bluuebunny/crossref_metadata_2025 huggingface dataset:
Inequality gaps in modern contraceptive use and associated factors among women of reproductive age in Nigeria between 2003 and 2018
Authors: Bolarinwa Obasanjo Afolabi
Published: June 2024

Background

Inequalities in modern contraceptive use among women in low-income countries remain a major public health challenge. Eliminating or reducing the inequalities in modern contraceptive use among women could accelerate the achievement of Sustainable Development Goals, Targets 3.7 & 5.6. Thus, this study examined the inequality gaps in modern contraceptive use and associated factors among women of reproductive age in Nigeria between 2003 and 2018.

Methods

This study employed the World Health Organisation’s Health Equity Assessment Toolkit to analyse the 2003 and 2018 Nigeria Demographic Health Surveys. Modern contraceptive use was aggregated using five equity stratifiers: age, economic status, educational level, place, and region of residence among women of reproductive aged 15 to 49, with a sample size of 5,336 and 29,090 for 2003 and 2018, respectively. Inequality was measured in this study using difference (D), ratio (R), population-attributable risk (PAR), and a population-attributable fraction (PAF).

Results

The study shows an increase in modern contraceptive use among women of reproductive age in Nigeria from 8.25% in 2003 to 12.01% in 2018, with the use being more prominent among women of reproductive age 20–49 and those in the richest economic quintile. In both surveys, women with primary education showed the most upward increase in modern contraceptive use. Women residing in the urban areas also show an upward use of modern contraceptives use. The study further highlights inequality gaps, with age being a substantial factor, while economic status and sub-national regions showed mild to marginal inequality gaps. Finally, the educational level of women of reproductive age in Nigeria significantly shows inequality in modern contraceptive use, with a PAF of 129.11 in 2003 and 65.39 in 2018.

Conclusion

The inequality gap in modern contraceptive use among women of reproductive age in Nigeria between 2003 and 2018 reported in this study includes age, education, wealth quintile, residence, and region-related inequalities. The study highlights the need for policies and programmes that target the groups with low use of modern contraceptives to promote equity in family planning services.
Comprehensive knowledge of mother-to-child HIV/AIDS transmission, prevention, and associated factors among reproductive-age women in East Africa: insights from recent demographic and national health surveys
Authors: Terefe Bewuketu , Jembere Mahlet Moges , Liyew Bikis
Published: June 2024

Background

More than 90% of babies acquire HIV/AIDS through vertical transmission, primarily due to low maternal comprehensive knowledge about Mother-To-Child Transmission (MTCT) of HIV/AIDS and its prevention, which is a cornerstone for eliminating MTCT of HIV/AIDS. However, there are limitations in terms of population data and literature evidence based on recent Demographic and Health Surveys (DHS) reports in East Africa. Therefore, this study aims to assess the comprehensive knowledge and PMTCT of HIV/AIDS among women, as well as the associated factors in East Africa.

Methods

Our data was obtained from the most recent DHS conducted in East African countries between 2011 and 2022. For our research, we included DHS data from ten nations, resulting in a total weighted sample of 133,724 women for our investigation. A generalized linear model (GLM) with a log link and binomial family to directly estimate prevalence ratios (PR) and 95% confidence intervals (CI) for the association between the independent variables, and the outcome variable. Finally, we reported the adjusted prevalence ratios along with their corresponding 95% CIs. Factors with p-values ≤ 0.2 for univariate logistic regression and < 0.05 were considered statistically significant factors of HIV/AIDS knowledge and prevention in the final model.

Results

In this study, 59.41% (95% CI: 59.15–59.67) of respondents had a comprehensive knowledge about MTCT of HIV/AIDS and its prevention among reproductive-age women in East Africa. Being in the older age group, better education level, being from a rich household, employment status, having ANC follow up, institutional delivery, and modern contraception usage were associated with higher prevalence ratios of comprehensive knowledge about MTCT of HIV/AIDS and its prevention. However, being single in marital status, rural women, and traditional contraception utilization were associated with lower ratios of comprehensive knowledge about MTCT of HIV/AIDS and its prevention.

