bluuebunny/crossref_metadata_2025 huggingface dataset:
Paralytic ileus in a patient on clozapine therapy showing an inverted clozapine/norclozapine ratio after switching valproic acid to carbamazepine: a case report
Authors: van Weringh Geke , van Koolwijk Leonieke , Haan Lieuwe de , Touw Daan J. , de Koning Mariken B.
Published: May 2024

This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.
Mechanisms of Change in School Counseling Intervention Studies: A Content Analysis
Authors: Kim Hyunhee , Lemberger-Truelove Matthew E. , Wills LeAnn N. , Basner Elishia J. , Tipton Jennifer L.
Published: May 2024

The purpose of this content analysis was to examine the use of theory in school-counselor-led interventions. Specifically, we examined intervention characteristics, evaluation design, and use of theory in school-counselor-led intervention studies that were published by the American Counseling Association, the American School Counselor Association (ASCA), and in other school-counseling-related journals from 2003 to 2022. Drawing from 45 published articles, results indicated that few school counseling articles explicitly included ASCA Mindsets & Behaviors (ASCA, 2021) or integrated formal counseling theory to inform student outcomes.
Breaking Down Barriers: The Moderating Role of Organizational Support in Facilitating Knowledge Sharing Among Software Developers
Authors: Anwar Rayhab , Rehman Mobashar , Rehman Hafiz Mudassir , Nauman Shazia , Khan Ayesha Sarwar , Malik Mustafa
Published: May 2024

Effective knowledge sharing among software developers is crucial for maximizing software development output throughout the software development lifecycle. Building upon Triandis’ Facilitating condition, this study explores the moderating impact of two factors, namely Organizational support and Technological support, on the relationship between knowledge sharing intentions (KSI) and knowledge sharing behavior (KSB). Specifically, the study investigates the impact of KSB on individuals’ job performance in global software development organizations. A self-administered questionnaire was used to collect data from 302 Malaysian participants working on global software development projects. The collected data was analyzed using Structure Equation Modeling (SEM) through SmartPLS. The results reveal that only organizational support, among Triandis’ Facilitating conditions, moderates the relationship between KSI and KSB. Moreover, the study finds that KSB mediates the relationship between knowledge sharing intentions and job performance. The findings of this study provide practical and theoretical implications for software developers.
Migrant Status and Consumer Financial Fraud in China: A Two-Stage Approach Using a Representative Household Survey
Authors: Yu Zhou , Fan Jessie X.
Published: May 2024

Chinese migrants face numerous socioeconomic disadvantages. Little is understood about their vulnerability to consumer financial fraud, which can impede their integration into urban China and hamper the national priority of continued urbanization. This study utilizes nationally representative data from 2015 China Household Finance Survey to investigate migrants’ risk factors for consumer financial fraud across two stages: fraud exposure and victimization. Results reveal a distinct pattern of fraud risks based on migrant status and stages of fraud, partially supporting theories of disadvantaged consumer and routine activity. After adjusting for other factors, urban migrants exhibit a 28.2% higher likelihood of encountering fraud than urban residents, with rural migrants having a 57.3% higher probability of overall victimization. Recent movers face a higher risk. Market and digital engagement emerge as key factors influencing fraud exposure. These results underscore the necessity for targeted policy interventions aimed at fostering inclusive urbanization and promoting rural-urban integration.
Does Knowledge Retention Mediate Training Content, Training Needs Analysis on Sustainable  Development in Oman Higher Education Institution?
Authors: Ugheoke Solomon Ozemoyah , Shrivastava Preeti , Mashi Munir Shehu , Siju Nitha
Published: May 2024

