bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial
Authors: Wijewickrema Ananda , Banneheke Hasini , Pathmeswaran Arunasalam , Refai Fathima Wardha , Kauranaratne Malika , Malavige Neelika , Jeewandara Chandima , Ekanayake Mahendra , Samaraweera Dilhar , Thambavita Dhanusha , Galappatthy Priyadarshani
Published: July 2024

Background

Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19.

Trial design and methods

A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups.

Results

Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 − 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000–65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load.

Conclusion

Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms.

Trial registration number

SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021.
The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody
Authors: Maruyama Shuhei , Wada Daiki , Kanayama Shuji , Shimazu Haruka , Miyano Yumiko , Inoue Akira , Kashihara Masami , Okuda Kazuyuki , Saito Fukuki , Nakamori Yasushi , Ishii Kazuyoshi , Kuwagata Yasuyuki
Published: July 2024

Background

The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection.

Methods

This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression.

Results

Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10–20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19–38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding.

Conclusions

Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.
Radiograph-based rheumatoid arthritis diagnosis via convolutional neural network
Authors: Peng Yong , Huang Xianqian , Gan Minzhi , Zhang Keyue , Chen Yong
Published: July 2024

Objectives

Rheumatoid arthritis (RA) is a severe and common autoimmune disease. Conventional diagnostic methods are often subjective, error-prone, and repetitive works. There is an urgent need for a method to detect RA accurately. Therefore, this study aims to develop an automatic diagnostic system based on deep learning for recognizing and staging RA from radiographs to assist physicians in diagnosing RA quickly and accurately.

Methods

We develop a CNN-based fully automated RA diagnostic model, exploring five popular CNN architectures on two clinical applications. The model is trained on a radiograph dataset containing 240 hand radiographs, of which 39 are normal and 201 are RA with five stages. For evaluation, we use 104 hand radiographs, of which 13 are normal and 91 RA with five stages.

Results

The CNN model achieves good performance in RA diagnosis based on hand radiographs. For the RA recognition, all models achieve an AUC above 90% with a sensitivity over 98%. In particular, the AUC of the GoogLeNet-based model is 97.80%, and the sensitivity is 100.0%. For the RA staging, all models achieve over 77% AUC with a sensitivity over 80%. Specifically, the VGG16-based model achieves 83.36% AUC with 92.67% sensitivity.

Conclusion

The presented GoogLeNet-based model and VGG16-based model have the best AUC and sensitivity for RA recognition and staging, respectively. The experimental results demonstrate the feasibility and applicability of CNN in radiograph-based RA diagnosis. Therefore, this model has important clinical significance, especially for resource-limited areas and inexperienced physicians.
Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous
Authors: Lu Jing , Xu Dan , Wan Qianqian , Chen Huijun
Published: July 2024

Background

The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE.

Methods

A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed.

Results

A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012–6.440, P = 0.047).

Conclusion

Active disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.
Accuracy evaluation of dental CBCT and scanned model registration method based on pulp horn mapping surface: an in vitro proof-of-concept
Authors: Wu Dianhao , Jiang Jingang , Wang Jinke , Zhou Shan , Qian Kun
Published: July 2024

Background and aim

3D fusion model of cone-beam computed tomography (CBCT) and oral scanned data can be used for the accurate design of root canal access and guide plates in root canal therapy (RCT). However, the pose accuracy of the dental pulp and crown in data registration has not been investigated, which affects the precise implementation of clinical planning goals. We aimed to establish a novel registration method based on pulp horn mapping surface (PHMSR), to evaluate the accuracy of PHMSR versus traditional methods for crown-pulp registration of CBCT and oral scan data.