Conclusion

Our findings indicate a significant deficiency in comprehensive knowledge and prevention of HIV/AIDS MTCT among women in East Africa. These results emphasize the need for significant improvements in maternal-related health services. It is crucial to effectively target high-risk populations during interventions, raise awareness about this critical public health issue, and address the catastrophic consequences associated with MTCT. By implementing these measures, we can make substantial progress in reducing the transmission of HIV/AIDS from mother to child and ensuring better health outcomes for both mothers and their children.
vSEMERA: pilot project assessing health profession students’ experiences in an international virtual research program
Authors: Bell Laura , Lemos Eliana , Krimphove Jan , Kaiser Stephanie , Guerra-Giraldez Cristina , Lemos Martin
Published: June 2024

Background

The “Virtual Semester for Medical Research Aachen” (vSEMERA) is an international, interdisciplinary, virtual education program developed for health profession students. The first edition (2021) was hosted by the Medical Faculty of RWTH Aachen University (Germany) in cooperation with Centro Universitário Christus (Brazil) and Universidad Peruana Cayetano Heredia (Peru). The primary aim of the 12-weeks program was to provide students with skills in health science research and prepare them for scientific career paths.

Methods

vSEMERA was built on a virtual learning platform, the “vSEMERA-Campus”, designed to foster students’ learning process and social interactions. Maximum flexibility was offered through synchronous and asynchronous teaching, enabling participants to join via any device from any part of the Globe alongside their regular studies. For the program’s first edition (September - November 2021), health profession students from Germany, Brazil, Peru, Spain, and Italy filled all 30 available spots. Satisfaction, quality of the program and courses offered, as well as perceived learning outcomes, were examined using questionnaires throughout and at the end of the program.

Results

The program received a rating of 4.38 out of 5 stars. While it met most expectations (4.29 out of 5), participants were unable to attend as many courses as intended (2.81 out of 5), mainly due to scheduling conflicts with the home university schedule (46%), internships (23%), and general timing issues (31%). Participants acknowledged considerable improvements in their scientific skills, English language skills, confidence in scientific project management, research career progression, and enthusiasm for a scientific career.

Conclusions

vSEMERA represents a promising example of an online international learning and exchange program using pedagogical and technological elements of virtual collaboration and teaching. In addition to advancing future vSEMERA editions, our results may offer insights for similar projects that address the targeted integration of scientific research education into an international, digital learning environment.
Do the teaching, practice and assessment of clinical communication skills align?
Authors: Dewi Sari Puspa , Wilson Amanda , Duvivier Robbert , Kelly Brian , Gilligan Conor
Published: June 2024

Background

Evidence indicates that communication skills teaching learnt in the classroom are not often readily transferable to the assessment methods that are applied nor to the clinical environment. An observational study was conducted to objectively evaluate students’ communication skills in different learning environments. The study sought to investigate the extent to which the communication skills demonstrated by students in classroom, clinical, and assessment settings align.

Method

A mixed methods study was conducted to observe and evaluate students during the fourth year of a five-year medical program. Participants were videorecorded during structured classroom ‘interactional skills’ sessions, as well as clinical encounters with real patients and an OSCE station calling upon communication skills. The Calgary Cambridge Observational Guides was used to evaluate students at different settings.

Result

This study observed 28 students and findings revealed that while in the classroom students were able to practise a broad range of communication skills, in contrast in the clinical environment, information-gathering and relationship-building with patients became the focus of their encounters with patients. In the OSCEs, limited time and high-pressure scenarios caused the students to rush to complete the task which focussed solely on information-gathering and/or explanation, diminishing opportunity for rapport-building with the patient.

Conclusion

These findings indicate a poor alignment that can develop between the skills practiced across learning environments. Further research is needed to investigate the development and application of students’ skills over the long term to understand supports for and barriers to effective teaching and learning of communication skills in different learning environments.
The influence of psychosocial work environment, personal perceived health and job crafting on nurses’ well-being: a cross-sectional survey study
Authors: Zhang Xin , Zhang Chen , Gou Jiayan , Lee Shih-Yu
Published: June 2024

Background

The World Health Organization urged governments to prioritize the health and work well-being of nursing staff by promoting a positive working environment. A safe and healthy physical and psychosocial work environment is a basic human right for nurses. Job crafting is a necessary skill when facing challenging working conditions.

Objectives

This cross-sectional correlational research based on the Job Demands-Resources Model aimed to explore the correlation between psychosocial work environment and work well-being among nurses working in the intensive care unit (ICU) and determine whether personal perceived health could mediate the relationship and whether job crafting can moderate the mediating effect. The study hypothesized that: 1. The psychosocial work environment would impact nurses' work well-being; 2. Personal perceived health would play a role as a mediator in the relationship between psychosocial work environment and work well‐being; 3. Job crafting would moderate the relationship between personal perceived health and work well‐being.

