bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Congenital Heart Surgical and Interventional Cardiology Outcome Data in a Single Database: The Development of a Patient-Centered Collaboration of the European Congenital Heart Surgeons Association (ECHSA) and the Association for European Paediatric and Congenital Cardiology (AEPC)
Authors: Jacobs Jeffrey P , Krasemann Thomas , Herbst Claudia , Tobota Zdzislaw , Maruszewski Bohdan , Fragata Jose , Ebels Tjark , Vida Vladimiro L , Mattila Ilkka , Kansy Andrzej , Asfour Boulos , Hörer Jürgen , Lotto Attilio A , Çiçek M Sertaç , Liuba Petru , Dittrich Sven , Chessa Massimo , Bökenkamp Regina , Sharland Gurleen , Hanséus Katarina , Blom Nico A , Sarris George E
Published: July 2023

The European Congenital Heart Surgeons Association (ECHSA) Congenital Database (CD) is the second largest clinical pediatric and congenital cardiac surgical database in the world and the largest in Europe, where various smaller national or regional databases exist. Despite the dramatic increase in interventional cardiology procedures over recent years, only scattered national or regional databases of such procedures exist in Europe. Most importantly, no congenital cardiac database exists in the world that seamlessly combines both surgical and interventional cardiology data on an international level; therefore, the outcomes of surgical and interventional procedures performed on the same or similar patients cannot easily be tracked, assessed, and analyzed. In order to fill this important gap in our capability to gather and analyze information on our common patients, ECHSA and The Association for European Paediatric and Congenital Cardiology (AEPC) have embarked on a collaborative effort to expand the ECHSA-CD with a new module designed to capture data about interventional cardiology procedures. The purpose of this manuscript is to describe the concept, the structure, and the function of the new AEPC Interventional Cardiology Part of the ECHSA-CD, as well as the potentially valuable synergies provided by the shared interventional and surgical analyses of outcomes of patients. The new AEPC Interventional Cardiology Part of the ECHSA-CD will allow centers to have access to robust surgical and transcatheter outcome data from their own center, as well as robust national and international aggregate outcome data for benchmarking. Each contributing center or department will have access to their own data, as well as aggregate data from the AEPC Interventional Cardiology Part of the ECHSA-CD. The new AEPC Interventional Cardiology Part of the ECHSA-CD will allow cardiology centers to have access to aggregate cardiology data, just as surgical centers already have access to aggregate surgical data. Comparison of surgical and catheter interventional outcomes could potentially strengthen decision processes. A study of the wealth of information collected in the database could potentially also contribute toward improved early and late survival, as well as enhanced quality of life of patients with pediatric and/or congenital heart disease treated with surgery and interventional cardiac catheterization across Europe and the world.
A Case of Usefulness of Auto-Injectable Adrenaline as a Prophylactic Countermeasure Against Bee Sting for Forestry Workers
Authors: Yanagawa Youichi , Muramatsu Ken-ichi , Suzuki Hiromasa
Published: July 2023

Since 2015, the Ministry of Agriculture, Forestry and Fisheries in Japan has put in place regulations for forestry workers with bee or wasp allergies. These regulations allow workers to carry auto-injectable adrenaline when they engage in forestry work. A 48-year-old male worker identified as having a bee allergy was provided with an auto-injectable adrenaline prescription. The worker had experienced bee stings several times but never had an anaphylactic reaction. However, after suffering two bee stings to the head and face region, he developed an anaphylactic condition. He used the auto-injectable adrenaline on himself and was transported to an acute critical care center. The worker received additional injection of adrenaline at the health center for residual symptoms. The worker survived with no adverses outcome. The present study described the usefulness of prescribed auto-injectable adrenaline as a prophylactic countermeasure against bee stings for forestry workers with documented allergies. This framework may be useful for protecting forestry workers around the world.
Clinical Characteristics of 96 Patients Presenting With Hematogenous Spinal Osteomyelitis- a Retrospective Study
Authors: Truumees Eeric , Alexander Jeremiah , Chandler Calvin , Singh Devender , Geck Matthew , Stokes John
Published: July 2023

Study Design: Retrospective study.

Objective

To report clinical characteristics and course of care for patients diagnosed with hematogenous spinal osteomyelitis (HVO).

Methods

Medical records of patients presenting to two tertiary care centers with HVO were reviewed.