Materials and methods

This vitro study collected 8 groups of oral scanned and CBCT data in which the left mandibular teeth were not missing, No. 35 and No. 36 teeth were selected as the target teeth. The CBCT and scanned model were processed to generate equivalent point clouds. For the PHMSR method, the similarity between the feature directions of the pulp horn and the surface normal vectors of the crown were used to determine the mapping points in the CBCT point cloud that have a great influence on the pulp pose. The small surface with adjustable parameters is reconstructed near the mapping point of the crown, and the new matching point pairs between the point and the mapping surface are searched. The sparse iterative closest point (ICP) algorithm is used to solve the new matching point pairs. Then, in the C +  + programming environment with a point cloud library (PCL), the PHMSR, the traditional sparse ICP, ICP, and coherent point drift (CPD) algorithms are used to register the point clouds under two different initial deviations. The root square mean error (RSME) of the crown, crown-pulp orientation deviation (CPOD), and position deviation (CPPD) were calculated to evaluate the registration accuracy. The significance between the groups was tested by a two-tailed paired t-test (p < 0.05).

Results

The crown RSME values of the sparse ICP method (0.257), the ICP method (0.217), and the CPD method (0.209) were not significantly different from the PHMSR method (0.250). The CPOD and CPPD values of the sparse ICP method (4.089 and 0.133), the ICP method (1.787 and 0.700), and the CPD method (1.665 and 0.718) than for the PHMSR method, which suggests that the accuracy of crown-pulp registration is higher with the PHMSR method.

Conclusion

Compared with the traditional method, the PHMSR method has a smaller crown-pulp registration accuracy and a clinically acceptable deviation range, these results support the use of PHMSR method instead of the traditional method for clinical planning of root canal therapy.
Increased pathogenicity and pro-inflammatory capabilities of mucosal-associated invariant T cells involved in Oral Lichen Planus
Authors: Chen Siting , Wu Xiaoli , Yang Yinshen , Xu Xiaoheng , Xiong Xiaoqin , Meng Wenxia
Published: July 2024

Background

Mucosal-associated invariant T (MAIT) cells assume pivotal roles in numerous autoimmune inflammatory maladies. However, scant knowledge exists regarding their involvement in the pathological progression of oral lichen planus (OLP). The focus of our study was to explore whether MAIT cells were altered across distinct clinical types of OLP.

Methods

The frequency, phenotype, and partial functions of MAIT cells were performed by flow cytometry, using peripheral blood from 18 adults with non-erosive OLP and 22 adults with erosive OLP compared with 15 healthy adults. We also studied the changes in MAIT cells in 15 OLP patients receiving and 10 not receiving corticosteroids. Surface proteins including CD4, CD8, CD69, CD103, CD38, HLA-DR, Tim-3, Programmed Death Molecule-1 (PD-1), and related factors released by MAIT cells such as Granzyme B (GzB), interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-17A, and IL-22 were detected.

Results

Within non-erosive OLP patients, MAIT cells manifested an activated phenotype, evident in an elevated frequency of CD69+ CD38+ MAIT cells (p < 0.01). Conversely, erosive OLP patients displayed an activation and depletion phenotype in MAIT cells, typified by elevated CD69 (p < 0.01), CD103 (p < 0.05), and PD-1 expression (p < 0.01). Additionally, MAIT cells exhibited heightened cytokine production, encompassing GzB, IFN-γ, and IL-17A in erosive OLP patients. Notably, the proportion of CD103+ MAIT cells (p < 0.05) and GzB secretion (p < 0.01) by MAIT cells diminished, while the proportion of CD8+ MAIT cells (p < 0.05) rose in OLP patients with corticosteroid therapy.

Conclusions

MAIT cells exhibit increased pathogenicity and pro-inflammatory capabilities in OLP. Corticosteroid therapy influences the expression of certain phenotypes and functions of MAIT cells in the peripheral blood of OLP patients.
Medicinal plants used in multiple sclerosis patients, prevalence and associated factors: a descriptive cross-sectional study
Authors: Nikvarz Naemeh , Sedighi Behnaz , Ansari Mehdi , Shahdizade Shirin , Shojaei Reyhane , Sharififar Fariba
Published: July 2024

Introduction

Multiple sclerosis (MS) is a chronic and debilitating disease that not only leads to disability and associated condition but also impacts one’s ability to maintain a professional life. People’s acceptance and utilization of medicinal plants (MPs) play an important role in managing their treatment process. As a result, this study aims to investigate the use of medicinal herbs among patients with MS.

