bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative cultural care training: the impact of flipped classroom methods on critical cultural competencies in psychiatric nursing: a quasi-experimental study
Authors: Sarvarizadeh Mahdiyeh , Miri Sakineh , Darban Fatemeh , Farokhzadian Jamileh
Published: May 2024

Introduction

Healthcare systems are encountering a growing number of diverse and multicultural clients due to globalization and migration. To effectively address the challenges associated with cross-cultural interactions, nurses require a comprehensive framework of critical cultural competencies. One potential approach to enhancing these competencies in mental health care settings is to use innovative methods such as the flipped classroom in cultural care training programs. This study evaluated the effect of using the flipped classroom method in cultural care training on the critical cultural competencies of nurses working in a psychiatric hospital.

Methods

This quasi-experimental study involved 70 nurses working in a psychiatric hospital affiliated with the Kerman University of Medical Sciences in southeastern Iran. Through random sampling, the nurses were allocated into two groups of intervention (n = 35) and control (n = 35). The intervention group participated in a cultural care training program using the flipped classroom method, which consisted of four sessions conducted over a four-week period. To evaluate the nurses’ critical cultural competence, the Almutairi’s Critical Cultural Competence Scale was administered before the training and again one month later.

Results

The study findings indicated no significant differences in the scores of critical cultural competencies between the intervention group (4.53 ± 0.64) and the control group (4.73 ± 0.42) during the pre-test stage (t = 1.53, p = 0.13). Both groups had a similar perception of critical cultural competencies, which was not particularly positive. However, in the posttest stage, the intervention group (5.33 ± 0.49) demonstrated a significant increase in critical cultural competencies compared to the control group (4.75 ± 0.44) (t = 5.14, p = 0.001).

Conclusion

The study results indicated that the use of the flipped classroom method in the cultural care training program effectively enhanced the critical cultural competencies of nurses. Given the importance of cultural care in both physical and psychiatric care settings for multicultural clients, it is crucial for nurses to receive ongoing in-service education that utilizes innovative and active methods such as the flipped classroom.
Physicians’ irrational attitudes on the antibiotic prescribing for the treatment of COVID-19 in Turkey: A multicenter survey
Authors: Polat Yuluğ Demet , Öztürk Berker , Baydar Toprak Oya , Öztürk Ebru , Köktürk Nurdan , Naycı Sibel
Published: May 2024

Background

The inappropriate and excessive use of antibiotics during the coronavirus pandemic has become an important issue.

Objective

Our primary aim is to ascertain the attitudes of physicians toward the antibiotics prescribing for the treatment of COVID-19 in Turkey. Our secondary aim was to identify factors affecting to physicians’ decisions regarding antibiotic therapy for the treatment of COVID-19 and risk factors associated with antibiotic overprescribing.

Methods

It was a multicenter cross-sectional survey. Physicians from 63 different cities were invited to survey through social media (Facebook, Instagram, WhatsApp). Data were collected from respondents through an online questionnaires during November-December 2021.

Results

The survey was completed by 571 participants from 63 cities. Pulmonologists comprised the majority (35.20%), followed by internal medical specialists (27.85%) and general practitioners (23.29%). The rates of participants who started empirical antibiotics in the outpatient, ward, and ICU (intensive care unit) were 70.2%, 85.5%, and 74.6%, respectively. When the practice of prescribing antibiotics by physicians for the treatment of COVID-19 in outpatients was compared according to the healthcare setting (primary, secondary, tertiary care hospitals) no significant difference was found. Sputum purulence (68.2%) was recognized as the most important factor for the decision of antibiotic therapy, followed by procalcitonin levels (64.9%) and abnormal radiological findings (50.3%). The most prescribed antibiotics were respiratory quinolones. (48%, 65.9%, 62.7% outpatient, ward, ICU respectively)

