad x\in\partial\Omega, \\ \lim_{ \vert x \vert \to\infty}u(x)=0 , \end{cases} $$

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Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA
Authors: Zhong Hao-Jie , Wang Si-Qi , Zhang Ruo-Xin , Zhuang Yu-Pei , Li Longyan , Yi Shuo-Zhao , Li Ying , Wu Lei , Ding Yu , Zhang Jumei , Xie Xinqiang , He Xing-Xiang , Wu Qingping
Published: December 2023

Background

The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the “enteric nervous system–vagus nerve–brain” axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure.

Methods

Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice.

Results

The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system.

Conclusions

These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.
Considerations for the genotoxicity assessment of middle size peptide drugs containing non-canonical amino acid residues
Authors: Mishima Masayuki , Sugiyama Kei-ichi
Published: December 2023

Background

Middle size peptides (MSPs) have emerged as a promising new pharmaceutical modality. We are seeking the best way to assess the non-clinical safety of MSPs.

Consideration

The requirements for assessing the genotoxicity of pharmaceuticals differ between small molecule drugs and biotherapeutics. Genotoxicity tests are necessary for small molecule drugs but not for biotherapeutics. MSPs, however, share similarities with both small molecule drugs and biotherapeutics. Here, we describe important points to consider in assessing the genotoxicity of MSP drugs. The current standard of genotoxicity assessment for small molecules may not be entirely appropriate for MSP drugs. MSP drugs need genotoxicity assessment mostly according to the current standard of small molecule drugs.

Conclusion

We propose a few modifications to the standard test battery of genotoxicity tests, specifically, the inclusion of an in vitro gene mutation test using mammalian cells, and exclusion of (Q)SAR assessment on MSP-related impurities.
Efficacy of single burr hole with irrigation and sub-dural drain in the evacuation of chronic subdural hematoma
Authors: Gomaa Mahmoud Ahmed , Osman Ashraf Abdellatif , Aboelhuda Ahmed Hosameldin
Published: December 2023

Background

Chronic subdural hematoma (CSDH) remains one of the most common types of traumatic and spontaneous intracranial hematomas. The optimal method of treatment has not been definitely established. Surgical treatment options includes craniotomy, trephination, burrhole drainage and twist drill perforation. This study aimed at the evaluation of the clinical and radiological outcome after the efficacy of single burr hole with irrigation and sub-dural drain in the aim of successful evacuation of CSDH.

Results

A total of 53 patients were included in this study, the mean age of patients was 61.53 + 13.81 years. Results of the paired t test showed that the Glasgow coma scale has significantly improved by 0.89 points (p < 0.001) and that the average motor power has significantly improved for all individuals by 0.4 points (p = 0.043). We found that older aged patients have significantly less improvements in the postoperative motor power (r = − 0.317, p = 0.02) and require longer hospital stay (r = 0.32, p = 0.0197).

Conclusions

A single burr hole with irrigation and leaving a subdural drain is safe procedure in managing subdural hematoma. We did not experience major adverse events related to drain insertion and efficient evacuation of collection and no obvious increase in mortality or morbidity rates.