bluuebunny/crossref_metadata_2025 huggingface dataset:
People who inject oral morphine favor experimentation with injectable opioid substitution
Authors: Bertin Célian , Dècle Philémon , Chappard Pierre , Roux Perrine , Authier Nicolas
Published: September 2023

Background

The French Addictovigilance network has observed the existence of the intravenous use of oral morphine capsules among people suffering from opioid use disorders. According to persons who inject morphine, these capsules are easy to dissolve and then inject, giving them the image of an "injectable" opioid substitution treatment (OST). In France, validated OSTs are only available orally, so dissolving morphine capsules represents the only alternative for patients who are not sufficiently relieved by oral forms.

This practice presents risks related to the potential persistence of particles of the oral galenic in the injectable solution, despite its filtration, but also risks—notably of overdose—related to the pharmacological effects of opioids and to variations of the quantities of morphine extracted during the dissolution of the capsules. We conducted an online survey among the people concerned to collect data on their needs and expectations regarding a possible injectable substitution.

Method

An anonymous online survey including all voluntary respondents residing in France and using oral morphine intravenously was conducted in partnership with the Psychoactif harm reduction organization, from 23/03/2020 to 01/04/2021.

Results

The analysis of the 157 exploitable questionnaires showed that 41% of the respondents obtained their drugs only from illegal markets. The others received, regularly or occasionally, medical prescriptions, reimbursed in 84% of cases. For 78% of the respondents, injection was the most frequent route of morphine administration, with 3.8 ± 2 injections per day. 56% of the respondents were receiving an OST, on prescription (79%), monthly (86%), in addition to morphine.

Skenan® capsules were the most frequently used (81%) and 47.2% of the respondents had already experienced injection-related complications. 95% of the respondents were in favor of experimenting with an injectable morphine substitution. Those who never received medical prescriptions were the youngest (< 25 years) respondents, they reported only occasional use of morphine, and always intravenously.

Conclusion

Oral morphine capsules dissolved and injected intravenously are not a safe and sustainable injectable substitution. Respondents wish to be able to benefit from an injectable substitution with a formulation adapted to the intravenous route. The availability of an injectable substitution would facilitate harm reduction and entry into care for the people concerned, particularly the youngest who have never received morphine prescriptions.
Public health impact and harm reduction implications of xylazine-involved overdoses: a narrative review
Authors: Zhu David T.
Published: September 2023

Introduction

Xylazine, an α2-adrenoceptor agonist sedative commonly used in veterinary medicine, is not approved for human use. Nevertheless, xylazine-involved overdose rates have surged in recent years, fueled by an increasingly toxic and synthetic illicit drug supply in North America.

Methods

This narrative review assessed major epidemiological trends in xylazine-involved overdoses in North America, aiming to identify harm reduction priorities. A literature search was conducted using four bibliographic databases (PubMed, Scopus, Embase, and ScienceDirect) and three preprint servers (medRxiv, bioRxiv, and Europe PMC) on May 28, 2023, to capture articles related to combinations of keywords such as “xylazine”, “opioid”, and “harm reduction”.

Results

Xylazine emerged as an adulterant in Puerto Rico in 2001, likely diverted from veterinary supplies. By the mid-2010s, it began proliferating across unregulated US drug markets, often contemporaneously with illicitly manufactured fentanyl (IMF), displaying characteristics of a syndemic. Initially concentrated in Northeastern regions (e.g., Philadelphia, Connecticut, Maryland), xylazine-involved overdoses later extended to the Rust Belt, Southern, and Western regions of the USA in the late 2010s and early 2020s. During this time, xylazine-involved overdoses also surged in Canada, particularly in Western provinces (British Columbia and Alberta) and Ontario with established IMF-dominated unregulated drug markets.

Discussion

Over the past two decades, xylazine-involved overdoses have been rapidly rising in North America and exhibit few signs of slowing down, representing a serious public health epidemic. Numerous factors may have contributed to this, including limited epidemiological surveillance and drug checking for xylazine and emerging novel adulterants; further, barriers to comprehensive, trauma-informed, non-stigmatizing treatment and social services have also exacerbated this issue. While several epidemiological and ethnographic studies have assessed these factors in the USA, limited evidence is available in Canada where xylazine emerged more recently. This underscores the need for additional research and harm reduction measures.