Conclusions

In this study, we found that physicians frequently had irrational attitudes toward antibiotic prescription to COVID-19 patients, including those with minor diseases. Our findings underline that the necessity of particular, workable interventions to guarantee the prudent use of antibiotics in COVID-19.
Pathological and phylogenetic characteristics of fowl AOAV-1 and H5 isolated from naturally infected Meleagris Gallopavo
Authors: Shalaby Shady , Awadin Walaa , Manzoor Rashid , Karam Reham , Mohamadin Mahmoud , Salem Sanaa , El-Shaieb Ahmed
Published: May 2024

Background

In this study, we investigated the prevalence of respiratory viruses in four Hybrid Converter Turkey (Meleagris gallopavo) farms in Egypt. The infected birds displayed severe respiratory signs, accompanied by high mortality rates, suggesting viral infections. Five representative samples from each farm were pooled and tested for H5 & H9 subtypes of avian influenza viruses (AIVs), Avian Orthoavulavirus-1 (AOAV-1), and turkey rhinotracheitis (TRT) using real-time RT-PCR and conventional RT-PCR. Representative tissue samples from positive cases were subjected to histopathology and immunohistochemistry (IHC).

Results

The PCR techniques confirmed the presence of AOAV-1 and H5 AIV genes, while none of the tested samples were positive for H9 or TRT. Microscopic examination of tissue samples revealed congestion and hemorrhage in the lungs, liver, and intestines with leukocytic infiltration. IHC revealed viral antigens in the lungs, liver, and intestines. Phylogenetic analysis revealed that H5 HA belonged to 2.3.4.4b H5 sublineage and AOAV-1 belonged to VII 1.1 genotype.

Conclusions

The study highlights the need for proper monitoring of hybrid converter breeds for viral diseases, and the importance of vaccination programs to prevent unnecessary losses. To our knowledge, this is the first study that reports the isolation of AOAV-1 and H5Nx viruses from Hybrid Converter Turkeys in Egypt.
The effects of dietary Spirulina platensis or curcumin nanoparticles on performance, body chemical composition, blood biochemical, digestive enzyme, antioxidant and immune activities of Oreochromis niloticus fingerlings
Authors: Eissa El-Sayed Hemdan , Khattab Marwa S. , Elbahnaswy Samia , Elshopakey Gehad E. , Alamoudi Muna Omer , Aljàrari Rabab Mohamed , Munir Mohammad B. , Kari Zulhisyam A. , Naiel Mohammed A.E.
Published: May 2024

Context

Recently, prioritize has been given to using natural phytogenic or nano compounds as growth promoters and immunostimulants in fish diets as an alternative to antibiotics.

Aims

The main propose of this trial was to determine the impact of supplementing diets with spirulina or curcumin nanoparticles on the performance and health indicators of Nile tilapia fingerlings.

Methods

In a 56-day feeding trial, 180 tilapia fingerlings were assigned into three main groups, as follows: 1st, control group, 2nd, Spirulina platensis (SP; 5 g kg-1 diet) and 3rd, curcumin nanoparticles (CUR-NPs; 30 mg kg-1 diet).

Key results

Incorporating tilapia diets with SP or CUR-NPs significantly improved performance, body chemical analysis, blood biochemical and hematological indices, digestive enzyme activities, and antioxidant and immunostimulant features compared to the control.

Conclusion

Fortified tilapia diets with CUR-NPs or SP efficiently boost the productivity and health of Nile tilapia fingerlings.