Methods

A descriptive cross-sectional study was conducted on 150 MS patients who visited a private clinic and the MS Association in Kerman, Iran in 2021. A questionnaire comprising questions about sociodemographic information, disease variables, and aspects of MPs usage was utilized for data collection. Statistical analysis was performed using SPSS version 20 (SPSS Inc., Chicago, IL). The Chi-square test was employed to identify any association between demographic characteristics and MPs usage. To determine the prevalence of plant use in a specific area and the consensus among informants, the use value (UV) and Informant consensus factor (Fic) were calculated.

Results

The study revealed a high prevalence of MPs usage among MS patients. Chamomile (66.6%) and golegavzaban (62.0%) were the most commonly used plants with the highest UV indices (0.88 and 0.82 respectively), while St. John’s wort and licorice were rarely used (0.67% and 4% respectively). Participants cited pursuing a healthier lifestyle as the primary reason for using MPs (24%). St. John’s wort, lavender, and chamomile were the most satisfying plants (100%, 100%, and 53.0% respectively). Chamomile had the highest Fic too. Most patients were motivated to get MPs from their relatives.

Conclusions

Given the widespread use of MPs among MS patients, neurologists should enhance their knowledge in this area to guide patients away from seeking advice from non-professionals. Providing standardized formulations can help prevent potential interactions between MPs and mainstream drugs, thereby improving patients safety and outcomes.
The impact of simulation-based learning on the knowledge, attitude and performance of physiotherapy students on practice placement
Authors: Dairo Yetunde M. , Hunter Kirsty , Ishaku Timothy
Published: July 2024

Background

Practice placement is a crucial part of pre-registration physiotherapy education worldwide. However, educators face challenges in finding practice sites for students to undertake placement. The use of simulation-based (SBL) learning has the potential to replace some traditional placement, thereby increasing placement capacity, but the benefits have not been fully explored. This study aimed to assess the impact of SBL placement on students’ knowledge, attitude, and performance during practice placements with external providers.

Methods

This study utilised an exploratory qualitative research design using a semi-structured interview to collect data from Year 2 students of a 2-year MSc pre-registration physiotherapy programme in the UK. To be eligible to be included in the study, students must have participated in the 4-week simulation placement and have completed all their practice placements with external providers. All the interviews were conducted virtually in a 1:1 setting and recorded. The interviews lasted an average of 45 min. An inductive thematic analysis based on Braun and Clarke’s approach was utilised in this study.

Results

Twelve students consented to participate in this study. The 56 codes generated from the data were categorised into 5 themes; [1] Working together, [2] Working with Service Users, [3] Professionalism, [4] Profession-specific practical skills and [5] Generic practical skills. Participants unanimously expressed a positive view on working in groups, and they believe that engaging with service users who acted as patients enhanced the authenticity of the simulation placement. Subjective and objective assessments were considered important profession-specific skills gained during the simulation. Despite the benefits derived from the simulation placement, some participants felt that the learning experience would have been enriched by periodically changing the groups they were working in and having the opportunity for more 1:1 feedback throughout the four weeks.

Conclusions

SBL has the potential to be a valuable educational experience for physiotherapy students. It may assist in better preparing students for successful integration into the dynamic healthcare environment. To enhance and improve the authenticity of this type of placementour recommendations include recruiting more service users, incorporating and encouraging more intervention-based elements, and increasing the practice educators’ and students’ contact time.
“Expected to happen”: perspectives on post-release overdose from recently incarcerated people with opioid use disorder
Authors: Michener Pryce S. , Bianchet Elyse , Fox Shannon , Evans Elizabeth A. , Friedmann Peter D.
Published: July 2024

Background

Opioid-related overdose is the leading cause of death for people recently released from incarceration, however treatment with medications for opioid use disorder (MOUD) during incarceration can reduce the mortality risk. This study seeks to qualitatively analyze perceptions of post-release overdose risk from the perspectives of people who received MOUD while incarcerated in one of eight Massachusetts jails during 2021–2022 using the Risk Environment Framework to guide analyses.