Conclusion

Harm reduction-informed public health guidelines and programs are urgently needed to promote a safer supply, strengthen the healthcare system capacity to prevent and respond to xylazine-involved overdoses, and address social and structural disparities in health outcomes.
The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer
Authors: Bodoque-Villar Raquel , Padilla-Valverde David , González-López Lucía María , Muñoz-Rodríguez José Ramón , Arias-Pardilla Javier , Villar-Rodríguez Clara , Gómez-Romero Francisco Javier , Verdugo-Moreno Gema , Redondo-Calvo Francisco Javier , Serrano-Oviedo Leticia
Published: September 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma.

Methods

Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates.

Results

The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05.

Conclusions

In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.
Tranexamic acid for haemostasis and beyond: does dose matter?
Authors: Lam Tammy , Medcalf Robert L. , Cloud Geoffrey C. , Myles Paul S. , Keragala Charithani B.
Published: September 2023

Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960’s to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin.
Secondary analysis of a randomized trial testing community health educator interventions for diabetes prevention among refugees with depression: effects on nutrition, physical activity and sleep
Authors: Wagner Julie A. , Bermúdez-Millán Angela , Buckley Thomas E. , Buxton Orfeu M. , Feinn Richard S. , Kong Sengly , Kuoch Theanvy , Master Lindsay , Scully Mary F.
Published: September 2023

Background

Refugees have high levels of psychological distress that hamper lifestyle change efforts. We previously reported that community health educator (CHE) diabetes prevention interventions decreased HbA1c and depressive symptoms among Cambodian-American refugees with depression; this paper reports health behavior outcomes of those interventions.

Methods

Participants were aged 35–75, Khmer speaking, at risk for diabetes, and met study criteria for likely depression by either a) antidepressant medication and/or b) prolonged elevated depressive symptoms. Participants were randomized to one of three CHE interventions: 1) lifestyle intervention called Eat, Walk, Sleep (EWS), 2) EWS plus medication therapy management with a pharmacist/CHE team (EWS + MTM), or, 3) social services (SS; control). Physical activity and sleep were measured with 7 days of actigraphy. Nutrition was measured as carbohydrates as reported in a culturally tailored food frequency questionnaire. Assessments were at baseline, end point (12 months), and follow-up (15 months).

Results

The n = 188 participants were 78% female, average age of 55 years, half had a household income < $20,000, and modal education was 7.0 years. Individuals in the two treatment groups that received the EWS intervention significantly increased their brown rice consumption (p < .001, Cohen’s d = 0.76) and their moderate-to-vigorous activity (p = .039, d = 0.32). No intervention changed sleep duration, timing, efficiency or wake after sleep onset. Across groups, individuals who increased brown rice consumption, increased vigorous activity and decreased total sleep time variability showed decreased HbA1c, with small effect sizes.

Conclusions

CHEs may improve nutrition and physical activity in refugees with depression but more intensive interventions may be required to impact sleep. Improvements in all three behaviors appear to be associated with HbA1c lowering

Trial registration

ClinicalTrials.gov identifier NCT02502929.
A case of neonatal sweet syndrome associated with mevalonate kinase deficiency
Authors: Irwin Margaret , Tanawattanacharoen Veeraya K. , Turner Amy , Son Mary Beth F. , Hale Rebecca C. , Platt Craig D. , Putra Juan , Schmidt Birgitta A.R. , Wasserman Mollie G.
Published: September 2023

Background

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS.

Case presentation

Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease.

Conclusions

This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty.
Childhood-onset rheumatoid arthritis at a tertiary hospital in Senegal, West Africa
Authors: Sabounji Mounib M. , Lissimo Hilaire , Deme Amina
Published: September 2023

Background

Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn’t been the subject of a specific study.

Objectives

The aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations.

Methods

We conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ.

Results

A total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9.

Conclusion

In our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease.
Obesity is associated with quality of sperm parameters in men with infertility: a cross-sectional study
Authors: Darand Mina , Salimi Zahra , Ghorbani Moloud , Sadeghi Narges , Babaie Syavash , Hosseinzadeh Mahdieh
Published: September 2023

Background

Previous studies examined the effects of obesity on sperm parameters and reported inconsistent results. Thus, the present study aimed to evaluate the association between obesity and the quality of sperm parameters in infertile men.

Material and methods

The present cross-sectional study evaluated 218 infertile men aged 20–50. To this end, the 168-item food frequency questionnaire (FFQ) was utilized to evaluate dietary intake. The anthropometric and biochemical variables were examined using standard methods. Further, the association between obesity and the quality of sperm parameters was evaluated using the controlled linear regression for potential confounders.