Results

96 consecutive patients with HVO were identified. Mean follow-up was 8.9 months. Most infections occurred in the lumbar region (50.0%). Of the cultures taken, MRSA accounted for 9%; MSSA, 26%; Streptococcus species, 12%; other gram-positive bacteria, 23%; gram-negative, 17%; fungal, 2.6%; and 11.5% of cultures returned no growth. 57 patients underwent surgery. Of these, 79% of the patients had undergone a trial of empiric antibiotics (cefepime and vancomycin) of the day prior to surgery. 44% underwent secondary surgeries, typically due to a heavy wound burden of necrotic tissue and pus. Postoperative antibiotics were prescribed to all patients. 51.6% of the patients were prescribed antibiotic therapy >6 months. Overall mortality rate was 3.8%. Major cause of all deaths was septic shock. Post-infection sequelae occurred in 47.4% of patients. The most common sequelae were persistent or new sites of infection, sepsis, and abscess.

Conclusions

Diabetes, hypertension, and renal failure appear to increase the risk of post-infection sequelae and death. While non-operative management was attempted in nearly 47%, ultimately 73% had surgery. This high rate may reflect our population of patients hospitalized in a tertiary care center. Available data suggests that patients presenting with hematogenous osteomyelitis be followed closely as failure of non-operative management, and resulting morbidity, was high.
Occupational Stress and Its Effects on Nurses at a Health Facility in Ho Municipality, Ghana
Authors: Dartey Anita Fafa , Tackie Vivian , Worna Lotse Comfort , Dziwornu Emmanuel , Affrim Derrick , Delanyo Akosua Dabi Rejoice
Published: July 2023

Introduction

The prevalence of occupational stress among nurses varies significantly around the globe. Nursing is often considered a stressful occupation and can have negative effects on the mental, physical, family relationships, and quality of care given to patients. The aim of this study was to explore the experiences, causes, effects, and coping strategies of occupational stress among nurses working at a health facility in Ho Municipality in Ghana.

Methods

The study employed a qualitative research approach with an exploratory design. Data saturation was reached with 18 participants. Purposive sampling was used to select participants, while semistructured interview guide with voice recorders were used in data collection. Data were manually transcribed and analyzed using thematic analysis.

Results

Overall, four main themes and ten subthemes were developed from this study. The main themes were nurses’ perception of occupational stress, sources of occupational stress, effects of occupational stress, and coping strategies adopted to cope with occupational stress. The subthemes were as follows: negative and positive stressful feeling, individual level, hospital level, general body pain and fatigue, mental health problems, ineffective relationships, low work output, diversional therapy, positive work outcomes, and psychological support from others (family and colleagues).

Discussion

There are more negative effects of occupational stress on nurses. However, most of the nurses adopted coping strategies to reduce stress with little or no support from the hospital. More support from the hospital will be required to totally manage occupational stress.

Conclusion

The study findings revealed how stress affects the daily life and work output of nurses. It is crucial to comprehend how work-related stress affects nurses and what aspects of their workplace are the most burdensome.
Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study
Authors: Stewart Simon , Chan Yih-Kai , Playford David , Harris Sarah , Strange Geoffrey A.
Published: July 2023

Background

We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension.

Methods

Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0–39.9, 40.0–49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension.

Results

A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0–39.9 mmHg, 40.0–49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (−2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHgversus≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0–39.9 mmHg, 1.82-fold higher in 40.0–49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001).

Conclusions

New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.
Automated fundus ultrasound image classification based on siamese convolutional neural networks with multi-attention
Authors: Tan Jiachen , Dong Yongquan , Li Junchi
Published: July 2023

Fundus ultrasound image classification is a critical issue in the medical field. Vitreous opacity (VO) and posterior vitreous detachment (PVD) are two common eye diseases, Now, the diagnosis of these two diseases mainly relies on manual identification by doctors. This method has the disadvantages of time-consuming and manual investment, so it is very meaningful to use computer technology to assist doctors in diagnosis. This paper is the first to apply the deep learning model to VO and PVD classification tasks. Convolutional neural network (CNN) is widely used in image classification. Traditional CNN requires a large amount of training data to prevent overfitting, and it is difficult to learn the differences between two kinds of images well. In this paper, we propose an end-to-end siamese convolutional neural network with multi-attention (SVK_MA) for automatic classification of VO and PVD fundus ultrasound images. SVK_MA is a siamese-structure network in which each branch is mainly composed of pretrained VGG16 embedded with multiple attention models. Each image first is normalized, then is sent to SVK_MA to extract features from the normalized images, and finally gets the classification result. Our approach has been validated on the dataset provided by the cooperative hospital. The experimental results show that our approach achieves the accuracy of 0.940, precision of 0.941, recall of 0.940, F1 of 0.939 which are respectively increased by 2.5%, 1.9%, 3.4% and 2.5% compared with the second highest model.
Machine learning for predicting the risk stratification of 1–5 cm gastric gastrointestinal stromal tumors based on CT
Authors: Zhang Cui , Wang Jian , Yang Yang , Dai Bailing , Xu Zhihua , Zhu Fangmei , Yu Huajun
Published: July 2023