Methods

N = 38 participants with lived experience of MOUD treatment during incarceration who are now living in the community were interviewed on factors that may contribute to or protect against post-release overdose risk. Themes were identified inductively and deductively using the Risk Environment Framework and its domains, which organizes themes along physical, social, economic, and policy environments on both the micro- and macro- scales.

Results

The physical risk environment included loss of opioid tolerance during incarceration, polysubstance use, and the toxicity of the regional drug supply as key producers of increased risk for post-release overdose. Social drivers of risk included peer group risk norms—including peer-driven harm reduction practices and interpersonal relationships between drug sellers and buyers—as well as macro-level social determinants of health such as housing insecurity and availability of mental health services. Economic drivers of post-release overdose risk included lack of income generation during incarceration and employment challenges. Participants discussed several aspects of policy that contribute to post-release overdose risk, including availability of harm reduction supplies, public health services, and broader policy around MOUD.

Conclusions

The perspectives of people with lived experience are vital to understanding the disproportionate risks of overdose for those recently released from incarceration. Our results highlight the intersectional factors that produce and reproduce the post-release overdose risk environment, providing support for interventions across each domain of the Risk Environment Framework. By capturing perspectives from people with lived experience of OUD and incarceration during this critical period of risk, we can better identify interventions that target and mitigate overdose-related harm in this population.
Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles
Authors: Song Jiahao , Zhou Da , Cui Lili , Wu Chuanjie , Jia Lina , Wang Mengqi , Li Jingrun , Ya Jingyuan , Ji Xunming , Meng Ran
Published: July 2024

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues.

Graphical Abstract
A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery
Authors: Iresjö Britt-Marie , Smedh Ulrika , Engström Cecilia , Persson Jan , Mårtensson Christian , Lundholm Kent
Published: July 2024

Background

Effects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery.

Methods

Patients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen. Arterial blood- and abdominal muscle tissue specimens were collected at start of surgery. Blood chemistry included substrate- and hormone concentrations. Muscle mRNA transcript analyses were performed by microarray and evaluated for changes in gene activities by Gene Ontology algorithms.

Results

Patient groups were comparable in all measured preoperative assessments. The Nutrition Drink had significant metabolic alterations on muscle glucose metabolism (p < 0.05), without any significant effects on amino acid- and protein metabolism. PPN showed similar significant effects on glucose metabolism as Drinks (p < 0.05), but indicated also major positive effects on amino acid- (p < 0.001) and protein anabolism (p < 0.05), particularly by inhibition of muscle protein degradation, related to both ubiquitination of proteins and autophagy/lysosome pathways (p < 0.05).

Conclusion

Conventional overnight preoperative PPN seems effective to induce and support improved muscle protein metabolism in patients aimed at major cancer surgery while preoperative oral carbohydrate loading, according to ERAS-protocols, was ineffective to improve skeletal muscle catabolism and should therefore not be recommended before major cancer surgery.

Trial registration Clinical trials.gov: NCT05080816, Registered June 10th 2021- Retrospectively registered. https://clinicaltrials.gov/study/NCT05080816
Assessment of lifestyle and health-related behaviors and correlates during the COVID-19 pandemic among Lebanese adults
Authors: Saadeh Danielle , Hajj Aline , Malaeb Diana , Sacre Hala , Haddad Chadia , Salameh Pascale
Published: July 2024

Introduction

The novel coronavirus disease 2019 (COVID-19) has quickly become a worldwide threat to human health and has significantly impacted people’s lives and changed their lifestyles and health behaviors. This study aims to assess lifestyle and health-related behaviors (LHBs) and associated factors among the general population in Lebanon during the COVID-19 pandemic.