Results

The normal sperm morphology had a significant inverse association with BMI [adjusted β − 0.074, CI (− 0.141 to − 0.008), P = 0.029] and WC [adjusted β − 0.026, CI (− 0.051 to − 0.001), P = 0.038]. Additionally, visceral fat had a marginal inverse association with normal sperm morphology [adjusted β − 0.065, CI (− 0.138 to 0.008), P = 0.079] and non-progressive sperm motility [adjusted β − 0.241, CI (− 0.495 to 0.014), P = 0.063].

Conclusion

Even though the present results indicated that obesity, abdominal obesity, and visceral fat had inverse associations with normal sperm morphology, more mechanism-based studies should be conducted to confirm these findings.
Woman-centered care and associated factors among midwives working in urban health centers and public and private hospitals in Tabriz, Iran: a cross-sectional study
Authors: Mashayekh-Amiri Sepideh , Nourizadeh Roghaiyeh , Mohammad-Alizadeh-Charandabi Sakineh , Vaezi Maryam , Meedya Shahla , Mirghafourvand Mojgan
Published: September 2023

Background

Woman-centered care (WCC) is the cornerstone of the midwifery profession. However, no study has been conducted on WCC provided by Iranian midwives and its associated factors. Thus, this study aimed to determine WCC and factors associated with midwives’ WCC for midwives working in urban health centers and public and private hospitals in Tabriz, Iran.

Methods

This cross-sectional study was the first part (i.e., the quantitative phase) of a sequential explanatory mixed-method study conducted on 575 midwives working in urban health centers and public and private hospitals in Tabriz-Iran from November 2022 to January 2023. The required data was collected by distributing a socio-demographic and job characteristics questionnaire and woman-centered care scale-midwife self-report (WCCS-MSR). To determine the factors associated with WCC, an independent t-test or one-way analysis of variance (ANOVA) was used in bivariate analysis, and a general linear model (GLM) was employed in multivariate analysis to control possible confounding variables.

Results

The statistical population consisted of 575 midwives, with a response rate of 88.2%. According to the GLM, the total mean WCCS-MSR score of single [β (95% CI) 23.02 (7.94 to 38.10)] and married [β (95% CI) 21.28 (6.83 to 35.72)] midwives was significantly higher than that of divorced midwives after adjusting their demographic and job characteristics. Also, the total mean WCCS-MSR score of midwives with sufficient income was significantly higher than those with insufficient income [β (95% CI) 8.94 (0.12 to 17.77). In addition, the total mean WCCS-MSR score of midwives with < 5 years of work experience [β (95% CI) − 7.87 (− 14.79 to − 0.94)], and midwives with official-experimental employment status [β (95% CI) − 17.99 (− 30.95 to − 5.02)], was significantly lower than those with more than 5 years of work experience and contractual employment status.

Conclusions

The findings indicate that marital status, level of income, years of practice, and employment status were significantly related to WCC provided by midwives. Focusing only on the midwifery community is insufficient to ensure the improved quality of WCC. However, arrangements should be made at three levels, including policy-makers, managers, and health care provider (midwives).
Psychological distress and musculoskeletal pain in manual therapists during the second wave of the COVID-19 pandemic in Sweden: a cross-sectional study
Authors: Weiss Nathan , Skillgate Eva , Axén Iben
Published: September 2023

Background

The COVID-19 pandemic had an unprecedented impact on healthcare, and the health of healthcare workers has been subject of much research. However, studies of health-related factors in manual therapists during the COVID-19 pandemic are scarce. Research in this field can provide valuable insights for future crises policy and guidelines, including in regions where the public health response to COVID-19 contrasts with that of most other international jurisdictions. The aim was to describe the prevalence of psychological distress and musculoskeletal pain, and to investigate factors potentially associated with high psychological distress and activity-limiting musculoskeletal pain in clinically active chiropractors and naprapaths during the second wave of the COVID-19 pandemic in Sweden.

Methods

A cross-sectional survey was distributed to a representative sample of Swedish manual therapists, between November 2020 and January 2021. High psychological distress and activity-limiting musculoskeletal pain were investigated regarding associations with residing in a municipality with a high spread of infection, a previous/ongoing SARS-CoV-2 infection, clinical interferences and economic consequences associated with the pandemic. Generalized Linear Models with log link and binomial distribution were used, computing prevalence ratios (PR) with 95% confidence intervals (95% CI).