Backgroud

To predict the malignancy of 1–5 cm gastric gastrointestinal stromal tumors (GISTs) by machine learning (ML) on CT images using three models - Logistic Regression (LR), Decision Tree (DT) and Gradient Boosting Decision Tree (GBDT).

Methods

231 patients from Center 1 were randomly assigned into the training cohort (n = 161) and the internal validation cohort (n = 70) in a 7:3 ratio. The other 78 patients from Center 2 served as the external test cohort. Scikit-learn software was used to build three classifiers. The performance of the three models were evaluated by sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC). Diagnostic differences between ML models and radiologists were compared in the external test cohort. Important features of LR and GBDT were analyzed and compared.

Results

GBDT outperformed LR and DT with the largest AUC values (0.981 and 0.815) in the training and internal validation cohorts and the greatest accuracy (0.923, 0.833 and 0.844) across all three cohorts. However, LR was found to have the largest AUC value (0.910) in the external test cohort. DT yielded the worst accuracy (0.790 and 0.727) and AUC values (0.803 and 0.700) in both the internal validation cohort and the external test cohort. GBDT and LR performed better than radiologists. Long diameter was demonstrated to be the same and most important CT feature for GBDT and LR.

Conclusions

ML classifiers, especially GBDT and LR with high accuracy and strong robustness, were considered to be promising in risk classification of 1–5 cm gastric GISTs based on CT. Long diameter was found the most important feature for risk stratification.
Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor
Authors: Zhang Hengzhe , Yue Jinfeng , Hou Xiaohui , Lu Hongjun , Bikdeli Arezou , Guo Haipeng , Li Hao , Li Daqing
Published: July 2023

Background

Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition.

Case presentation

A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections.

Conclusions

This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.
Surgical experience of extracorporeal membrane oxygenation for neonates with severe respiratory failure
Authors: Zhang Qi-Liang , Chen Xiu-Hua , Zhou Si-Jia , Cao Hua , Chen Qiang
Published: July 2023

Objective

Extracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. This paper summarizes our operation experience of neonatal ECMO via cannulation of the internal jugular vein and carotid artery.

Methods

The clinical data of 12 neonates with severe respiratory failure who underwent ECMO via the internal jugular vein and carotid artery in our hospital from January 2021 to October 2022 were collected.

Results

All neonates were successfully operated on. The size of arterial intubation was 8 F, and the size of venous intubation was 10 F. The operation time was 29 (22–40) minutes. ECMO was successfully removed in 8 neonates. Surgeons successfully reconstructed the internal jugular vein and carotid artery of these neonates. Arterial blood flow was unobstructed in 5 patients, mild stenosis was present in 2 patients, and moderate stenosis was present in 1 patient. Venous blood flow was unobstructed in 6 patients, mild stenosis was present in 1 patient, and moderate stenosis was present in 1 patient. The complications were as follows: 1 case had poor neck incision healing after ECMO removal. No complications, such as incisional bleeding, incisional infection, catheter-related blood infection, cannulation accidentally pulling away, vascular laceration, thrombosis, cerebral haemorrhage, cerebral infarction, or haemolysis, occurred in any of the patients.

Conclusion

Cannulation of the internal jugular vein and carotid artery can quickly establish effective ECMO access for neonates with severe respiratory failure. Careful, skilled and delicate operation was essential. In addition, during the cannulation process, we should pay special attention to the position of cannulation, firm fixation and strict aseptic operation.
Identification of Immune Infiltration in Odontogenic Keratocyst by Integrated Bioinformatics Analysis
Authors: Zhong Nian-Nian , Li Su-Ran , Man Qi-Wen , Liu Bing
Published: July 2023

Background

Odontogenic keratocyst (OKC) is a relatively common odontogenic lesion characterized by local invasion in the maxillary and mandibular bones. In the pathological tissue slices of OKC, immune cell infiltrations are frequently observed. However, the immune cell profile and the molecular mechanism for immune cell infiltration of OKC are still unclear. We aimed to explore the immune cell profile of OKC and to explore the potential pathogenesis for immune cell infiltration in OKC.