To date, little research has examined the human resources side of sustainability. To bridge this gap, we examined human resource management (HRM) practices and sustainable development in the micro-level higher education context in Oman. Quantitative research was used to test the predictors of sustainable development. We received 347 responses from employees working in 10 higher education institutions (HEIs) in Oman. The structural as well as measurement model was calculated using SmartPLS. The result showed that training is a unique source of creating sustainability. The mediating effect of knowledge retention was found to play a significant role in this relationship. We found that many HEIs need to do more to make employees understand the importance of their contribution to the achievement of this goal. HEIs play a significant role in the development as well as implementation of sustainable practices. Significantly, we enrich the understanding of the emerging universal wave of sustainability by identifying how vital HRM practices impact sustainable development from an academic and professional perspective. The study is restricted to Oman, but the research impact and applicability may be conducted in another environment or sectors. Sustainability and knowledge retention in HEIs are paramount issues for everyone.
Assessing the Impact of Social Determinants of Health on HIV Care Engagement in the Southern United States: A Cross-Sectional Study
Authors: Sohail Maira , Cleveland John D. , McCollum C. Greer , Burgan Kaylee W. , Hearld Larry R. , Carodine Alyssa , Johnson Kendra , Fort Melvin , Thompson Jennifer , Mugavero Michael J.
Published: May 2024

Recent studies have shown social determinants of health (SDOH) to impact HIV care engagement. This cross-sectional study (Oct 20-Apr 21) assessed the impact of a range of SDOH on HIV care engagement using data from HIV Care Connect, a consortium of three HIV care facility-led programs (Alabama, Florida, Mississippi). The exposures were captured using the PRAPARE (Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences) scale. The outcome was captured using the Index of Engagement in HIV Care scale. Participants (n  =  132) were predominantly non-White (87%) and male (52%) with a median age of 41 years. Multivariable logistic regression adjusted for various sociodemographics showed lower HIV care engagement to be associated with being uninsured/publicly insured, having 1-3 unmet needs, socially integrating ≤five times/week, and having stable housing. Factors such as unmet needs, un-/underinsurance, and social integration may be addressed by healthcare and community organizations.
Evaluation of Nurse Navigator Support for Patients During Telehealth Neurosurgery Clinics
Authors: Critchley Giles , Harvey Phylis , Saunders Rose , John Simon , Todd Keith
Published: May 2024

Telehealth clinics have been used in many specialities, including neurosurgery, to improve access for patients in rural communities. The introduction of nurse navigators involved with the patient before, during and after the clinic was evaluated. Clinics were held in a rural hospital with a nurse navigator present in the clinic with the patient, and the physician consulting remotely. A patient satisfaction survey and audit were conducted following ten telehealth clinics. Twenty-one new patients were able to be contacted out of 31 (68%) with an 11 question structured survey. Eighteen out of 21 (86%) stated they were satisfied with the quality of the clinic compared with an in-person clinic. Overall satisfaction scores of 7–10 were scored by 18/21 patients (86%) on a scale of 1–10. An estimated 10785 km of travel was saved for patients going to a rural hospital clinic rather than the neurosurgical centre. This study shows that the supportive role of nurse navigators throughout the patient telehealth clinic pathway merits further continuing evaluation.
Assessing Credibility: Quality Criteria for Patients, Caregivers, and the Public in Online Health Information—A Qualitative Study
Authors: Daraz Lubna , Dogu Cicek , Houde Virginie , Bouseh Sheila , Morshed Knondoker G
Published: May 2024

The increasing reliance on the Internet for health information has raised concerns about patients using unreliable and potentially harmful content. This study aimed to establish quality criteria to assist patients, caregivers, and the public in evaluating the reliability of online health information. We conducted focus group workshops with 25 participants recruited across Canada, proficient in either English or French. The participants included 13 females and 12 males, with the majority having a college or higher level of education. Through an in-depth analysis comparing various aspects, the participants determined 6 quality criteria: authorship, reliability, usefulness, accessibility, readability, and privacy & confidentiality. The findings from this study present a comprehensive list of quality criteria that will contribute to developing evidence-based quality benchmarks and policy frameworks in multiple languages. These criteria are not only valid but also well-suited to the diverse needs and preferences of patients and the public, providing a reliable framework for evaluating online health information through an evidence-based approach.
Relationship between the built environment and urban vitality of Nanjing’s central urban area based on multi-source data
Authors: Qin Jiarui , Wang Ziyang , Sheng Yehua , Xue Li , Cai Xiaolan , Zhang Ka
Published: May 2024