Results

A total of 762 participants were included, representing 46% of the source population. The prevalence of depressive, anxiety, and stress symptoms was 17%, 7%, and 12%, respectively. Neck (50%), low back (46%), upper back (40%), and shoulders (39%) were the most prevalent musculoskeletal pain areas. Economic consequences due to the pandemic were associated with high psychological distress (PR = 2.30, 95% CI: 1.48–3.53).

Conclusions

During the second wave of the COVID-19 pandemic in Sweden, manual therapists primarily suffered from musculoskeletal pain related to the back and shoulders, while depressive symptoms were the most common symptom of psychological distress. Owners of businesses that suffered economic consequences had a higher prevalence of high psychological distress, which may call for targeted support of this group in future similar contexts. Future longitudinal studies during the pandemic are warranted to assess these associations further.
Causal effect of body mass index and physical activity on the risk of joint sports injuries: Mendelian randomization analysis in the European population
Authors: Bi Wen , Yang Mengyue , Jiang Changqing
Published: September 2023

Background

Observational studies can suggest potential associations between variables but cannot establish a causal effect on their own. This study explored the causal associations between body mass index (BMI), physical activity (PA), and joint sports injuries.

Methods

We conducted two-sample Mendelian randomization (MR) using publicly accessed genome-wide association studies (GWAS) datasets to investigate the causal effects of BMI and PA on joint sports injury risk. The inverse-variance weighted method was believed to be the primary MR analysis. Subsequently, sensitivity, pleiotropy, and heterogeneity analyses were employed to estimate the reliability of the results of the current research.

Results

Genetically predicted increased BMI was causally related to the higher sports injury risk of the ankle–foot (OR 1.23, 95% CI 1.09–1.37, p = 4.20E−04), knee (OR 1.32, 95% CI 1.21–1.43, p = 1.57E−11), and shoulder (OR 1.23, 95% CI 1.08–1.40, p = 1.28E−03). Further, the mentioned effects were validated using another set of GWAS data on BMI. Similar causal linkages were exhibited between increased BMI and the growing risk of sports injuries of the ankle–foot (OR 1.34, 95% CI 1.13–1.60, p = 9.51E−04), knee (OR 1.26, 95% CI 1.09–1.45, p = 1.63E−03), and shoulder (OR 1.35, 95% CI 1.09–1.67, p = 5.66E−03). Additionally, accelerometer-based PA measurement (overall average acceleration) (AccAve) was negatively related to sports injuries of the ankle–foot (OR 0.93, 95% CI 0.87–0.99, p = 0.046) and lumbar spine (OR 0.68, 95% CI 0.51–0.92, p = 0.012). Furthermore, we verified that the effect of AccAve on the risk of injury at the ankle–foot still had statistical significance after adjusting BMI. Results were verified as reliable under all sensitive analyses.

Conclusions

This research determined that a higher BMI could raise the sports injury risk of the ankle–foot, knee, and shoulder, while an overall average acceleration PA could reduce the injury risk of the ankle–foot and lumbar spine. These conclusions contribute to a greater knowledge of the roles of BMI and PA in the mechanism of joint sports injuries and offer several suggestions for patients and clinicians.
Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis
Authors: Cauvet Anne , Decellas Arthur , Guignabert Christophe , Rongvaux-Gaïda Dominique , Thuillet Raphaël , Ottaviani Mina , Tu Ly , Rieger François , Avouac Jérôme , Allanore Yannick
Published: September 2023

Background

Uncontrolled T-cell activation plays a key role in systemic sclerosis (SSc). Arsenic trioxide (ATO) has immunological effects and has demonstrated potential in preclinical SSc models. In this study, we assessed the efficacy of ATO in Fra2 transgenic (Fra2TG) mice, which develop severe vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human SSc-associated pulmonary hypertension, therefore partially resembling to the SSc human disease.

Methods

The efficacy of ATO in Fra2TG mice was evaluated through histological scoring and determination of cell infiltration. Fibrotic changes in the lungs were assessed by measuring collagen content biochemically, using second harmonic generation to measure fibrillar collagen, and imaging via computed tomography. Cardiovascular effects were determined by measuring right ventricular systolic pressure and vessel remodeling. The mechanism of action of ATO was then investigated by analyzing lung cell infiltrates using flow cytometry and bulk RNA with sequencing techniques.