Methods

The microarray dataset GSE38494 including OKC and oral mucosa (OM) samples were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in OKC were analyzed by R software. The hub genes of OKC were performed by protein-protein interaction (PPI) network. The differential immune cell infiltration and the potential relationship between immune cell infiltration and the hub genes were performed by single-sample gene set enrichment analysis (ssGSEA). The expression of COL1A1 and COL1A3 were confirmed by immunofluorescence and immunohistochemistry in 17 OKC and 8 OM samples.

Results

We detected a total of 402 differentially expressed genes (DEGs), of which 247 were upregulated and 155 were downregulated. DEGs were mainly involved in collagen-containing extracellular matrix pathways, external encapsulating structure organization, and extracellular structure organization. We identified ten hub genes, namely FN1, COL1A1, COL3A1, COL1A2, BGN, POSTN, SPARC, FBN1, COL5A1, and COL5A2. A significant difference was observed in the abundances of eight types of infiltrating immune cells between the OM and OKC groups. Both COL1A1 and COL3A1 exhibited a significant positive correlation with natural killer T cells and memory B cells. Simultaneously, they demonstrated a significant negative correlation with CD56dim natural killer cells, neutrophils, immature dendritic cells, and activated dendritic cells. Immunohistochemistry analysis showed that COL1A1 (P = 0.0131) and COL1A3 (P < 0.001) were significantly elevated in OKC compared with OM.

Conclusions

Our findings provide insights into the pathogenesis of OKC and illuminate the immune microenvironment within these lesions. The key genes, including COL1A1 and COL1A3, may significantly impact the biological processes associated with OKC.
Health literacy at work – individual and organizational health literacy, health supporting leadership and employee wellbeing
Authors: Lindert Lara , Choi Kyung-Eun , Pfaff Holger , Zeike Sabrina
Published: July 2023

Background

Against the backdrop of demographic change and the shortage of skilled workers, employees’ psychological wellbeing is of special interest for employers. In previous studies, individual health literacy has already been positively associated with psychological wellbeing. However, in order to improve health literacy, it is essential to take into account both the individual prerequisites and the demands and complexity of the system in which individuals operate. As current studies primarily focus on employees’ individual health literacy and as the concept of organizational health literacy, so far, is mainly used in the context of health care institutions, this study investigates on the impact of organizational health literacy and health supporting leadership on the relationship between individual health literacy and employees’ psychological wellbeing in a big German company based in the financial sector.

Methods

Data of an employee survey that was conducted in a big German company of the financial sector in October 2021 were analyzed by two mediation analyses using the PROCESS macro by Hayes for SPSS. A total of 2555 employees was included in analyses (51.4% male and 48.6% female).

Results

The relationship between individual health literacy and employees’ psychological wellbeing is partially mediated by organizational health literacy, indirect effect ab 0.268 – CI [0.170, 0.378] and by health supporting leadership, indirect effect ab 0.228 – CI [0.137, 0.329].

Conclusion

Study results provide new indications for planning and evaluating the health strategy of companies. Regarding the psychological wellbeing of employees, practitioners and researchers should focus not only on individual health literacy but also on organizational health literacy and health supporting leadership.
The evolution of COVID-19 vaccine hesitancy in Sub-Saharan Africa: evidence from panel survey data
Authors: Wollburg Philip , Markhof Yannick , Kanyanda Shelton , Zezza Alberto
Published: July 2023

Background

COVID-19 vaccination efforts are lagging in Sub-Saharan Africa, as just over 20 percent of the population has been fully vaccinated. COVID-19 vaccine hesitancy is considered important as a prerequisite for widespread vaccine take-up. Here, we study the dynamics of vaccine acceptance, its correlates, and reasons for hesitancy over time, drawing on two years of panel survey data.

Methods

In this observational study, we use multiple rounds of data from national High Frequency Phone Surveys (HFPS) in five countries in East and West Africa (Burkina Faso, Ethiopia, Malawi, Nigeria, and Uganda), covering a period between 2020 and 2022. The surveys are cross-country comparable and draw their samples from nationally representative sampling frames. Based on this data source, the study presents population-weighted means and performs multivariate regression analysis.