Implications

The research introduces new practical solutions for applying safe feed additives as alternatives to antibiotics in tilapia farming.
Display of porcine epidemic diarrhea virus spike protein B-cell linear epitope on Lactobacillus mucosae G01 S-layer surface induce a robust immunogenicity in mice
Authors: Zhang Bin , Gou Hongchao , Shen Haiyan , Zhang Chunhong , Liu Zhicheng , Wuri Nile , Nie Jingjing , Qu Yunzhi , Zhang Jianfeng , Geri Letu
Published: May 2024

The Porcine epidemic diarrhea virus (PEDV) presents a substantial risk to the domestic pig industry, resulting in extensive and fatal viral diarrhea among piglets. Recognizing the mucosal stimulation triggered by PEDV and harnessing the regulatory impact of lactobacilli on intestinal function, we have developed a lactobacillus-based vaccine that is carefully designed to elicit a strong mucosal immune response. Through bioinformatics analysis, we examined PEDV S proteins to identify B-cell linear epitopes that meet the criteria of being non-toxic, soluble, antigenic, and capable of neutralizing the virus. In this study, a genetically modified strain of Lactobacillus mucosae G01 (L.mucosae G01) was created by utilizing the S layer protein (SLP) as a scaffold for surface presentation. Chimeric immunodominant epitopes with neutralizing activity were incorporated at various sites on SLP. The successful expression of SLP chimeric immunodominant epitope 1 on the surface of L.mucosae G01 was confirmed through indirect immunofluorescence and transmission electron microscopy, revealing the formation of a transparent membrane. The findings demonstrate that the oral administration of L.mucosae G01, which expresses the SLP chimeric immunodominant gene epitope1, induces the production of secreted IgA in the intestine and feces of mice. Additionally, there is an elevation in IgG levels in the serum. Moreover, the levels of cytokines IL-2, IL-4, IFN-γ, and IL-17 are significantly increased compared to the negative control group. These results suggest that L. mucosae G01 has the ability to deliver exogenous antigens and elicit a specific mucosal immune response against PEDV. This investigation presents new possibilities for immunoprophylaxis against PEDV-induced diarrhea.
Considerations for first field trials of low-threshold gene drive for malaria vector control
Authors: Connolly John B. , Burt Austin , Christophides George , Diabate Abdoulaye , Habtewold Tibebu , Hancock Penelope A. , James Anthony A. , Kayondo Jonathan K. , Lwetoijera Dickson Wilson , Manjurano Alphaxard , McKemey Andrew R. , Santos Michael R. , Windbichler Nikolai , Randazzo Filippo
Published: May 2024

Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a ‘causal pathway’ would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems. Specific research questions to be addressed in initial gene drive field trials are identified, and adaptive trial design is explored as a potentially constructive and flexible approach to facilitate testing of the causal pathway. A fundamental question for decision-makers for the first field trials will be whether there should be a selective focus on earlier points of the pathway, such as genetic efficacy via measurement of the increase in frequency and spread of the gene drive system in target populations, or on wider interrogation of the entire pathway including entomological and epidemiological efficacy. How and when epidemiological efficacy will eventually be assessed will be an essential consideration before decisions on any field trial protocols are finalized and implemented, regardless of whether initial field trials focus exclusively on the measurement of genetic efficacy, or on broader aspects of the causal pathway. Statistical and modelling tools are currently under active development and will inform such decisions on initial trial design, locations, and endpoints. Collectively, the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.
The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: recent findings from NHANES 2007–2018
Authors: Tan Mo-Yao , Weng Li , Yang Zhong-Hao , Zhu Si-Xuan , Wu Shan , Su Jun-Hua
Published: May 2024

Objective

This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018.

Methods

This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007–2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further.

Results

The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01–1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants’ sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50.

Conclusions

Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.
Global estimate of burnout among the public health workforce: a systematic review and meta-analysis
Authors: Nagarajan Ramya , Ramachandran Padmavathi , Dilipkumar Rajendran , Kaur Prabhdeep
Published: May 2024

Introduction

Burnout is an occupational phenomenon resulting from chronic workplace stress. We conducted this review to estimate the pooled global prevalence of burnout among the public health workforce.