Results

After ATO treatment, the Ashcroft histological score was substantially decreased by 33% in ATO-treated mice compared to control mice. Other investigations of fibrotic markers showed a trend of reduction in various measurements of fibrosis, but the differences did not reach significance. Further cardiovascular investigations revealed convergent findings supporting a beneficial effect of ATO, with reduced right ventricular systolic pressure and medial wall thickness, and a significant decrease in the number of muscularized distal pulmonary arteries in ATO-treated Fra2TG mice compared to untreated Fra2TG mice. Additionally, inflammatory cell infiltration was also markedly reduced in lesioned lungs. A reduction in the frequency of CD4 + and T effector memory cells, and an increase in the percentage of CD4 + T naive cells in the lungs of ATO-treated Fra-2TG mice, was observed when compared to PBS group Fra-2Tg mice. RNA-seq analysis of ATO-treated mouse lungs revealed a downregulation of biological pathways associated with immune activity and inflammation, such as T-cell activation, regulation of leucocyte activation, leucocyte cell–cell adhesion, and regulation of lymphocyte activation.

Conclusions

Our results suggest the clinical relevance of ATO treatment in SSc. Using the Fra2TG mouse model, we observed significant lung histological changes, a trend towards a decrease in various fibrotic makers, and a strong reduction in vascular remodeling. The mechanism of action of ATO appears to involve a marked counteraction of the immune activation characteristic of SSc, particularly T-cell involvement. These findings pave the way for further studies in SSc.
The effects of HIV and systolic blood pressure on mortality risk in rural South Africa, 2010–2019: a data note
Authors: Houle Brian , Clark Samuel J , Kabudula Chodziwadziwa W , Gómez-Olivé F Xavier , Angotti Nicole , Schatz Enid , Tilstra Andrea M , Mojola Sanyu A , Menken Jane
Published: September 2023

Objectives

South Africa is experiencing both HIV and hypertension epidemics. Data were compiled for a study to identify effects of HIV and high systolic blood pressure on mortality risk among people aged 40-plus in a rural South African area experiencing high prevalence of both conditions. We aim to release the replication data set for this study.

Data description

The research data comes from the 2010-11 Ha Nakekela (We Care) population-based survey nested in the Agincourt Health and socio-Demographic Surveillance System (AHDSS) located in the northeast region of South Africa. An age-sex-stratified probability sample was drawn from the AHDSS. The public data set includes information on individual socioeconomic characteristics and measures of HIV status and blood pressure for participants aged 40-plus by 2019. The AHDSS, through its annual surveillance, provided mortality data for nine years subsequent to the survey. These data were converted to person-year observations and linked to the individual-level survey data using participants’ AHDSS census identifier. The data can be used to replicate Houle et al. (2022) — which used discrete-time event history models stratified by sex to assess differential mortality risks according to Ha Nakekela measures of HIV-infection, HIV-1 RNA viral load, and systolic blood pressure.
Metachronous immune-related adverse events involving type 1 diabetes and isolated adrenocorticotropic hormone deficiency associated with pembrolizumab monotherapy for metastatic head and neck cancer: a case report
Authors: Iijima Hiroaki , Sakai Akihiro , Ebisumoto Koji , Yamauchi Mayu , Teramura Takanobu , Yamazaki Aritomo , Inagi Toshihide , Okami Kenji
Published: September 2023

Background

Immune checkpoint inhibitors might cause immune-related adverse events that are still largely unknown.

Case presentation

An 80-year-old Asian female was diagnosed with cervical lymph node metastasis from lip cancer (cT1N0M0) and underwent right cervical neck dissection. Subsequently, she developed right cervical lymph node relapse and lung metastasis. The patient was deemed eligible for pembrolizumab owing to unresectable neck recurrence and pulmonary metastasis. The Combined Positive Score of the submandibular lymph nodes was 100. Pembrolizumab monotherapy was initiated, and complete remission was achieved. She developed diabetic ketoacidosis in the eighth month and was diagnosed with fulminant type 1 diabetes mellitus. Insulin induction was performed. The patient developed adrenal insufficiency after 10 months. These were immune-related adverse events, caused by pembrolizumab. The patient has remained in complete remission, and pembrolizumab therapy was continued.