Results

COVID-19 vaccine acceptance was high throughout the study period (68% to 98%). However, acceptance levels were lower in 2022 than in 2020 in three countries (Burkina Faso, Malawi, Nigeria), and higher in one country (Uganda). Moreover, individuals are observed to change their stated vaccine attitudes between survey rounds, to a limited extent in some countries (Ethiopia) and more frequently in others (Burkina Faso, Malawi, Nigeria, Uganda). Vaccine hesitancy is higher in richer households, and those residing in urban areas; among women and those better educated. Hesitancy is lower in larger households and among heads of the household. The main reasons for hesitancy are concerns about side effects of the vaccine, its safety and efficacy, as well as assessments of COVID-19 risk, though these reasons fluctuate over time.

Conclusions

Reported COVID-19 vaccine acceptance levels remain far above vaccination rates in the study countries, suggesting that vaccine hesitancy is not the primary obstacle to reaching greater vaccine coverage, which may instead be related to access and delivery barriers as well as supply shortages. Nevertheless, vaccine attitudes appear malleable so that continued efforts are needed to retain high levels of vaccine acceptance.
Community-Engaged Research Ethics Training (CERET): developing accessible and relevant research ethics training for community-based participatory research with people with lived and living experience using illicit drugs and harm reduction workers
Authors: Morgan Jeffrey , Neufeld Scott D. , Holroyd Heather , Ruiz Jean , Taylor Tara , Nolan Seonaid , Glegg Stephanie
Published: July 2023

Background

Community-based participatory research (CBPR) can directly involve non-academic community members in the research process. Existing resources for research ethics training can be inaccessible to team members without an academic background and do not attend to the full spectrum of ethical issues that arise through community-engaged research practices. We detail an approach to capacity building and training in research ethics in the context of CBPR with people who use(d) illicit drugs and harm reduction workers in Vancouver’s Downtown Eastside neighborhood.

Methods

A project team comprised of academic and community experts in CBPR, research ethics, and harm reduction met over five months to develop the Community-Engaged Research Ethics Training (CERET). The group distilled key principles and content from federal research ethics guidelines in Canada, and developed case examples to situate the principles in the context of research with people who use(d) illicit drugs and harm reduction workers. In addition to content related to federal ethics guidelines, the study team integrated additional content related to ethical issues that arise through community-based research, and ethical principles for research in the Downtown Eastside. Workshops were evaluated using a pre-post questionnaire with attendees.

Results

Over the course of six weeks in January–February 2020, we delivered three in-person workshops for twelve attendees, most of whom were onboarding as peer research assistants with a community-based research project. Workshops were structured around key principles of research ethics: respect for persons, concern for welfare, and justice. The discussion-based format we deployed allowed for the bi-directional exchange of information between facilitators and attendees. Evaluation results suggest the CERET approach was effective, and attendees gained confidence and familiarity with workshop content across learning objectives.

Conclusions

The CERET initiative offers an accessible approach to fulfill institutional requirements while building capacity in research ethics for people who use(d) drugs and harm reduction workers. This approach recognizes community members as partners in ethical decision making throughout the research process and is aligned with values of CBPR. Building capacity around intrinsic and extrinsic dimensions of research ethics can prepare all study team members to attend to ethical issues that arise from CBPR.
The effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials
Authors: Li Guang , Feng Hao , Mao Xin-Liang , Deng Yan-Jun , Wang Xiao-Bao , Zhang Qiong , Guo Yan , Xiao Su-Mei
Published: July 2023

Objective

This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs).

Methods

PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR).

Results

Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = − 0.331, 95% CI  − 0.424 to − 0.238, Peffect < 0.001), insulin (SMD = − 0.185, 95% CI  − 0.313 to − 0.056, Peffect = 0.005), HbA1c (SMD = − 0.421, 95% CI  − 0.584 to − 0.258, Peffect < 0.001), and HOMA-IR (SMD = − 0.224, 95% CI  − 0.342 to − 0.105, Peffect < 0.001). Further subgroup analyses showed that the effect was larger in the subgroups of Caucasians, high baseline body mass index (BMI ≥ 30.0 kg/m2), Bifidobacterium and food-type probiotics (Psubgroup < 0.050).