Urban vitality reflects the dynamism, openness, available resources, and linkages between different elements in a city. Many studies have focused on the relationship between urban vitality and the built environment, which can benefit urban planners. Based on multi-source data, this study incorporates the aspects of economy, society, culture, and innovation to comprehensively measure urban vitality. Recognizing the significant influence of the built environment on urban vitality, this paper takes Nanjing as the study area. It explores the relationship between urban vitality and the built environment using ordinary least squares and multi-scale geographically weighted regression models based on multi-source data. The results reveal multi-centered urban vitality within Nanjing’s central urban area, which gradually decreases outwards from the city center. Particularly, the southern region has a higher comprehensive vitality than the northern region. While differences in vitality between dimensions are evident, an overall consistent pattern emerges. The spatial distribution of influence varies across different spatial factor. The method provided in this study gives a new view of urban vitality measurement and evaluation.
The combination of Asp519Val/Glu665Val and Lys1813Ala mutations in FVIII markedly increases coagulation potential
Authors: Nakajima Yuto , Oda Akihisa , Baatartsogt Nemekhbayar , Kashiwakura Yuji , Ohmori Tsukasa , Nogami Keiji
Published: May 2024

A2 domain dissociation in activated factor VIII (FVIIIa) results in reduced activity. Previous studies demonstrated that some FVIII mutants (D519V/E665V and K1813A) with delayed A2 dissociation enhanced coagulation potential. We speculated, therefore, that FVIII encompassing a combination of these mutations might further enhance coagulant activity. The aim was to assess the D519V/E665V/K1813A-FVIII mutation as a gain of function. The FVIII mutants, D519V/E665V/K1813A, D519V/E665V, and K1813A were expressed in a baby hamster kidney cell system, and global coagulation potential of these mutants was compared with wild-type (WT) FVIII in vitro and in hemophilia A mice in vivo. Kinetic analyses indicated that the apparent Kd for FIXa on the tenase assembly with D519V/E665V and D519V/E665V/K1813A mutants were lower, and that the generated FXa for D519V/E665V/K1813A was significantly greater than WT-FVIII. WT-FVIII activity after thrombin activation increased by ∼12-fold within 5 minutes, and returned to initial levels within 30 minutes. In contrast, The FVIII-related activity of D519V/E665V/K1813A increased further with time after thrombin activation, and showed an ∼25-fold increase at 2 hours. The A2 dissociation rate of D519V/E665V/K1813A was ∼50-fold slower than the WT in a 1-stage clotting assay. Thrombin generation assays demonstrated that D519V/E665V/K1813A (0.125 nM) exhibited coagulation potential comparable with that of the WT (1 nM). In animal studies, rotational thromboelastometry and tail-clip assays showed that the coagulation potential of D519V/E665V/K1813A (0.25 μg/kg) was equal to that of the WT (2 μg/kg). FVIII-D519V/E665V/K1813A mutant could provide an approximately eightfold increase in hemostatic function of WT-FVIII because of increased FVIIIa stability and the association between FVIIIa and FIXa.
Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis
Authors: Gerds Aaron T. , Harrison Claire , Kiladjian Jean-Jacques , Mesa Ruben , Vannucchi Alessandro M. , Komrokji Rami , Bose Prithviraj , Kremyanskaya Marina , Mead Adam J. , Gotlib Jason , Rose Shelonitda , Sanabria Fabian , Marsousi Niloufar , Giuseppi Ana Carolina , Jiang Huijing , Palmer Jeanne M. , McCaul Kelly , Ribrag Vincent , Passamonti Francesco
Published: May 2024

The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non–transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542.
Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015–2019: the RECUR Germany study
Authors: Antunes Ana , Tricotel Aurore , Wilk Adrian , Dombrowski Silvia , Rinta-Kokko Hanna , Andersson Fredrik L. , Ghosh Subrata
Published: May 2024

Background

Clostridioides difficile infections (CDIs) and recurrences (rCDIs) remain a major public health challenge due to substantial mortality and associated costs. This study aims to generate real-world evidence on the mortality and economic burden of CDI in Germany using claims data between 2015 and 2019.