Methods

A total of 655 registered nurses (RNs) from 7 ICUs in a teaching hospital in Beijing participated in this study. The RNs completed a battery questionnaire measuring their health, psychosocial work environment, well-being, and job crafting. PROCESS macros analysis was used to test mediating and moderating effects.

Results

Personal perceived health mediated the relationship between psychosocial work environment and work well-being (b = 0.012, 95% CI [0.008, 0.016]). The moderated mediated analysis revealed that job crafting moderated perceived health’s impact on work well-being (b = -0.007, 95% CI [− 0.010, − 0.003]).

Conclusion

A better psychosocial work environment with well-designed work organization and job content through job crafting could positively impact nurses’ health and work well-being.
Can performance-based financing improve efficiency of health centers in Ethiopia? A Malmquist Productivity Index analysis
Authors: Adugna Mideksa , Dinsa Girmaye , Khuzwayo Nelisiwe
Published: June 2024

Introduction

The Ethiopian government has introduced several healthcare financing reforms intending to improve efficiency. Piloting implementation of performance-based financing is one of these actions. The purpose of this research is to assess the efficiency of healthcare facilities that have implemented performance-based financing compared to those that have not.

Methods

Efficiency was measured using a nonparametric data envelopment analysis and the Malmquist Productivity Index technique. Total factor productivity change, technical change, and technological change are compared across eight sampled healthcare facilities that are implementing performance-based financing and eight that are not in Ethiopia.

Results

Health facilities implementing performance-based financing have a mean technical efficiency score of 64%, allowing for a potential 36% reduction in inputs without affecting outputs. Their scale efficiency is 88%, indicating a potential 12% increase in total outputs without expanding facilities. In contrast, facilities not implementing performance-based financing have a mean technical efficiency score of 62%, with a potential for 38% input reduction without affecting outputs. Their scale efficiency is 87%, suggesting a potential 13% increase in total outputs without scaling up facilities. Among the 16 healthcare facilities observed, seven experienced a decline in the mean total productivity, while one remained stagnant. The remaining eight facilities witnessed an increase in productivity. The healthcare facilities implementing performance-based financing showed a 1.3% decrease in mean total productivity during the observed period. Among them, five showed an increase and three showed a decrease in the total factor of productivity. The mean total factor of productivity of all healthcare facilities not implementing performance-based financing remained stagnant over the three-year period (2019–2021), with four showing an increase and four showing a decrease in total productivity.

Conclusions

The study concludes that implementing performance-based financing did not improve productivity levels among healthcare facilities over three years. In fact, productivity decreased among the facilities implementing performance-based financing, while those not implementing it remained stagnant. This shows health facilities that implement performance-based financing tend to utilize more resources for similar outputs, contradicting the anticipated efficiency improvement.
Application of the FRAME-IS to a multifaceted implementation strategy
Authors: Schoenthaler Antoinette , De La Calle Franze , De Leon Elaine , Garcia Masiel , Colella Doreen , Nay Jacalyn , Dapkins Isaac
Published: June 2024

Background

Research demonstrates the importance of documenting adaptations to implementation strategies that support integration of evidence-based interventions into practice. While studies have utilized the FRAME-IS [Framework for Reporting Adaptations and Modifications for Implementation Strategies] to collect structured adaptation data, they are limited by a focus on discrete implementation strategies (e.g., training), which do not reflect the complexity of multifaceted strategies like practice facilitation. In this paper, we apply the FRAME-IS to our trial evaluating the effectiveness of PF on implementation fidelity of an evidence-based technology-facilitated team care model for improved hypertension control within a federally qualified health center (FQHC).

Methods

Three data sources are used to document adaptations: (1) implementation committee meeting minutes, (2) narrative reports completed by practice facilitators, and (3) structured notes captured on root cause analysis and Plan-Do-Study-Act worksheets. Text was extracted from the data sources according to the FRAME-IS modules and inputted into a master matrix for content analysis by two authors; a third author conducted member checking and code validation.

Results

We modified the FRAME-IS to include part 2 of module 2 (what is modified) to add greater detail of the modified strategy, and a numbering system to track adaptations across the modules. This resulted in identification of 27 adaptations, of which 88.9% focused on supporting practices in identifying eligible patients and referring them to the intervention. About half (52.9%) of the adaptations were made to modify the context of the PF strategy to include a group-based format, add community health workers to the strategy, and to shift the implementation target to nurses. The adaptations were often widespread (83.9%), affecting all practices within the FQHC. While most adaptations were reactive (84.6%), they resulted from a systematic process of reviewing data captured by multiple sources. All adaptations included the FQHC in the decision-making process.