Methods

We conducted this review as per the PRISMA 2020 guidelines. We included only cross-sectional studies reporting outcome estimates among the study population. We included articles published before December 2023. We used a search strategy to systematically select the articles from PubMed, Embase, and Google Scholar. We assessed the quality of the studies using an adapted version of NIH's study tool assessment for cross-sectional and observational cohort studies. We estimated the pooled proportion using the random-effects model.

Results

We included eight studies in our review, covering a sample size of 215,787. The pooled proportion of burnout was 39% (95% CI: 25–53%; p-value: < 0.001). We also identified high heterogeneity among the included studies in our review (I2: 99.67%; p-value: < 0.001). Seven out of the eight studies were of good quality. The pooled proportion of the studies conducted during the COVID-19 pandemic was 42% (95% CI: 17–66%), whereas for the studies conducted during the non-pandemic period, it was 35% (95% CI: 10–60%).

Conclusion

In our review, more than one-third of public health workers suffer from burnout, which adversely affects individuals' mental and physical health. Burnout among the public health workforce requires attention to improve the well-being of this group. Multisite studies using standardized definitions are needed for appropriate comparisons and a better understanding of variations in burnout in various subgroups based on sociodemographic characteristics and type of work responsibilities. We must design and implement workplace interventions to cope with burnout and increase well-being.

Limitations

Due to the limited research on burnout among public health workers, we could not perform a subgroup analysis on various factors that could have contributed to burnout.
O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology
Authors: Yan Xiaohan , Zheng Jingjing , Ren Wenhao , Li Shaoming , Yang Shuying , Zhi Keqian , Gao Ling
Published: May 2024

O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O‑GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.
Integrated analysis of single-cell and bulk RNA sequencing data reveals a myeloid cell-related regulon predicting neoadjuvant immunotherapy response across cancers
Authors: Liu Hong , Sima Xiaoxian , Xiao Bijing , Gulizeba Haimiti , Zhao Shen , Zhou Ting , Huang Yan
Published: May 2024

Background

Immunotherapy has brought about a paradigm shift in the treatment of cancer. However, the majority of patients exhibit resistance or become refractory to immunotherapy, and the underlying mechanisms remain to be explored.

Methods

Sing-cell RNA sequencing (scRNA‑seq) datasets derived from 1 pretreatment and 1 posttreatment achieving pathological complete response (pCR) patient with lung adenocarcinoma (LUAD) who received neoadjuvant immunotherapy were collected, and pySCENIC was used to find the gene regulatory network (GRN) between cell types and immune checkpoint inhibitor (ICI) response. A regulon predicting ICI response was identified and validated using large‑scale pan-cancer data, including a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 5 ICI transcriptomic cohorts. Symphony reference mapping was performed to construct the myeloid cell map.

Results

Thirteen major cluster cell types were identified by comparing pretreatment and posttreatment patients, and the fraction of myeloid cells was higher in the posttreatment group (19.0% vs. 11.8%). A PPARG regulon (containing 23 target genes) was associated with ICI response, and its function was validated by a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, TCGA pan-cancer cohort, and 5 ICI transcriptomic cohorts. Additionally, a myeloid cell map was developed, and cluster I, II, and III myeloid cells with high expression of PPARG were identified. Moreover, we constructed a website called PPARG (https://pparg.online/PPARG/ or http://43.134.20.130:3838/PPARG/), which provides a powerful discovery tool and resource value for researchers.

Conclusions

The PPARG regulon is a predictor of ICI response. The myeloid cell map enables the identification of PPARG subclusters in public scRNA-seq datasets and provides a powerful discovery tool and resource value.
UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis
Authors: Jiao Kun , Xu Guiqin , Liu Yun , Yang Zhaojuan , Xiang Lvzhu , Chen Zehong , Xu Chen , Zuo You , Wu Zhibai , Zheng Ningqian , Xu Wangjie , Zhang Li , Liu Yongzhong
Published: May 2024

Background

The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis.

Methods

Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1.

Results

UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis.