Conclusions

The study presents the first reported case of type 1 diabetes in a patient with head and neck squamous cell carcinoma treated with pembrolizumab monotherapy, in Japan. Efficient interdepartmental collaboration will promote the management of severe immune-related adverse events and improve the quality of life of patients.
A deep reinforcement learning assisted task offloading and resource allocation approach towards self-driving object detection
Authors: Nie Lili , Wang Huiqiang , Feng Guangsheng , Sun Jiayu , Lv Hongwu , Cui Hang
Published: September 2023

With the development of communication technology and mobile edge computing (MEC), self-driving has received more and more research interests. However, most object detection tasks for self-driving vehicles are still performed at vehicle terminals, which often requires a trade-off between detection accuracy and speed. To achieve efficient object detection without sacrificing accuracy, we propose an end–edge collaboration object detection approach based on Deep Reinforcement Learning (DRL) with a task prioritization mechanism. We use a time utility function to measure the efficiency of object detection task and aim to provide an online approach to maximize the average sum of the time utilities in all slots. Since this is an NP-hard mixed-integer nonlinear programming (MINLP) problem, we propose an online approach for task offloading and resource allocation based on Deep Reinforcement learning and Piecewise Linearization (DRPL). A deep neural network (DNN) is implemented as a flexible solution for learning offloading strategies based on road traffic conditions and wireless network environment, which can significantly reduce computational complexity. In addition, to accelerate DRPL network convergence, DNN outputs are grouped by in-vehicle cameras to form offloading strategies via permutation. Numerical results show that the DRPL scheme is at least 10% more effective and superior in terms of time utility compared to several representative offloading schemes for various vehicle local computing resource scenarios.
Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis
Authors: Wang Min , Feng Jun , Zhou Daixing , Wang Junshuai
Published: September 2023

Background

Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis.

Main findings

LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics.

Conclusions

To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis.

Graphical Abstract
Identification and validation of core genes for type 2 diabetes mellitus by integrated analysis of single-cell and bulk RNA-sequencing
Authors: Yang Tingting , Yan Chaoying , Yang Lan , Tan Jialu , Jiang Shiqiu , Hu Juan , Gao Wei , Wang Qiang , Li Yansong
Published: September 2023

Background

The exact mechanisms of type 2 diabetes mellitus (T2DM) remain largely unknown. We intended to authenticate critical genes linked to T2DM progression by tandem single-cell sequencing and general transcriptome sequencing data.

Methods

T2DM single-cell RNA-sequencing data were submitted by the Gene Expression Omnibus (GEO) database and ArrayExpress (EBI), from which gene expression matrices were retrieved. The common cell clusters and representative marker genes were ascertained by principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), CellMarker, and FindMarkers in two datasets (GSE86469 and GSE81608). T2DM-related differentially expressed marker genes were defined by intersection analysis of marker genes and GSE86468-differentially expressed genes. Receiver operating characteristic (ROC) curves were utilized to assign representative marker genes with diagnostic values by GSE86468, GSE29226 and external validation GSE29221, and their prospective target compounds were forecasted by PubChem. Besides, the R package clusterProfiler-based functional annotation was designed to unveil the intrinsic mechanisms of the target genes. At last, western blot was used to validate the alternation of CDKN1C and DLK1 expression in primary pancreatic islet cells cultured with or without 30mM glucose.

Results

Three common cell clusters were authenticated in two independent T2DM single-cell sequencing data, covering neurons, epithelial cells, and smooth muscle cells. Functional ensemble analysis disclosed an intimate association of these cell clusters with peptide/insulin secretion and pancreatic development. Pseudo-temporal trajectory analysis indicated that almost all epithelial and smooth muscle cells were of neuron origin. We characterized CDKN1C and DLK1, which were notably upregulated in T2DM samples, with satisfactory availability in recognizing three representative marker genes in non-diabetic and T2DM samples, and they were also robustly interlinked with the clinical characteristics of patients. Western blot also demonstrated that, compared with control group, the expression of CDKN1C and DLK1 were increased in primary pancreatic islet cells cultured with 30 mM glucose for 48 h. Additionally, PubChem projected 11 and 21 potential compounds for CDKN1C and DLK1, respectively.

Conclusion

It is desirable that the emergence of the 2 critical genes indicated (CDKN1C and DLK1) could be catalysts for the investigation of the mechanisms of T2DM progression and the exploitation of innovative therapies.
Gut microbiota of old mice worsens neurological outcome after brain ischemia via increased valeric acid and IL-17 in the blood
Authors: Zeng Xianzhang , Li Jun , Shan Weiran , Lai Zhongmeng , Zuo Zhiyi
Published: September 2023

Background

Aging is a significant risk factor for ischemic stroke and worsens its outcome. However, the mechanisms for this worsened neurological outcome with aging are not clearly defined.