Methods

A longitudinal and matched cohort study using retrospective data from Statutory Health Insurance (SHI) was conducted in Germany with the BKK database. Adults diagnosed with CDI in hospital and community settings between 2015 and 2018 were included in the study. Patients had a minimum follow-up of 12-months. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients matched by demographic and clinical characteristics was used to assess excess mortality and incremental costs of HCRU. Up to three non-CDI patients were matched to each CDI patient.

Results

A total of 9,977 CDI patients were included in the longitudinal cohort. All-cause mortality was 32%, 39% and 48% at 6-, 12-, and 24-months, respectively, with minor variations by number of rCDIs. When comparing matched CDI (n = 5,618) and non-CDI patients (n = 16,845), CDI patients had an excess mortality of 2.17, 1.35, and 0.94 deaths per 100 patient-months, respectively. HCRU and associated costs were consistently higher in CDI patients compared to non-CDI patients and increased with recurrences. Total mean and median HCRU cost per patient during follow-up was €12,893.56 and €6,050 in CDI patients, respectively, with hospitalisations representing the highest proportion of costs. A total mean incremental cost per patient of €4,101 was estimated in CDI patients compared to non-CDI patients, increasing to €13,291 in patients with ≥ 3 rCDIs.

Conclusions

In this real-world study conducted in Germany, CDI was associated with increased risk of death and substantial costs to health systems due to higher HCRU, especially hospitalisations. HCRU and associated costs were exacerbated by rCDIs.
Rotavirus vaccines in Africa and Norovirus genetic diversity in children aged 0 to 5 years old: a systematic review and meta-analysis
Authors: Dakouo Dako , Ouermi Djénéba , Ouattara Abdoul Karim , Simpore Abibou , Compaore Tégwendé Rebecca , Traore Mah Alima Esther , Gamsore Zakaria , Zoure Abdou Azaque , Traore Lassina , Zohoncon Théodora Mahoukèdè , Yonli Albert Théophane , Ilboudo P. Denise , Djigma Florencia Wendkuuni , Simpore Jacques
Published: May 2024

Noroviruses are the second leading cause of death in children under the age of 5 years old. They are responsible for 200 million cases of diarrhoea and 50,000 deaths in children through the word, mainly in low-income countries. The objective of this review was to assess how the prevalence and genetic diversity of noroviruses have been affected by the introduction of rotavirus vaccines in Africa. PubMed, Web of Science and Science Direct databases were searched for articles. All included studies were conducted in Africa in children aged 0 to 5 years old with gastroenteritis. STATA version 16.0 software was used to perform the meta-analysis. The method of Dersimonian and Laird, based on the random effects model, was used for the statistical analyses in order to estimate the pooled prevalence’s at a 95% confidence interval (CI). Heterogeneity was assessed by Cochran’s Q test using the I2 index. The funnel plot was used to assess study publication bias. A total of 521 studies were retrieved from the databases, and 19 were included in the meta-analysis. The pooled norovirus prevalence’s for pre- and post-vaccination rotavirus studies were 15% (95 CI, 15–18) and 13% (95 CI, 09–17) respectively. GII was the predominant genogroup, with prevalence of 87.64% and 91.20% respectively for the pre- and post-vaccination studies. GII.4 was the most frequently detected genotype, with rates of 66.84% and 51.24% respectively for the pre- and post-vaccination studies. This meta-analysis indicates that rotavirus vaccination has not resulted in a decrease in norovirus infections in Africa.
Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice
Authors: Moshfeghi Andrew A. , Khurana Rahul N. , Moini Hadi , Sherman Steven , Reed Kimberly , Boucher Nick , Rahimy Ehsan
Published: May 2024

Background

This study evaluated impact of anti–vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice.

Methods

This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan–Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment.