Conclusions

UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.
Plasma-derived extracellular matrix for xenofree and cost-effective organoid modeling for hepatocellular carcinoma
Authors: El-Derby Azza M. , Khedr Mennatallah A. , Ghoneim Nehal I. , Gabr Mahmoud M. , Khater Sherry M. , El-Badri Nagwa
Published: May 2024

Background

Hepatocellular carcinoma (HCC) causes significant cancer mortality worldwide. Cancer organoids can serve as useful disease models by high costs, complexity, and contamination risks from animal-derived products and extracellular matrix (ECM) that limit its applications. On the other hand, synthetic ECM alternatives also have limitations in mimicking native biocomplexity. This study explores the development of a physiologically relevant HCC organoid model using plasma-derived extracellular matrix as a scaffold and nutritive biomatrix with different cellularity components to better mimic the heterogenous HCC microenvironment. Plasma-rich platelet is recognized for its elevated levels of growth factors, which can promote cell proliferation. By employing it as a biomatrix for organoid culture there is a potential to enhance the quality and functionality of organoid models for diverse applications in biomedical research and regenerative medicine and to better replicate the heterogeneous microenvironment of HCC.

Method

To generate the liver cancer organoids, HUH-7 hepatoma cells were cultured alone (homogenous model) or with human bone marrow-derived mesenchymal stromal cells and human umbilical vein endothelial cells (heterogeneous model) in plasma-rich platelet extracellular matrix (ECM). The organoids were grown for 14 days and analyzed for cancer properties including cell viability, invasion, stemness, and drug resistance.

Results

HCC organoids were developed comprising HUH-7 hepatoma cells with or without human mesenchymal stromal and endothelial cells in plasma ECM scaffolds. Both homogeneous (HUH-7 only) and heterogeneous (mixed cellularity) organoids displayed viability, cancer hallmarks, and chemoresistance. The heterogeneous organoids showed enhanced invasion potential, cancer stem cell populations, and late-stage HCC genetic signatures versus homogeneous counterparts.

Conclusion

The engineered HCC organoids system offers a clinically relevant and cost-effective model to study liver cancer pathogenesis, stromal interactions, and drug resistance. The plasma ECM-based culture technique could enable standardized and reproducible HCC modeling. It could also provide a promising option for organoid culture and scaling up.
Lactate facilitated mitochondrial fission-derived ROS to promote pulmonary fibrosis via ERK/DRP-1 signaling
Authors: Sun Zhiheng , Ji Zhihua , Meng Huiwen , He Wanyu , Li Bin , Pan Xiaoyue , Zhou Yanlin , Yu Guoying
Published: May 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung diseases, which mainly existed in middle-aged and elderly people. The accumulation of reactive oxygen species (ROS) is a common characteristic of IPF. Previous research also shown that lactate levels can be abnormally elevated in IPF patients. Emerging evidence suggested a relationship between lactate and ROS in IPF which needs further elucidation. In this article, we utilized a mouse model of BLM-induced pulmonary fibrosis to detect alterations in ROS levels and other indicators associated with fibrosis. Lactate could induce mitochondrial fragmentation by modulating expression and activity of DRP1 and ERK. Moreover, Increased ROS promoted P65 translocation into nucleus, leading to expression of lung fibrotic markers. Finally, Ulixertinib, Mdivi-1 and Mito-TEMPO, which were inhibitor activity of ERK, DRP1 and mtROS, respectively, could effectively prevented mitochondrial damage and production of ROS and eventually alleviate pulmonary fibrosis. Taken together, these findings suggested that lactate could promote lung fibrosis by increasing mitochondrial fission-derived ROS via ERK/DRP1 signaling, which may provide novel therapeutic solutions for IPF.
The advancement of artificial intelligence in biomedical research and health innovation: challenges and opportunities in emerging economies
Authors: da Silva Renan Gonçalves Leonel
Published: May 2024