Conclusion

With modifications, we demonstrate the ability to document our adaptation data across the FRAME-IS modules, attesting to its applicability and value for a range of implementation strategies. Based on our experiences, we recommend refinement of tracking systems to support more nimble and practical documentation of iterative, ongoing, and multifaceted adaptations.

Trial registration

Clinicaltrials.gov NCT03713515, Registration date: October 19, 2018.
Identification of novel biomarkers of acute phase response in chickens challenged with Escherichia coli lipopolysaccharide endotoxin
Authors: Riva Francesca , Eckersall Peter D. , Chadwick Christopher C. , Chadwick Laura C. , McKeegan Dorothy E. F. , Peinado-Izaguerri Jorge , Bruggeman Geert , Hermans David , McLaughlin Mark , Bain Maureen
Published: June 2024

Background

The chicken’s inflammatory response is an essential part of the bird’s response to infection. A single dose of Escherichia coli (E. coli) lipopolysaccharide (LPS) endotoxin can activate the acute phase response (APR) and lead to the production of acute phase proteins (APPs). In this study, the responses of established chicken APPs, Serum amyloid A (SAA) and Alpha-1-acid-glycoprotein (AGP), were compared to two novel APPs, Hemopexin (Hpx) and Extracellular fatty acid binding protein (Ex-FABP), in 15-day old broilers over a time course of 48 h post E.coli LPS challenge. We aimed to investigate and validate their role as biomarkers of an APR. Novel plant extracts, Citrus (CTS) and cucumber (CMB), were used as dietary supplements to investigate their ability to reduce the inflammatory response initiated by the endotoxin.

Results

A significant increase of established (SAA, AGP) and novel (Ex-FABP, Hpx) APPs was detected post E.coli LPS challenge. Extracellular fatty acid binding protein (Ex-FABP) showed a similar early response to SAA post LPS challenge by increasing ~ 20-fold at 12 h post challenge (P < 0.001). Hemopexin (Hpx) showed a later response by increasing ∼5-fold at 24 h post challenge (P < 0.001) with a similar trend to AGP. No differences in APP responses were identified between diets (CTS and CMB) using any of the established or novel biomarkers.

Conclusions

Hpx and Ex-FABP were confirmed as potential biomarkers of APR in broilers when using an E. coli LPS model along with SAA and AGP. However, no clear advantage for using either of dietary supplements to modulate the APR was identified at the dosage used.
Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway
Authors: Zeng Rong , Zhang Dong , Zhang Jintao , Pan Yun , Liu Xiaofei , Qi Qian , Xu Jiawei , Xu Changjuan , Shi Shuochuan , Wang Junfei , Liu Tian , Dong Liang
Published: June 2024

Background

Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma.

Methods

The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor.

Results

Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-β1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression.

Conclusions

Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.
Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT
Authors: Shen Mengling , Guo Li , Zhang Hengyu , Zheng Bingshu , Liu Xinpei , Gu Jingyu , Yang Tao , Sun Chunfeng , Yi Xuan
Published: June 2024

Radiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.

Graphical Abstract
Long non-coding RNA MEG3 knockdown represses airway smooth muscle cells proliferation and migration via sponging miR-143-3p/FGF9 in asthma
Authors: Gu Jiaying , Zhou Dengfeng
Published: June 2024

Background

Asthma is a respiratory disease characterized by airway remodeling. We aimed to find out the role and mechanism of lncRNA MEG3 in asthma.

Methods

We established a cellular model of asthma by inducing human airway smooth muscle cells (HASMCs) with PDGF-BB, and detected levels of lncRNA MEG3, miR-143-3p and FGF9 in HASMCs through qRT-PCR. The functions of lncRNA MEG3 or miR-143-3p on HASMCs were explored by cell transfection. The binding sites of miR-143-3p and FGF9 were subsequently analyzed with bioinformatics software, and validated with dual-luciferase reporter assay. MTT, 5-Ethynyl-2’-deoxyuridine (EdU) assay, and Transwell were used to detect the effects of lncRNA MEG3 or miR-143-3p on proliferation and migration of HASMCs. QRT-PCR and western blot assay were used to evaluate the level of proliferation-related marker PCNA in HASMCs.