Results

Among anti-VEGF–naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65–2.72) for moderate vs mild NPDR and 6.51 (6.47–6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%–8.3%), 20.9%, (20.0%–21.7%) and 46.8% (44.4%–49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7–1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4–0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4–0.7]) compared with 49.9% in eyes with no treatment (n = 8930).

Conclusions

DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.
Adolescent boys’ experiences of mental health and school health services - an interview study from Norway
Authors: Helland Lindborg Tonje , Kristensson Hallström Inger , Synnøve Litland Astrid , Åvik Persson Helene
Published: May 2024

Background

Mental health problems among adolescents is a global challenge. During the transition to adolescence, physiological, psychological, and social changes occur, leading to increased vulnerability. Thus, adolescent boys are less likely to seek help for mental health problems, which makes them an undetected group. The aim of this study was to gain a deeper understanding of adolescent boys’ experiences of mental health and school health service.

Methods

An inductive, qualitative design was chosen using three focus group interviews and three individual interviews. The study included 18 adolescent boys in 7th grade, in a school located in a medium-sized municipality in Norway. The interviews were analysed with qualitative content analysis. The consolidated criteria for reporting qualitative research (COREQ) were followed in this study.

Results

The overall theme “barriers towards seeking help”, and three categories— navigating stigma and privacy concerns; perceptions of self-responsibility; and lacking knowledge of mental health problems and help-seeking—described the adolescent boys experiences. The awareness and willingness to seek help were present, but there are barriers preventing the adolescent boys from acting on that willingness.

Conclusions

Lack of knowledge and a non-permissive culture for mental health problems among adolescents contributes to decreased help-seeking behaviour among adolescent boys. The school health service is the most related health service for adolescents and should focus on being available and strengthening empowerment and mental health literacy through the development and implementation of interventions to promote mental health.
Association of frailty status with overall survival in elderly hypertensive patients: based on the Chinese Longitudinal Healthy Longevity Survey
Authors: Li Liying , Liang Yueting , Xin Dajun , Liu Lu , Tan Zhuomin , Wang Ziqiong , Zhang Muxin , Ruan Haiyan , Zhao Liming , Wang Kexin , Zheng Yi , Song Ningying , He Sen
Published: May 2024

Background

Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey.

Methods

A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 < FI ≤ 0.20), mild-frailty (0.20 < FI ≤ 0.30), and moderate-severe frailty (FI > 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival.

Results

During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80–0.87) for the pre-frailty group, 0.68 (95% CI: 0.64–0.72) for the mild frailty group, and 0.52 (95% CI: 0.48–0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82–0.85). Stratified and sensitivity analyses suggested the robustness of the results.

Conclusions

The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.
Update on the practice of premarital screening for sickle cell traits in Africa: a systematic review and meta-analysis
Authors: Dilli Priscilla Peter , Obeagu Emmanuel , Tamale Andrew , Ajugwo Anselm , Pius Theophilus , Makeri Danladi
Published: May 2024

Background

Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening.

Methods

This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits.

Results

Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53–49.11]; I2: 98.95% [98.74–99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (β = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables.

Conclusion

With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.
The effect of artificial saliva on the control of dry mouth: a semi-experimental study on COVID-19 patients under Non-invasive mechanical ventilation
Authors: Sedighi Ladan , Khari Sorour , Hasheminik Morteza , Salimi Akinabadi Atefe , Alipour Haleh , Shafigh Elnaz , Shafigh Navid
Published: May 2024

Objectives

Since maintaining oral hygiene is essential in nursing care, the present study was conducted to determine the effect of oral care using Mucosamin artificial saliva spray to control dry mouth in ICU patients with COVID-19.

Materials and methods

The current semi-experimental research was conducted on eighty patients with COVID-19 selected using the available sampling method. The study tool was a Beck oral assessment scale (BOAS). The case and control groups were selected from two hospitals with relatively similar conditions and treatment procedures. For patients in the intervention group, mucosamin artificial saliva spray was used in addition to the common care, while control group patients received only common care.