Methods

An online cross-sectional study was conducted among 403 Lebanese adults. The study questionnaire was developed on Google Forms in English and Arabic. It included self-reported questions about sociodemographic characteristics, COVID-19, and perceived behavioral changes (smoking, alcohol consumption, sexual and hygiene behaviors, and intake of nutritional supplements and immunity-boosting foods). It also comprised three scales, i.e., the Lifestyle and Health Behaviors questionnaire (LHB-17), the WHO-5 Well-being Index, and the Fear of COVID-19 scale (FCV-19S).

Results

The mean age of participants was 29.74 ± 10.81 years, with 51.2% females. Most participants reported that COVID-19 negatively affected their LHBs, mainly diet, sleep, and psychological well-being, while physical activity aspects remained unaffected. Female gender (Unstandardized Beta (ß) =  − 2.336), living in Lebanon (ß = − 7.502), nargileh smoking (ß = − 3.433), high BMI (ß = − 0.263), and increased daily usage of electronic devices during the COVID-19 lockdown (ß = − 0.853) were significantly associated with lower LHB-17 scores, indicating worsened LHB. However, living in urban areas (ß = 2.464), employment status (ß = 1.920), good overall health (ß = 3.543), a higher quality of life (ß = 0.204), and unaffected physical (ß = 2.101) and mental (ß = 1.586) health during the COVID-19 lockdown were all significantly associated with higher LHB-17 scores, reflecting positive LHB.

Conclusion

Lebanese adults reported several unfavorable lifestyle changes and psychological problems during the lockdown due to COVID-19, particularly affecting women, non-workers, waterpipe smokers, electronic device heavy users, people of lower socioeconomic status, and those with chronic diseases. Health promotion strategies are needed to assess negative changes both in physical and mental health and maintain as many positive health-related behaviors as possible among the Lebanese population.
Design of multi-epitope vaccine against porcine rotavirus using computational biology and molecular dynamics simulation approaches
Authors: Zhu Xiaochen , Wang Xinyuan , Liu Tingting , Zhang Dongchao , Jin Tianming
Published: July 2024

Porcine Rotavirus(PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine’s antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.
Novel approach for tracheal resection in Morquio a syndrome with end-stage critical airway obstruction: a UK case series
Authors: Kenth Johnny , Maughan Elizabeth , Butler Colin R , Gabrie Jasleen , Rouhani Maral , Silver Benjamin , Ogunbiyi Olumide K , Wilkinson Stuart , Nandi Reema , Walker Robert , Muthialu Nagarajan , Jones Simon , Hewitt Richard , Bruce Iain A
Published: July 2024

Background

Mucopolysaccharidosis (MPS) type IVA is a rare lysosomal storage disorder caused by aberrations of the N-acetyl-galactosamine-6-sulfatase (GALNS) enzyme. MPS IVA is associated with a wide gamut of respiratory and airway disorders that manifest in a continuum of severity. In individuals exhibiting severe phenotypic expression, terminal stages of the disease frequently culminate in life-threatening, critical airway obstruction. These manifestations of end-stage disease are engendered by an insidious progression of multi-level airway pathologies, comprising of tracheomalacia, stenosis, tortuosity and 'buckling'. Historically, the management of end-stage airway disease has predominantly leaned towards palliative modalities. However, contemporary literature has posited that the potential benefits of tracheal resection with aortopexy, performed under cardiopulmonary bypass (CPB), may offer a promising therapeutic option. In this context, we report on outcomes from patients undergoing a novel approach to tracheal resection that is combined with manubrial resection, leading to improved airway calibre, obviating the requisition for CPB.