Results

The study found that lncRNA MEG3 negatively correlated with miR-143-3p, and miR-143-3p could directly target with FGF9. Silence of lncRNA MEG3 can suppress migration and proliferation of PDGF-BB-induced HASMCs via increasing miR-143-3p. Further mechanistic studies revealed that miR-143-3p negatively regulated FGF9 expression in HASMCs. MiR-143-3p could inhibit PDGF-BB-induced HASMCs migration and proliferation through downregulating FGF9.

Conclusion

LncRNA MEG3 silencing could inhibit the migration and proliferation of HASMCs through regulating miR-143-3p/FGF9 signaling axis. These results imply that lncRNA MEG3 plays a protective role against asthma.
Risk factors of pneumothorax in computed tomography guided lung nodule marking using autologous blood: a retrospective study
Authors: Wu Shaohang , Wu Jianyang , Xiong Junkai , Huang Chengbin , Lin Yiwei , Guan Jun , Xu Jianxin
Published: June 2024

Background

To investigate the risk factors of pneumothorax of using computed tomography (CT) guidance to inject autologous blood to locate isolated lung nodules.

Methods

In the First Hospital of Putian City, 92 cases of single small pulmonary nodules were retrospectively analyzed between November 2019 and March 2023. Before each surgery, autologous blood was injected, and the complications of each case, such as pneumothorax and pulmonary hemorrhage, were recorded. Patient sex, age, position at positioning, and nodule type, size, location, and distance from the visceral pleura were considered. Similarly, the thickness of the chest wall, the depth and duration of the needle-lung contact, the length of the positioning procedure, and complications connected to the patient’s positioning were noted. Logistics single-factor and multi-factor variable analyses were used to identify the risk factors for pneumothorax. The multi-factor logistics analysis was incorporated into the final nomogram prediction model for modeling, and a nomogram was established.

Results

Logistics analysis suggested that the nodule size and the contact depth between the needle and lung tissue were independent risk factors for pneumothorax.

Conclusion

The factors associated with pneumothorax after localization are smaller nodules and deeper contact between the needle and lung tissue.
“Decompression illness” on extracorporeal membrane oxygenation
Authors: Hu Jiannan , zhao Huijing , Bian BingBing , San Renfei , Yang Peng , Jiang Yongpo
Published: June 2024

Background

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for critically ill patients with cardiopulmonary failure. Air in the ECMO circuit is an emergency, a rare but fatal complication.

Case presentation

We introduce a case of a 76-year-old female who suffered from cardiac arrest complicated with severe trauma and was administered veno-arterial extracorporeal membrane oxygenation. In managing the patient with ECMO, air entered the ECMO circuit, which had not come out nor was folded or broken. Although the ECMO flow was quickly re-established, the patient died 6 h after initiating ECMO therapy.

Conclusions

In this case report, the reason for the complication is drainage insufficiency. This phenomenon is similar to decompression sickness. Understanding this complication is very helpful for educating the ECMO team for preventing this rare but devastating complication of fatal decompression sickness in patients on ECMO.
Primary graft dysfunction in heart transplantation: the challenge to survival
Authors: Sicim Hüseyin , Tam Wing Sum Vincy , Tang Paul C.
Published: June 2024

Primary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the initial 24 h following heart transplantation, in the absence of a discernible secondary cause. Given its intricate nature, definitive definition and diagnosis of PGD continues to pose a challenge. The pathophysiology of PGD encompasses numerous underlying mechanisms, some of which remain to be elucidated, including factors like myocardial damage, the release of proinflammatory mediators, and the occurrence of ischemia-reperfusion injury. The dynamic characteristics of both donors and recipients, coupled with the inclination towards marginal lists containing more risk factors, together contribute to the increased incidence of PGD. The augmentation of therapeutic strategies involving mechanical circulatory support accelerates myocardial recovery, thereby significantly contributing to survival. Nonetheless, a universally accepted treatment algorithm for the swift management of this clinical condition, which necessitates immediate intervention upon diagnosis, remains absent. This paper aims to review the existing literature and shed light on how diagnosis, pathophysiology, risk factors, treatment, and perioperative management affect the outcome of PGD.
Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma
Authors: Chang Esther Wei Yin , Tan Ya Hwee , Chan Jason Yongsheng
Published: June 2024

Peripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage strategy. With further understanding of the molecular pathobiology of PTCL, several innovative approaches incorporating immunomodulatory agents, epigenetic therapies, oncogenic kinase inhibitors and immunotherapeutics have come to the forefront. In this review, we provide a comprehensive overview of the progress in developing clinical prognostic indices for PTCL and describe the broad therapeutic landscape, emphasizing novel targetable pathways that have entered early phase clinical studies.
Integrin-linked kinase-frizzled 7 interaction maintains cancer stem cells to drive platinum resistance in ovarian cancer
Authors: Atwani Rula , Nagare Rohit Pravin , Rogers Amber , Prasad Mayuri , Lazar Virginie , Sandusky George , Tong Yan , Pin Fabrizio , Condello Salvatore
Published: June 2024

Background

Platinum-based chemotherapy regimens are a mainstay in the management of ovarian cancer (OC), but emergence of chemoresistance poses a significant clinical challenge. The persistence of ovarian cancer stem cells (OCSCs) at the end of primary treatment contributes to disease recurrence. Here, we hypothesized that the extracellular matrix protects CSCs during chemotherapy and supports their tumorigenic functions by activating integrin-linked kinase (ILK), a key enzyme in drug resistance.

Methods

TCGA datasets and OC models were investigated using an integrated proteomic and gene expression analysis and examined ILK for correlations with chemoresistance pathways and clinical outcomes. Canonical Wnt pathway components, pro-survival signaling, and stemness were examined using OC models. To investigate the role of ILK in the OCSC-phenotype, a novel pharmacological inhibitor of ILK in combination with carboplatin was utilized in vitro and in vivo OC models.

Results

In response to increased fibronectin secretion and integrin β1 clustering, aberrant ILK activation supported the OCSC phenotype, contributing to OC spheroid proliferation and reduced response to platinum treatment. Complexes formed by ILK with the Wnt receptor frizzled 7 (Fzd7) were detected in tumors and correlated with metastatic progression. Moreover, TCGA datasets confirmed that combined expression of ILK and Fzd7 in high grade serous ovarian tumors is correlated with reduced response to chemotherapy and poor patient outcomes. Mechanistically, interaction of ILK with Fzd7 increased the response to Wnt ligands, thereby amplifying the stemness-associated Wnt/β-catenin signaling. Notably, preclinical studies showed that the novel ILK inhibitor compound 22 (cpd-22) alone disrupted ILK interaction with Fzd7 and CSC proliferation as spheroids. Furthermore, when combined with carboplatin, this disruption led to sustained AKT inhibition, apoptotic damage in OCSCs and reduced tumorigenicity in mice.

Conclusions

This “outside-in” signaling mechanism is potentially actionable, and combined targeting of ILK-Fzd7 may lead to new therapeutic approaches to eradicate OCSCs and improve patient outcomes.
Structure–function characterization of two enzymes from novel subfamilies of manganese peroxidases secreted by the lignocellulose-degrading Agaricales fungi Agrocybe pediades and Cyathus striatus
Authors: Sánchez-Ruiz María Isabel , Santillana Elena , Linde Dolores , Romero Antonio , Martínez Angel T. , Ruiz-Dueñas Francisco Javier
Published: June 2024

Background

Manganese peroxidases (MnPs) are, together with lignin peroxidases and versatile peroxidases, key elements of the enzymatic machineries secreted by white-rot fungi to degrade lignin, thus providing access to cellulose and hemicellulose in plant cell walls. A recent genomic analysis of 52 Agaricomycetes species revealed the existence of novel MnP subfamilies differing in the amino-acid residues that constitute the manganese oxidation site. Following this in silico analysis, a comprehensive structure–function study is needed to understand how these enzymes work and contribute to transform the lignin macromolecule.

Results

Two MnPs belonging to the subfamilies recently classified as MnP-DGD and MnP-ESD—referred to as Ape-MnP1 and Cst-MnP1, respectively—were identified as the primary peroxidases secreted by the Agaricales speciesAgrocybe pediadesandCyathus striatuswhen growing on lignocellulosic substrates. Following heterologous expression and in vitro activation, their biochemical characterization confirmed that these enzymes are active MnPs. However, crystal structure and mutagenesis studies revealed manganese coordination spheres different from those expected after their initial classification. Specifically, a glutamine residue (Gln333) in the C-terminal tail of Ape-MnP1 was found to be involved in manganese binding, along with Asp35 and Asp177, while Cst-MnP1 counts only two amino acids (Glu36 and Asp176), instead of three, to function as a MnP. These findings led to the renaming of these subfamilies as MnP-DDQ and MnP-ED and to re-evaluate their evolutionary origin. Both enzymes were also able to directly oxidize lignin-derived phenolic compounds, as seen for other short MnPs. Importantly, size-exclusion chromatography analyses showed that both enzymes cause changes in polymeric lignin in the presence of manganese, suggesting their relevance in lignocellulose transformation.