Results

Eighty patients were randomly assigned to two groups named control and intervention (40 patients in each group). The intervention was very effective in reducing the BOAS score after four days in comparison with the control group (9.23 vs. 12.05, respectively; p-value < 0.001). Based on the adjusted model, the application of artificial saliva reduced the BOAS score, indicating improvement in mouth dryness. While the BOAS score was increased in the control group, it had a declining trend in the intervention one.

Conclusion

The study’s results showed that using artificial saliva spray could effectively reduce the symptoms of dry mouth in patients with COVID-19 treated with non-invasive mechanical ventilation.

Clinical relevance

The present study introduced an applicable solution (artificial saliva) to treat mouth dryness in ICU patients under mechanical ventilation.
M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis
Authors: Fan Chunyang , Wang Wei , Yu Zilin , Wang Jiale , Xu Wei , Ji Zhongwei , He Wei , Hua Di , Wang Wentao , Yao Linye , Deng Yongkang , Geng Dechun , Wu Xiexing , Mao Haiqing
Published: May 2024

Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-β-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-β-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy.

Graphical Abstract
Impact of extracorporeal membrane oxygenation treatments on acquired von Willebrand syndrome in patients with out-of-hospital cardiac arrest: a retrospective observational study
Authors: Chiba Yuki , Goto Kota , Suzuki Misako , Horiuchi Hisanori , Hayakawa Mineji
Published: May 2024

Background

Von Willebrand factor (vWF) plays a crucial role in hemostasis, acting as a key factor for platelet adhesion/aggregation and as a transport protein for coagulation factor VIII. vWF is secreted as a giant multimer, and it undergoes shear stress-dependent cleavage by a specific metalloproteinase in plasma. Among vWF multimers, high-molecular-weight (large) multimers are essential for hemostasis. Acquired von Willebrand syndrome, linked to various conditions, is a hemostatic disorder due to reduced vWF activity. Extracorporeal membrane oxygenation (ECMO), utilized recently for out-of-hospital cardiac arrest patients, generates high shear stress inside the pump. This stress may induce a conformational change in vWF, enhancing cleavage by a specific metalloproteinase and thereby reducing vWF activity. However, no study has investigated the effects of ECMO on vWF-related factors in patients receiving or not receiving ECMO. This study aimed to elucidate the relationship between ECMO treatment and acquired von Willebrand syndrome-related factors in patients with out-of-hospital cardiac arrest.

Methods

This study included patients with cardiogenic out-of-hospital cardiac arrest admitted to our hospital. The patients were categorized into two groups (ECMO and non-ECMO) based on the presence or absence of ECMO treatment. Plasma samples were collected from patients admitted to the emergency department (days 0–4). The vWF antigen (vWF: Ag), vWF ristocetin cofactor activity (vWF: RCo), and factor VIII activity were measured. Additionally, a large multimer of vWF was evaluated through vWF multimer analysis, utilizing western blotting to probe vWF under non-reducing conditions.

Results

The ECMO and non-ECMO groups included 10 and 22 patients, respectively. The median ECMO treatment in the ECMO group was 64.6 h. No differences in vWF: Ag or factor VIII activity were observed between the two groups during the observation period. However, the ECMO group exhibited a decrease in large vWF multimers and vWF: RCo during ECMO. Strong correlations were observed between vWF: RCo and vWF: Ag in both groups, although the relationships were significantly different between the two groups.

Conclusions

ECMO treatment in patients with out-of-hospital cardiac arrest resulted in the loss of large vWF multimers and decreased vWF activity. Hence, decreased vWF activity should be considered as a cause of bleeding during ECMO management.
The associations of adherence to the Mediterranean diet with chronic dizziness and imbalance in community-dwelling adults: KNHANES 2019–2021
Authors: Jeong Seong-Hae , Kim Eun Ji , Kwon Eunjin , Kim Ji-Soo , Jung Sukyoung
Published: May 2024

Background

Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of life, but also increase mortality. While the Mediterranean diet has long been considered beneficial for human and planetary health, its effects on chronic dizziness or imbalance are understudied. We investigated the associations of adherence to the Mediterranean diet with chronic dizziness and imbalance.