Results

Old C57BL/6J male mice (18 to 20 months old) had a poorer neurological outcome and more severe inflammation after transient focal brain ischemia than 8-week-old C57BL/6J male mice (young mice). Young mice with transplantation of old mouse gut microbiota had a worse neurological outcome, poorer survival curve, and more severe inflammation than young mice receiving young mouse gut microbiota transplantation. Old mice and young mice transplanted with old mouse gut microbiota had an increased level of blood valeric acid. Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia. The increase of interleukin-17 caused by valeric acid was inhibited by a free fatty acid receptor 2 antagonist. Neutralizing interleukin-17 in the blood by its antibody improved neurological outcome and attenuated inflammatory response in mice with brain ischemia and receiving valeric acid. Old mice transplanted with young mouse feces had less body weight loss and better survival curve after brain ischemia than old mice transplanted with old mouse feces or old mice without fecal transplantation.

Conclusions

These results suggest that the gut microbiota-valeric acid-interleukin-17 pathway contributes to the aging-related changes in the outcome after focal brain ischemia and response to stimulus. Valeric acid may activate free fatty acid receptor 2 to increase interleukin-17.
Characterization of adolescents with functional respiratory disorders and prior history of SARS-CoV-2
Authors: Bode Sebastian Felix Nepomuk , Schwender Anja , Toth Monika , Kaeppler-Schorn Christine , Siebeneich Ute , Freihorst Joachim , Janda Ales , Fabricius Dorit
Published: September 2023

Background

The SARS-CoV-2 pandemic has caused significant pulmonary morbidity and mortality in the adult population. Children and adolescents typically show milder symptoms; however, a relevant proportion of them report persistent pulmonary symptoms even after mild SARS-CoV-2 infection. Functional respiratory disorders may be relevant differential diagnoses of persistent dyspnea. This study aims at characterizing functional respiratory disorders that may arise after SARS-CoV-2 infection regarding their clinical presentation and pulmonary function tests as well as gaining insights into the clinical course after initiation of appropriate therapy.

Methods

This study retrospectively identified all patients referred to an outpatient clinic for pediatric pulmonology with functional respiratory disorders manifesting after proven SARS-CoV-2 infection between January 1, 2022, and October 31, 2022. Clinical history, thorough clinical examination regarding breathing patterns, and pulmonary function tests (PFTs) were taken into consideration to diagnose functional respiratory disorders.

Results

Twenty-five patients (44% female) with mean (m) age = 12.73 years (SD ± 1.86) who showed distinctive features of functional respiratory disorders after SARS-CoV-2 infection (onset atm = 4.15 (± 4.24) weeks after infection) were identified. Eleven patients showed thoracic dominant breathing with insufficient ventilation, and 4 patients mainly had symptoms of inducible laryngeal obstruction. The rest (n = 10) showed overlap of these two etiologies. Most patients had a flattened inspiratory curve on spirometry and slightly elevated residual volume on body plethysmography, but values of PFTs were normal before and after standardized treadmill exercise testing. Patients were educated about the benign nature of the condition and were offered rebreathing training. All patients with follow-up (n = 5) showed normalization of the breathing pattern within 3 months.

Conclusions

Functional respiratory disorders are important differential diagnoses in persisting post-SARS-CoV-2 dyspnea in adolescents. A combination of clinical history, detailed examination of breathing patterns, and pulmonary function tests are helpful to correctly diagnose these conditions. Reassurance and rebreathing training are the mainstay of the therapy. The clinical course is favorable.
Death in Prison: increasing transparency on next of kin notification and disposition of remains
Authors: Iwai Yoshiko , Behne Michael Forrest , Brinkley-Rubinstein Lauren
Published: September 2023

Background

Policies for next-of-kin (NOK) notification and disposition of remains surrounding death are unclear across the United States’ (US) carceral systems. The goal of this study was to collect data on carceral system policies pertaining to NOK notification and disposition of remains for individuals who are incarcerated. We collected publicly available operational policies for the Federal Bureau of Prisons, Immigration and Customs Enforcement, 50 state prison systems, and the Washington D.C. jail for a total of 53 systems.

Results

Approximately 70% of systems had available policies on NOK notification and disposition of remains. Few systems had information on time constraints for NOK notification, notifying parties or designated contacts person, and ultimate disposition of unclaimed remains. Several systems had no accessible policies.