The advancement of artificial intelligence (AI), algorithm optimization and high-throughput experiments has enabled scientists to accelerate the discovery of new chemicals and materials with unprecedented efficiency, resilience and precision. Over the recent years, the so-called autonomous experimentation (AE) systems are featured as key AI innovation to enhance and accelerate research and development (R&D). Also known as self-driving laboratories or materials acceleration platforms, AE systems are digital platforms capable of running a large number of experiments autonomously. Those systems are rapidly impacting biomedical research and clinical innovation, in areas such as drug discovery, nanomedicine, precision oncology, and others. As it is expected that AE will impact healthcare innovation from local to global levels, its implications for science and technology in emerging economies should be examined. By examining the increasing relevance of AE in contemporary R&D activities, this article aims to explore the advancement of artificial intelligence in biomedical research and health innovation, highlighting its implications, challenges and opportunities in emerging economies. AE presents an opportunity for stakeholders from emerging economies to co-produce the global knowledge landscape of AI in health. However, asymmetries in R&D capabilities should be acknowledged since emerging economies suffers from inadequacies and discontinuities in resources and funding. The establishment of decentralized AE infrastructures could support stakeholders to overcome local restrictions and opens venues for more culturally diverse, equitable, and trustworthy development of AI in health-related R&D through meaningful partnerships and engagement. Collaborations with innovators from emerging economies could facilitate anticipation of fiscal pressures in science and technology policies, obsolescence of knowledge infrastructures, ethical and regulatory policy lag, and other issues present in the Global South. Also, improving cultural and geographical representativeness of AE contributes to foster the diffusion and acceptance of AI in health-related R&D worldwide. Institutional preparedness is critical and could enable stakeholders to navigate opportunities of AI in biomedical research and health innovation in the coming years.
Massage for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Ruinan , Jin Yaoyu , Jin Zhaokai , Gong Yichen , Chen Lei , Su Hai , Liu Xun
Published: May 2024

Objective

This study aimed to evaluate the effectiveness of massage for postoperative rehabilitation after total knee arthroplasty (TKA).

Data sources

The PubMed, Web of Science, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were systematically searched from inception to May 2024.

Study selection

Any randomized controlled trials on the use of massage for postoperative TKA rehabilitation were included.

Data extraction

A meta-analysis of outcomes, including postoperative pain, knee range of motion (ROM), postoperative D-dimer levels, and length of hospital stay, was performed. The Cochrane Risk of Bias Assessment Tool was used to assess the risk of bias, and the data for each included study were extracted independently by two researchers.

Data synthesis

Eleven randomized controlled clinical trials with 940 subjects were included. The results showed that compared with the control group, the massage group experienced more significant pain relief on the 7th, 14th and 21st days after the operation. Moreover, the improvement in knee ROM was more pronounced on postoperative days 7 and 14. In addition, the massage group reported fewer adverse events. However, there was no statistically significant difference in the reduction in postoperative D-dimer levels between the patients and controls. Subgroup analysis revealed that massage shortened the length of hospital stay for postoperative patients in China but not significantly for patients in other regions. Nevertheless, the heterogeneity of the studies was large.

Conclusions

Increased massage treatment was more effective at alleviating pain and improving knee ROM in early post-TKA patients. However, massage did not perform better in reducing D-dimer levels in patients after TKA. Based on the current evidence, massage can be used as an adjunctive treatment for rehabilitation after TKA.
Natural L-type calcium channels antagonists from Chinese medicine
Authors: Xu Fangfang , Cai Wanna , Liu Bo , Qiu Zhenwen , Zhang Xiaoqi
Published: May 2024