Conclusion

This study supported that probiotics supplementation had favourable effects on glycaemic control in T2DM patients. It may be a promising adjuvant therapy for patients with T2DM.
Motivations for pre-exposure prophylaxis uptake and decline in an HIV-hyperendemic setting: findings from a qualitative implementation study in Lesotho
Authors: Chebet Joy J. , McMahon Shannon A. , Tarumbiswa Tapiwa , Hlalele Hlalele , Maponga Chivimbiso , Mandara Esther , Ernst Kacey , Alaofe Halimatou , Baernighausen Till , Ehiri John E. , Geldsetzer Pascal , Nichter Mark
Published: July 2023

Background

Pre-Exposure Prophylaxis (PrEP) has demonstrated clinical efficacy in preventing HIV infection, yet its uptake remains low. This study, conducted in five PrEP implementing districts in Lesotho, examined factors motivating persons at risk of HIV infection to adopt or reject PrEP when offered freely.

Methods

In-depth interviews were undertaken with stakeholders directly engaged with PrEP policy (n = 5), program implementation (n = 4), and use (current PrEP users = 55, former PrEP users = 36, and PrEP decliners (n = 6)). Focus group discussions (n = 11, 105 total participants) were conducted with health staff directly providing HIV and PrEP services.

Results

Demand for PrEP was reported highest among those at greatest risk for HIV acquisition: those in serodiscordant relationships and/or engaged in sex work. Culturally sensitive PrEP counseling was described as an opportunity to transfer knowledge, build trust, and address user concerns. Conversely, top-down counseling resulted in PrEP distrust and confusion about HIV status. Key motivations for PrEP uptake revolved around sustaining core social relationships, desire for safer conception, and caring for ailing relatives. The decline of PrEP initiation was driven by a combination of individual-level factors (risk perception, perceived side effects, disbelief of the drug’s efficacy and PrEP’s daily pill regimen), societal factors (lack of social support and HIV-related stigma), and structural factors related to PrEP access.

Conclusions

Our findings suggest strategies for effective national PrEP rollout and implementation include: (1) demand creation campaigns which highlight positive aspects of PrEP, while simultaneously addressing apprehensions for uptake; (2) strengthening health provider counseling capacity; and (3) addressing societal and structural HIV-related stigma.
Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis
Authors: Wang Changxin , Shen Jianfei , Zhang Wei , Wang Xiaoyu , Xu Xiaohong , Lu Xianghui , Xu Dongbin , Yao Lan
Published: July 2023

Background

Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis.

Methods

TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay.

Results

IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs.

Conclusion

miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.
Preclinical and clinical activity of DZD1516, a full blood–brain barrier-penetrant, highly selective HER2 inhibitor
Authors: Zhang Jian , McAndrew Nicholas P. , Wang Xiaojia , Du Yiqun , DiCarlo Brian , Wang Mei , Chen Kan , Yu Wenlei , Hu Xichun
Published: July 2023

Background

Patients with HER2-positive metastatic breast cancer (MBC) are at high risk of developing central nervous system (CNS) metastases. A potent and selective HER2 inhibitor with good blood–brain barrier (BBB) penetration is highly desirable.

Methods

The design and structure–activity relationship of DZD1516 was described. The potency and selectivity of DZD1516 were determined by enzymatic and cellular assays. The antitumor activity of DZD1516 monotherapy or in combination with HER2 antibody–drug conjugate was assessed in CNS and subcutaneous xenograft mouse models. A phase 1 first-in-human study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DZD1516 in patients with HER2+ MBC who relapsed from standard of care.

Results

DZD1516 showed good selectivity against HER2 over wild-type EGFR in vitro and potent antitumor activity in vivo. Twenty-three patients were enrolled and received DZD1516 monotherapy treatment across six dose levels (25–300 mg, twice daily). Dose-limiting toxicities were reported at 300 mg, and thus 250 mg was defined as the maximum tolerated dose. The most common adverse events included headache, vomiting, and hemoglobin decreased. No diarrhea or skin rash was observed at ≤ 250 mg. The mean Kp,uu,CSF was 2.1 for DZD1516 and 0.76 for its active metabolite DZ2678. With median seven lines of prior systemic therapy, the best antitumor efficacy in intracranial, extracranial and overall lesions was stable disease.

Conclusions

DZD1516 provides positive proof of concept for an optimal HER2 inhibitor with high BBB penetration and HER2 selectivity. Further clinical evaluation of DZD1516 is warranted, with the RP2D being 250 mg BID.