Results

In this study, seven patients with severe MPS IVA exhibited clinical symptoms and radiological evidence indicative of advanced airway obstruction. All patients had a tracheal resection with a partial upper manubriectomy via transcervical approach, which did not require CPB. The surgical cohort consisted of 5 females and 2 males, the median age was 16 years (range 11-19) and the median height was 105.6cm (range 96.4-113.4). Postoperatively, significant improvements were seen in forced expiratory volume in 1 second (FEV1), with a mean increase of 0.68 litres (95% CI: 0.45-0.91; SD: 0.20). Notably, other spirometry variables also showed meaningful improvements, providing evidence of positive treatment effects. Furthermore, there were no major long-term complications, and the procedure resulted in a significant enhancement in patient-reported domains using PedsQL (version 4.0).

Conclusions

This study represents the largest case series to date, on tracheal resection in patients with severe MPS IVA. Our findings demonstrate the effectiveness of the transcervical approach with partial manubriectomy for improving respiratory function and quality of life for individuals with advanced airway obstruction. Tracheal resection presents a promising treatment modality for severe cases of MPS IVA. Successful outcomes rely on meticulous multidisciplinary assessment, judicious decision-making, and appropriate timing of tracheal surgery. Further research and long-term follow-up studies are warranted to validate the long-term efficacy and safety of this approach.
Rare disease 101: an online resource teaching on over 7000 rare diseases in one short course
Authors: Dunne Thomas Frederick , Jeffries Daniel , Mckay Lucy
Published: July 2024

Background

An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment. This is well documented in reports published by patient advocacy groups collating the patient experience and has been highlighted by the Department of Health and Social Care in its UK Rare Diseases Framework. One of the four priority areas outlined in this policy published in 2021 is ‘increasing awareness amongst healthcare professionals’.

Medics4RareDiseases (M4RD), a charity based in the UK, has proposed a disease-agnostic approach to educating doctors about rare disease, focusing on the common challenges experienced across this heterogeneous collection of conditions, rather than on the minutiae of each of the > 7000 rare conditions. A literature search using MEDLINE, PubMed Central and Bookshelf confirmed a lack of broad rare disease teaching in medical literature; none of the 10 final resources identified focused on the topic as a whole.

Results

To address this, M4RD created the course ‘Rare Disease 101’. It is accessed online using a learning management system that is free, contains interactive lessons, hosts a discussion board and is easily updated. In the 29 months since going live, 942 individuals have registered with 204 having completed the course; early feedback from 33 respondents was unanimously positive (all participants rated at least good (76%: excellent)) demonstrating that both clinicians and patients can benefit from broad rare disease education. The course is freely available to all at https://learn.m4rd.org/.

Conclusions

Disease-agnostic training about rare disease as a large patient population, focusing on its unique profile of unmet needs, is required. Rare Disease 101 provides a pragmatic approach to an educational challenge that leads to poor patient outcomes. Early results suggest that the educational programme is well-received but further evaluation and assessment is needed.
Glaucoma Rehabilitation using ElectricAI Transcranial Stimulation (GREAT)—study protocol for randomized controlled trial using combined perceptual learning and transcranial electrical stimulation for vision enhancement
Authors: Jia Shuwen , Mei Xiaolin , Chen Lilin , Chan Lok Hin , Tsang Celia , Suen Venus , Li Tingni , Zaw Myo Win , Liu Amanda , Thompson Ben , Sabel Bernhard , Woo George , Leung Christopher K. S. , Yip Shea-ping , Chang Dorita H. F. , Cheong Allen M. Y.
Published: July 2024

Background

Glaucoma patients with irreversible visual field loss often experience decreased quality of life, impaired mobility, and mental health challenges. Perceptual learning (PL) and transcranial electrical stimulation (tES) have emerged as promising interventions for vision rehabilitation, showing potential in restoring residual visual functions. The Glaucoma Rehabilitation using ElectricAI Transcranial stimulation (GREAT) project aims to investigate whether combining PL and tES is more effective than using either method alone in maximizing the visual function of glaucoma patients. Additionally, the study will assess the impact of these interventions on brain neural activity, blood biomarkers, mobility, mental health, quality of life, and fear of falling.