Methods

This study used data from the Korea National Health and Nutrition Examination Survey 2019–2021 and included 4,183 adults aged 40 years and older with complete information from diet, dizziness, and neurotology questionnaires. The alternate Mediterranean diet score (aMed) for nine food groups was calculated from 24-hour dietary recall data. Based on questionnaire responses, chronic dizziness was categorized as either isolated or chronic dizziness with imbalance, characterized by a cluster of difficulties maintaining a standing position, walking, or falling.

Results

In a multivariable-adjusted model, the prevalence of chronic imbalance was lower in the top aMed tertile than in the bottom tertile (OR 0.37; 95% CI, 0.18–0.74; p-trend = 0.01). Among the individual aMed components, the intake of whole grains and nuts exhibited an inverse relationship with chronic imbalance (OR 0.50; 95% CI, 0.27–0.93 for whole grains; OR 0.55; 95% CI, 0.31–1.01 for nuts). The aMed score was not associated with isolated chronic dizziness.

Conclusions

Greater adherence to the Mediterranean diet may reduce chronic imbalance, particularly with an adequate intake of whole grains and nuts.
Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables
Authors: Wu Guanrong , Hu Yijun , Zhu Qibo , Liang Anyi , Du Zijing , Zheng Chunwen , Liang Yanhua , Zheng Yuxiang , Hu Yunyan , Kong Lingcong , Liang Yingying , Amadou Maman Lawali Dan Jouma , Fang Ying , Liu Yuejuan , Feng Songfu , Yuan Ling , Cao Dan , Lin Jinxin , Yu Honghua
Published: May 2024

Objective

Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario.

Methods

In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People’s Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People’s Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction.

Results

The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively.

Conclusion

The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.
Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses
Authors: Larkin Riley M. , Lopez Diana C. , Robbins Yvette L. , Lassoued Wiem , Canubas Kenneth , Warner Andrew , Karim Baktiar , Vulikh Ksenia , Hodge James W. , Floudas Charalampos S. , Gulley James L. , Gallia Gary L. , Allen Clint T. , London Nyall R.
Published: May 2024

Background

Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches.

Methods

Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed.

Results

A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration.

Conclusion

These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.
The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV)
Authors: Movahed Fatemeh , Darzi Satinik , Mahdavi Parya , Salih Mahdi Morug , Qutaiba B. Allela Omer , Naji Sameer Hayder , Adil Mohaned , Zarkhah Hasna , Yasamineh Saman , Gholizadeh Omid
Published: May 2024

Cervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique to the virus have been an affordable way to manage viral diseases. CC risk is decreased, but not eliminated, by HPV vaccinations. Since vaccinations have been made available globally, almost 90% of HPV infections have been successfully avoided. On the lesions and diseases that are already present, however, no discernible treatment benefit has been shown. As a result, therapeutic vaccines that elicit immune responses mediated by cells are necessary for the treatment of established infections and cancers. mRNA vaccines possess remarkable potential in combating viral diseases and malignancy as a result of their superior industrial production, safety, and efficacy. Furthermore, considering the expeditiousness of production, the mRNA vaccine exhibits promise as a therapeutic approach targeting HPV. Given that the HPV-encoded early proteins, including oncoproteins E6 and E7, are consistently present in HPV-related cancers and pre-cancerous lesions and have crucial functions in the progression and persistence of HPV-related diseases, they serve as ideal targets for therapeutic HPV vaccines. The action mechanism of HPV and HPV-related cancer mRNA vaccines, their recent advancements in clinical trials, and the potential for their therapeutic applications are highlighted in this study, which also offers a quick summary of the present state of mRNA vaccines. Lastly, we highlight a few difficulties with mRNA HPV vaccination clinical practice and provide our thoughts on further advancements in this quickly changing sector. It is expected that mRNA vaccines will soon be produced quickly for clinical HPV prevention and treatment.

Graphical Abstract