Conclusions

Understanding the mechanisms used by basidiomycetes to degrade lignin is of particular relevance to comprehend carbon cycle in nature and to design biotechnological tools for the industrial use of plant biomass. Here, we provide the first structure–function characterization of two novel MnP subfamilies present in Agaricales mushrooms, elucidating the main residues involved in catalysis and demonstrating their ability to modify the lignin macromolecule.
Metals profile of milled shrimps and the potential risk associated with their consumption
Authors: Nkansah Marian Asantewah , Adrewie Dominic , Quarm Ida Sandra , Obiri -Yeboah Seth , Dodd Matt
Published: June 2024

The presence of metals in milled shrimps sold on some major markets in Kumasi were investigated to ascertain their levels and the potential health risk they may pose to humans when ingested, due to the level of pollution in the marine environment where these shrimps are obtained from. The samples, which comprised of 30 composites, were analysed using x-ray florescence spectrometry and found to contain Co, Cr, Cu, Fe, K, Mo, Ca, Zn, As, Sr, and Zr with average concentrations of 4.09 mg kg− 1, 5.17 mg kg− 1, 25.14 mg kg− 1, 351.47 mg kg− 1, 9050.74 mg kg− 1, 4.08 mg kg− 1, 21984.48 mg kg− 1, 696.89 mg kg− 1, 8.99 mg kg− 1, 328.54 mg kg− 1, and 9.86 mg kg− 1 respectively. Non-carcinogenic risk indicators analysed suggested a likelihood of health hazard when the milled shrimps are ingested, particularly concerning is the levels of arsenic determined. The arsenic may, however, be in organic form which will make it less of a concern. The levels of the metals could not be linked statistically to the milling process after comparing them to procured controls, which may suggest that these metals may have been picked up in the aquatic environment and/or prior to milling. There is a need, therefore, for action to reduce pollution and remediate the aquatic environment.
The effect of the sense of Community on Depression, Anxiety, and Stress: the mediation role of a balanced time perspective
Authors: Micillo Luigi , Canale Natale , Naddeo Davide , Cellini Nicola , Mioni Giovanna
Published: June 2024

Purpose

Social context and time are two dimensions within which our entire existence is embedded. Therefore, prompting a positive set of attitudes and beliefs towards these elements is fundamental for individuals’ psychological well-being. Currently, there is limited understanding regarding the interplay between the sense of community and time perspective in relation to psychological distress. The present study aims, at investigating the effects that the sense of community and time perspective have on the levels of anxiety, depression, and stress. Particular attention has been dedicated to testing whether the effect of sense of community on anxiety, depression, and stress is mediated by the deviation from a balanced time perspective.

Methods

To accomplish our purposes, we asked 352 participants to complete an online survey and respond to the Depression, Anxiety, Stress Scale (DASS-21), the Zimbardo Time Perspective Inventory (ZTPI), and the Multi-Dimensional Sense of Community Scale (MTSOCS). From these scales, we obtained the scores for anxiety, depression, and stress as well as a general score for the sense of community and the deviation from a balanced time perspective. We computed three General Linear Mediation Models, one for each scale of the DASS-21.

Results

The results showed that the relationship between sense of community and psychological distress was mediated by the deviation from a balanced time perspective extending previous findings and enriching the existing literature on time perspective.

Conclusion

The results described so far could be applied to build a series of interventions aimed at promoting psychological well-being in the general population. Considering our findings, we suggest that individuals’ health could be promoted by both improving their sense of community, which in turn would decrease their levels of stress, and by restructuring their time perspective when it became dysfunctional and unbalanced.
The power of animation: encouraging doctors to access support for psychological wellbeing
Authors: Tooman Tricia R. , Wakeling Judy , Cunningham Kathryn B. , Smith Kathrine Gibson , Walker Kim A. , Cecil Joanne E. , Laidlaw Anita
Published: June 2024

The COVID-19 pandemic has exacerbated already high rates of poor psychological wellbeing in doctors. Many doctors perceive a stigma associated with acknowledging psychological wellbeing concerns, resulting in a reluctance to seek support for those concerns. The aim of this study was to develop a theoretically-informed and evidence-based composite narrative animation (CNA) to encourage doctors to access support for psychological wellbeing, and to evaluate the acceptability of the CNA.