Conclusions

Across the US, carceral systems vary in policies for notifying NOK after the death of an incarcerated individual and their processes for the disposition of remains. Carceral and health systems should work towards standardization of policies on communication and disposition of remains after death of an individual who is incarcerated to work towards equity.
StudiCare procrastination - Randomized controlled non-inferiority trial of a persuasive design-optimized internet- and mobile-based intervention with digital coach targeting procrastination in college students
Authors: Mutter Agnes , Küchler A.-M. , Idrees A. R. , Kählke F. , Terhorst Y. , Baumeister H.
Published: September 2023

Background

Academic procrastination is widespread among college students. Procrastination is strongly negatively correlated with psychological well-being, thus early interventions are needed. Internet- and mobile-based cognitive behavioral therapy (iCBT) could provide a low-threshold treatment option. Human guidance seems to be a decisive mechanism of change in iCBT. Persuasive design optimization of iCBT and guidance by a digital coach might represent a resource-saving alternative. The study evaluated the non-inferiority of a digital coach in comparison to human guidance with regard to the primary outcome procrastination.

Methods

The iCBT StudiCare procrastination was optimized by principles of the Persuasive System Design (PSD). A total of 233 college students were randomly assigned to either StudiCare procrastination guided by a digital coach (intervention group, IG) or by a human eCoach (control group, CG). All participants were assessed at baseline, 4-, 8- and 12-weeks post-randomization. Symptom change and between-group differences were assessed with latent growth curve models and supported by effect size levels. The non-inferiority margin was set at Cohen’s d = − 0.3.

Results

The primary outcome procrastination measured by the Irrational Procrastination scale (IPS) significantly decreased across groups (γ = − 0.79, p < .001, Cohen’s d = -0.43 to -0.89) from baseline to 12-weeks post-randomization. There were no significant differences between groups (γ = -0.03, p = .84, Cohen’s d = -0.03 to 0.08). Regarding symptoms of depression, no significant time x group effect was found (γ = 0.26, p = .09; Cohen’s d = -0.15 to 0.21). There was also no significant time x group effect on the improvement of symptoms of anxiety (γ = 0.25, p = .09). However, Cohen’s ds were above the non-inferiority margin 8-weeks (Cohen’s d = 0.51) and 12-weeks post-randomization (Cohen’s d = 0.37), preferring the CG. Of the IG, 34% and of the CG, 36% completed 80% of the modules.

Conclusions

The PSD optimized version of StudiCare procrastination is effective in reducing procrastination. The digital coach was not inferior to human guidance. Guidance by a digital coach in iCBT against procrastination for college students could be a resource-saving alternative to human guidance.

Trial registration

The trial was registered at the WHO International Clinical Trials Registry Platform via the German Clinical Trial Register (ID: DRKS00025209, 30/04/2021).
APOE-ε4 and BIN1 increase risk of Alzheimer’s disease pathology but not specifically of Lewy body pathology
Authors: Talyansky Seth , Le Guen Yann , Kasireddy Nandita , Belloy Michael E. , Greicius Michael D.
Published: September 2023

Lewy body (LB) pathology commonly occurs in individuals with Alzheimer’s disease (AD) pathology. However, it remains unclear which genetic risk factors underlie AD pathology, LB pathology, or AD-LB co-pathology. Notably, whether APOE-ε4 affects risk of LB pathology independently from AD pathology is controversial. We adapted criteria from the literature to classify 4,985 subjects from the National Alzheimer’s Coordinating Center (NACC) and the Rush University Medical Center as AD-LB co-pathology (AD+LB+), sole AD pathology (AD+LB–), sole LB pathology (AD–LB+), or no pathology (AD–LB–). We performed a meta-analysis of a genome-wide association study (GWAS) per subpopulation (NACC/Rush) for each disease phenotype compared to the control group (AD–LB–), and compared the AD+LB+ to AD+LB– groups. APOE-ε4 was significantly associated with risk of AD+LB– and AD+LB+ compared to AD–LB–. However, APOE-ε4 was not associated with risk of AD–LB+ compared to AD–LB– or risk of AD+LB+ compared to AD+LB–. Associations at the BIN1 locus exhibited qualitatively similar results. These results suggest that APOE-ε4 is a risk factor for AD pathology, but not for LB pathology when decoupled from AD pathology. The same holds for BIN1 risk variants. These findings, in the largest AD-LB neuropathology GWAS to date, distinguish the genetic risk factors for sole and dual AD-LB pathology phenotypes. Our GWAS meta-analysis summary statistics, derived from phenotypes based on postmortem pathologic evaluation, may provide more accurate disease-specific polygenic risk scores compared to GWAS based on clinical diagnoses, which are likely confounded by undetected dual pathology and clinical misdiagnoses of dementia type.