L-type calcium channels (LTCCs), the largest subfamily of voltage-gated calcium channels (VGCCs), are the main channels for Ca2+ influx during extracellular excitation. LTCCs are widely present in excitable cells, especially cardiac and cardiovascular smooth muscle cells, and participate in various Ca2+-dependent processes. LTCCs have been considered as worthy drug target for cardiovascular, neurological and psychological diseases for decades. Natural products from Traditional Chinese medicine (TCM) have shown the potential as new drugs for the treatment of LTCCs related diseases. In this review, the basic structure, function of LTCCs, and the related human diseases caused by structural or functional abnormalities of LTCCs, and the natural LTCCs antagonist and their potential usages were summarized.
Hereditary angioedema in Spain: medical care and patient journey
Authors: Caballero Teresa , Alonso Carmen , Baeza María Luisa , Baynova Krasimira , Cabeza José , Cortés Isabel , Escobar Oblitas Danilo , Guilarte Mar , Joral Alejandro , Jurado Palomo Jesús , Lara Jiménez María Ángeles , Martínez Virto Ana , Medrano Laura , Monte Boquet Emilio , Navarro Montserrat , Pérez Diego , Plá Martí María José , Smith Foltz Sara L. , Suero Coral , Zamora Carolina
Published: May 2024

Background

Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain.

Methods

A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model.

Results

Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged.

Conclusions

The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management.
Barriers to diverse clinical trial participation in Duchenne muscular dystrophy: Engaging Hispanic/Latina caregivers and health professionals
Authors: Crossnohere Norah L. , Campoamor Nicola B. , Camino Eric , Dresnick Erin , Martschenko Daphne Oluwaseun , Rodrigues Viana , Apkon Susan , Hazlett Alexis , Mittur Dhruv , Rodriguez Priscilla E. , Bridges John F. P. , Armstrong Niki
Published: May 2024

Background

Despite the increasing availability of clinical trials in Duchenne muscular dystrophy, racial/ethnic minorities and other populations facing health disparities remain underrepresented in clinical trials evaluating products for Duchenne. We sought to understand the barriers faced by Hispanic/Latino families specifically and underrepresented groups more generally to clinical trial participation in Duchenne.

Methods

We engaged two participant groups: Hispanic/Latino caregivers of children with Duchenne in the US, including Puerto Rico, and health professionals within the broader US Duchenne community. Caregiver interviews explored attitudes towards and experiences with clinical trials, while professional interviews explored barriers to clinical trial participation among socio-demographically underrepresented families (e.g., low income, rural, racial/ethnic minority, etc.). Interviews were analyzed aggregately and using a thematic analysis approach. An advisory group was engaged throughout the course of the study to inform design, conduct, and interpretation of findings generated from interviews.

Results

Thirty interviews were conducted, including with 12 Hispanic/Latina caregivers and 18 professionals. We identified barriers to clinical trial participation at various stages of the enrollment process. In the initial identification of patients, barriers included lack of awareness about trials and clinical trial locations at clinics that were less likely to serve diverse patients. In the prescreening process, barriers included ineligibility, anticipated non-compliance in clinical trial protocols, and language discrimination. In screening, barriers included concerns about characteristics of the trial, as well as mistrust/lack of trust. In consent and recruitment, barriers included lack of timely decision support, logistical factors (distance, time, money), and lack of translated study materials.

Conclusions

Numerous barriers hinder participation in Duchenne clinical trials for Hispanic/Latino families and other populations experiencing health disparities. Addressing these barriers necessitates interventions across multiple stages of the clinical trial enrollment process. Recommendations to enhance participation opportunities include developing clinical trial decision support tools, translating prominent clinical trials educational resources such as ClinicalTrials.gov, fostering trusting family-provider relationships, engaging families in clinical trial design, and establishing ethical guidelines for pre-screening potentially non-compliant patients.
Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes
Authors: Junhasavasdikul Detajin , Kasemchaiyanun Akarawut , Tassaneyasin Tanakorn , Petnak Tananchai , Bezerra Frank Silva , Mellado‐Artigas Ricard , Chen Lu , Sutherasan Yuda , Theerawit Pongdhep , Brochard Laurent ,   MAFAI VENT investigators
Published: May 2024

Background

Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored.