A composite narrative was developed from an evidence-base of interviews with 27 GP participants across Scotland (May–July 2020). The Behaviour Change Wheel was used to identify behaviour change techniques (BCTs) to be embedded within the CNA. The narrative was turned into a script in collaboration with an animation company. A brief animation ‘Jane the GP’ was developed reflecting specific BCTs.

Scottish doctors (n = 83) were asked for their views on acceptability of the CNA concept, and subsequently asked to provide views on the acceptability of the CNA after viewing it. Participants thought the concept of a CNA was novel but may not appeal to all. After viewing the CNA, the widespread view was that it portrayed an authentic experience, could reduce stigma around seeking support for psychological wellbeing, and highlighted formal routes to access such support.

CNAs are a novel and acceptable intervention method for encouraging doctors to access support for psychological wellbeing. The use of a theory driven intervention development framework to create the CNA facilitates the link between theory and practice.
Destinations after higher education non-completion: the role of social background and pre-tertiary vocational qualifications
Authors: Tieben Nicole
Published: June 2024

Prior research has shown that students from lower socio-economic backgrounds are less likely to graduate. We examine if this can be explained by background-specific pathways into higher education. Many students in Germany enter higher education with a vocational qualification and prior vocational qualifications occur more often among students from lower socio-economic backgrounds. We argue that vocational qualifications shift opportunity structures and opportunity costs of students who have to decide between continuing higher education and alternative options. We therefore examine if parental background and vocational qualifications are associated with the destinations after non-completion. We distinguish the destinations “re-entering higher education”, “vocational training” and “skilled employment”. Using the German Educational Panel Study (NEPS starting cohort 6), we apply competing risks models. Our results show that non-completers from higher socio-economic backgrounds are more likely to re-enter higher education than non-completers from lower socio-economic backgrounds. The higher rates of transfer to skilled employment among non-completers from lower backgrounds are mainly due to the fact that they more often hold a vocational qualification and have good chances to enter the skilled labour market without additional educational investments. Our results hence shed some new light on the question how vocational training “diverts” lower background students from higher education.
Corneal injury repair and the potential involvement of ZEB1
Authors: Jin Lin , Zhang Lijun , Yan Chunxiao , Liu Mengxin , Dean Douglas C. , Liu Yongqing
Published: June 2024

The cornea, consisting of three cellular and two non-cellular layers, is the outermost part of the eyeball and frequently injured by external physical, chemical, and microbial insults. The epithelial-to-mesenchymal transition (EMT) plays a crucial role in the repair of corneal injuries. Zinc finger E-box binding homeobox 1 (ZEB1), an important transcription factor involved in EMT, is expressed in the corneal tissues. It regulates cell activities like migration, transformation, and proliferation, and thereby affects tissue inflammation, fibrosis, tumor metastasis, and necrosis by mediating various major signaling pathways, including transforming growth factor (TGF)-β. Dysfunction of ZEB1 would impair corneal tissue repair leading to epithelial healing delay, interstitial fibrosis, neovascularization, and squamous cell metaplasia. Understanding the mechanism underlying ZEB1 regulation of corneal injury repair will help us to formulate a therapeutic approach to enhance corneal injury repair.
Blood pressure and heart failure: focused on treatment
Authors: Chun Kyeong-Hyeon , Kang Seok-Min
Published: June 2024

Heart failure (HF) remains a significant global health burden, and hypertension is known to be the primary contributor to its development. Although aggressive hypertension treatment can prevent heart changes in at-risk patients, determining the optimal blood pressure (BP) targets in cases diagnosed with HF is challenging owing to insufficient evidence. Notably, hypertension is more strongly associated with HF with preserved ejection fraction than with HF with reduced ejection fraction. Patients with acute hypertensive HF exhibit sudden symptoms of acute HF, especially those manifested with severely high BP; however, no specific vasodilator therapy has proven beneficial for this type of acute HF. Since the majority of medications used to treat HF contribute to lowering BP, and BP remains one of the most important hemodynamic markers, targeted BP management is very concerned in treatment strategies. However, no concrete guidelines exist, prompting a trend towards optimizing therapies to within tolerable ranges, rather than setting explicit BP goals. This review discusses the connection between BP and HF, explores its pathophysiology through clinical studies, and addresses its clinical significance and treatment targets.
Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy
Authors: Ziegler Michael G. , Milic Milos , Dimsdale Joel E. , Mills Paul J.
Published: June 2024

Background

Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.

Methods and results

Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.

Conclusions

OSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.

Trial registration

NCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125.