Clinicaltrials.gov identifier NCT04509596. Registered on August 12, 2020; Chinadrugtrial: CTR20202424 Registered on December 18, 2020.
USP24-dependent stabilization of Runx2 recruits a p300/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation mice
Authors: Li Xingguo , Zhang Jun , Wang Bing , Chen Chao , Zhang Enyu , Lv Zhengpin , He Qicong , Hu Yaoquan , Wang Xuenan , Zhang Fan
Published: July 2023

Background

Intervertebral disc degeneration (IDD) naturally occurs during the aging process. Its occurrence is closely related to chronic inflammation; however, the causal relationship between them is controversial. This study aimed to investigate if inflammation would promote IDD incidence and explore the underlying mechanism.

Methods

A chronic inflammation mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was performed to determine proinflammatory cytokines in serum. Histological staining was used to evaluate the degeneration of IVDs. Immunoblots and RT-qPCR analyses were performed to measure protein and mRNA expression levels. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays were used to determine the assembly of protein complex.

Results

We found that an inflammatory microenvironment activated p38 kinase, which phosphorylated the Runx2 transcription factor at the Ser28 site. The phosphorylated Runx2 (pRunx2) then recruited a deubiquitinase, ubiquitin-specific peptidase 24 (USP24), which stabilized pRunx2 and protected it from ubiquitin-dependent proteasomal degradation. The stabilized pRunx2 recruited histone acetyltransferase p300 and nuclear receptor coactivator 3 (NCOA3) to assemble a complex. This NCOA3-p300-pRunx2 complex then transactivated the expression of 13 ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) genes, thereby promoting the degradation of extracellular matrix (ECM) in intervertebral discs (IVDs) and causing IDD. Administration of either a p38 inhibitor (doramapimod), a NCOA3 inhibitor (bufalin), or a p300 inhibitor (EML425) significantly decreased the expression of the 13 ADAMTS genes and slowed the degeneration of IVDs.

Conclusion

In summary, our results demonstrate that USP24 protects pRunx2 from proteasomal degradation under chronic inflammation conditions, enabling pRunx2 to transactivate ADAMTS genes and degrade ECM. Our findings provide direct evidence that chronic inflammation triggers IDD and offer a therapeutic strategy for retarding IDD in patients with chronic inflammation.
Humans as blood-feeding sources in sylvatic triatomines of Chile unveiled by next-generation sequencing
Authors: San Juan Esteban , Araya-Donoso Raúl , Sierra-Rosales Catalina , Correa Juana P. , Quiroga Nicol , Campos-Soto Ricardo , Solari Aldo , Llewellyn Martin , Bacigalupo Antonella , Botto-Mahan Carezza
Published: July 2023

Background

Triatomines are blood-sucking insects capable of transmitting Trypanosoma cruzi, the parasite that causes Chagas disease in humans. Vectorial transmission entails an infected triatomine feeding on a vertebrate host, release of triatomine infective dejections, and host infection by the entry of parasites through mucous membranes, skin abrasions, or the biting site; therefore, transmission to humans is related to the triatomine–human contact. In this cross-sectional study, we evaluated whether humans were detected in the diet of three sylvatic triatomine species (Mepraia parapatrica, Mepraia spinolai, and Triatoma infestans) present in the semiarid–Mediterranean ecosystem of Chile.

Methods

We used triatomines collected from 32 sites across 1100 km, with an overall T. cruzi infection frequency of 47.1% (N = 4287 total specimens) by conventional PCR or qPCR. First, we amplified the vertebrate cytochrome b gene (cytb) from all DNA samples obtained from triatomine intestinal contents. Then, we sequenced cytb-positive PCR products in pools of 10–20 triatomines each, grouped by site. The filtered sequences were grouped into amplicon sequence variants (ASVs) with a minimum abundance of 100 reads. ASVs were identified by selecting the best BLASTn match against the NCBI nucleotide database.

Results

Overall, 16 mammal (including human), 14 bird, and seven reptile species were identified in the diet of sylvatic triatomines. Humans were part of the diet of all analyzed triatomine species, and it was detected in 19 sites representing 12.19% of the sequences.

Conclusions

Sylvatic triatomine species from Chile feed on a variety of vertebrate species; many of them are detected here for the first time in their diet. Our results highlight that the sylvatic triatomine–human contact is noteworthy. Education must be enforced for local inhabitants, workers, and tourists arriving in endemic areas to avoid or minimize the risk of exposure to Chagas disease vectors.