Methods

Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset.

Results

339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT.

Conclusions

The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis.

Trial registration: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.
Biologically informed NeuralODEs for genome-wide regulatory dynamics
Authors: Hossain Intekhab , Fanfani Viola , Fischer Jonas , Quackenbush John , Burkholz Rebekka
Published: May 2024

Background

Gene regulatory network (GRN) models that are formulated as ordinary differential equations (ODEs) can accurately explain temporal gene expression patterns and promise to yield new insights into important cellular processes, disease progression, and intervention design. Learning such gene regulatory ODEs is challenging, since we want to predict the evolution of gene expression in a way that accurately encodes the underlying GRN governing the dynamics and the nonlinear functional relationships between genes. Most widely used ODE estimation methods either impose too many parametric restrictions or are not guided by meaningful biological insights, both of which impede either scalability, explainability, or both.

Results

We developed PHOENIX, a modeling framework based on neural ordinary differential equations (NeuralODEs) and Hill-Langmuir kinetics, that overcomes limitations of other methods by flexibly incorporating prior domain knowledge and biological constraints to promote sparse, biologically interpretable representations of GRN ODEs. We tested the accuracy of PHOENIX in a series of in silico experiments, benchmarking it against several currently used tools. We demonstrated PHOENIX’s flexibility by modeling regulation of oscillating expression profiles obtained from synchronized yeast cells. We also assessed the scalability of PHOENIX by modeling genome-scale GRNs for breast cancer samples ordered in pseudotime and for B cells treated with Rituximab.

Conclusions

PHOENIX uses a combination of user-defined prior knowledge and functional forms from systems biology to encode biological “first principles” as soft constraints on the GRN allowing us to predict subsequent gene expression patterns in a biologically explainable manner.
Conditional knockdown of OsMLH1 to improve plant prime editing systems without disturbing fertility in rice
Authors: Liu Xiaoshuang , Gu Dongfang , Zhang Yiru , Jiang Yingli , Xiao Zhi , Xu Rongfang , Qin Ruiying , Li Juan , Wei Pengcheng
Published: May 2024

Background

High-efficiency prime editing (PE) is desirable for precise genome manipulation. The activity of mammalian PE systems can be largely improved by inhibiting DNA mismatch repair by coexpressing a dominant-negative variant of MLH1. However, this strategy has not been widely used for PE optimization in plants, possibly because of its less conspicuous effects and inconsistent performance at different sites.

Results

We show that direct RNAi knockdown of OsMLH1 in an ePE5c system increases the efficiency of our most recently updated PE tool by 1.30- to 2.11-fold in stably transformed rice cells, resulting in as many as 85.42% homozygous mutants in the T0 generation. The high specificity of ePE5c is revealed by whole-genome sequencing. To overcome the partial sterility induced by OsMLH1 knockdown of ePE5c, a conditional excision system is introduced to remove the RNAi module by Cre-mediated site-specific recombination. Using a simple approach of enriching excision events, we generate 100% RNAi module-free plants in the T0 generation. The increase in efficiency due to OsMLH1 knockdown is maintained in the excised plants, whose fertility is not impaired.

Conclusions

This study provides a safe and reliable plant PE optimization strategy for improving editing efficiency without disturbing plant development via transient MMR inhibition with an excisable RNAi module of MLH1.
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial
Authors: Bhagavan Chiranth , Glue Paul , Evans Will , Reynolds Lisa , Turner Thivya , King Chris , Russell Bruce R. , Morunga Eva , Mills Jessica Lee , Layton Geoff , Menkes David B.
Published: May 2024

Background

Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer.

Methods

Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first.

Discussion

This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness.

Trial registration

Trial registered on Australian New Zealand Clinical Trials Registry.

Registration number: ACTRN12619001334190p.

Date registered: 30/09/2019.

URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true