Graphical Abstract
Gut microbiota signatures and fecal metabolites in postmenopausal women with osteoporosis
Authors: Wang Han , Liu Jing , Wu Zuoxing , Zhao Yangyang , Cao Man , Shi Baohong , Chen Baolong , Chen Ning , Guo Hao , Li Na , Chen Jian , Xu Ren
Published: July 2023

Background

Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS).

Results

We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD.

Conclusions

Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients’ BMD ​​and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women.
Outcomes of total hip and knee arthroplasty in special populations: a synopsis and critical appraisal of systematic reviews
Authors: Challoumas Dimitris , Munn David , Stockdale Henrietta , Ng Nigel , McCormick Michael , Altell Tareq , Joiya Shaheer , Horton James , Jones Bryn
Published: July 2023

Introduction

This study aimed to present and critically appraise the best available evidence investigating associations between some pre-defined patient-related characteristics and perioperative complications or other outcomes in THA and TKA.

Methods

Electronic databases were searched (Medline, EMBASE, Scopus, CENTRAL) for systematic reviews assessing the following pre-defined patient-related characteristics as possible risk factors for worse peri-operative outcomes in THA and TKA: smoking, alcohol excess, rheumatoid arthritis, human immunodeficiency virus infection, hepatitis C virus infection, mental health conditions, and solid organ transplantation. Our primary outcome was periprosthetic joint infection. Results were analysed separately for THA, TKA and THA/TKA (mixed data).

Results

Based on at least two systematic reviews being in agreement, the following patient-related characteristics were associated with increased incidence of complications as follows: a) Smoking for all-cause revision in THA, for periprosthetic joint infection in TKA and THA/TKA; b) alcohol excess for periprosthetic joint infection in THA/TKA; c) human immunodeficiency virus for periprosthetic joint infection in THA/TKA; d) hepatitis C virus for overall complications, periprosthetic joint infection and all-cause revision in THA and THA/TKA, and for overall complications in TKA. Our study found conflicting evidence for a) smoking as a risk factor for periprosthetic joint infection and aseptic loosening in THA; b) human immunodeficiency virus as a risk factor for all-cause revision for THA/TKA; c) hepatitis C virus as a risk factor for periprosthetic joint infection and all-cause revision in TKA. No certainty of evidence was assigned to these results as this was not assessed by the authors of the majority of the included systematic reviews.

Conclusion

We found that smoking, excess alcohol consumption, RA, and infection with HIV and HCV were associated with a higher incidence of periprosthetic joint infection in one or both of THA and TKA or mixed THA/TKA data. All our results should be interpreted and communicated to patients with caution as the quality of the included systematic reviews was generally poor.
The Hypothalamus-pituitary-adrenocortical Response to Critical Illness: A Concept in Need of Revision
Authors: Langouche Lies , Téblick Arno , Gunst Jan , Van den Berghe Greet
Published: July 2023

Based on insights obtained during the past decade, the classical concept of an activated hypothalamus-pituitary-adrenocortical axis in response to critical illness is in need of revision. After a brief central hypothalamus-pituitary-adrenocortical axis activation, the vital maintenance of increased systemic cortisol availability and action in response to critical illness is predominantly driven by peripheral adaptations rather than by an ongoing centrally activated several-fold increased production and secretion of cortisol. Besides the known reduction of cortisol-binding proteins that increases free cortisol, these peripheral responses comprise suppressed cortisol metabolism in liver and kidney, prolonging cortisol half-life, and local alterations in expression of 11βHSD1, glucocorticoid receptor-α (GRα), and FK506 binding protein 5 (FKBP51) that appear to titrate increased GRα action in vital organs and tissues while reducing GRα action in neutrophils, possibly preventing immune-suppressive off-target effects of increased systemic cortisol availability. Peripherally increased cortisol exerts negative feed-back inhibition at the pituitary level impairing processing of pro-opiomelanocortin into ACTH, thereby reducing ACTH-driven cortisol secretion, whereas ongoing central activation results in increased circulating pro-opiomelanocortin. These alterations seem adaptive and beneficial for the host in the short term. However, as a consequence, patients with prolonged critical illness who require intensive care for weeks or longer may develop a form of central adrenal insufficiency. The new findings supersede earlier concepts such as “relative,” as opposed to “absolute,” adrenal insufficiency and generalized systemic glucocorticoid resistance in the critically ill. The findings also question the scientific basis for broad implementation of stress dose hydrocortisone treatment of patients suffering from acute septic shock solely based on assumption of cortisol insufficiency.