Methods

The study employs a three-arm, double-blind, randomized, superiority-controlled design. Participants are randomly allocated in a 1:1:1 ratio to one of three groups receiving: (1) real PL and real tES, (2) real PL and sham tES, and (3) placebo PL and sham tES. Each participant undergoes 10 sessions per block (~ 1 h each), with a total of three blocks. Assessments are conducted at six time points: baseline, interim 1, interim 2, post-intervention, 1-month post-intervention, and 2-month post-intervention. The primary outcome is the mean deviation of the 24-2 visual field measured by the Humphrey visual field analyzer. Secondary outcomes include detection rate in the suprathreshold visual field, balance and gait functions, and electrophysiological and biological responses. This study also investigates changes in neurotransmitter metabolism, biomarkers, self-perceived quality of life, and psychological status before and after the intervention.

Discussion

The GREAT project is the first study to assess the effectiveness of PL and tES in the rehabilitation of glaucoma. Our findings will offer comprehensive assessments of the impact of these treatments on a wide range of brain and vision-related metrics including visual field, neural activity, biomarkers, mobility, mental health, fear of falling, and quality of life.

Trial registration

ClinicalTrials.gov NCT05874258. Registered on May 15, 2023.
Willingness and capacity of publicly-funded vector control programs in the USA to engage in tick management
Authors: Burtis James C. , Foster Erik , Eisen Rebecca J. , Eisen Lars
Published: July 2024

Background

The vast majority of vector-borne diseases in the USA are associated with mosquitoes or ticks. Mosquito control is often conducted as part of community programs run by publicly-funded entities. By contrast, tick control focuses primarily on individual residential properties and is implemented predominantly by homeowners and the private pest control firms they contract. We surveyed publicly-funded vector control programs (VCPs), presumed to focus mainly on mosquitoes, to determine what tick-related services they currently offer, and their interest in and capacity to expand existing services or provide new ones.

Methods

We distributed a survey to VCPs in the Northeast, Upper Midwest and Pacific Coast states of the USA, where humans are at risk for bites by tick vectors (Ixodes scapularis or Ixodes pacificus) of agents causing Lyme disease and other tick-borne diseases. The data we report are based on responses from 118 VCPs engaged in vector control and with at least some activities focused on ticks.

Results

Despite our survey targeting geographic regions where ticks and tick-borne diseases are persistent and increasing public health concerns, only 11% (12/114) of VCPs reported they took direct action to suppress ticks questing in the environment. The most common tick-related activities conducted by the VCPs were tick bite prevention education for the public (70%; 75/107 VCPs) and tick surveillance (48%; 56/116). When asked which services they would most likely include as part of a comprehensive tick management program, tick bite prevention education (90%; 96/107), tick surveillance (89%; 95/107) and tick suppression guidance for the public (74%; 79/107) were the most common services selected. Most VCPs were also willing to consider engaging in activities to suppress ticks on public lands (68%; 73/107), but few were willing to consider suppressing ticks on privately owned land such as residential properties (15%; 16/107). Across all potential tick-related services, funding was reported as the biggest obstacle to program expansion or development, followed by personnel.

Conclusions

Considering the hesitancy of VCPs to provide tick suppression services on private properties and the high risk for tick bites in peridomestic settings, suppression of ticks on residential properties by private pest control operators will likely play an important role in the tick suppression landscape in the USA for the foreseeable future. Nevertheless, VCPs can assist in this effort by providing locally relevant guidelines to homeowners and private pest control firms regarding best practices for residential tick suppression efforts and associated efficacy evaluations. Publicly-funded VCPs are also well positioned to educate the public on personal tick bite prevention measures and to collect tick surveillance data that provide information on the risk of human encounters with ticks within their jurisdictions.

Graphical Abstract
Exploring methods for creating or adapting knowledge mobilization products for culturally and linguistically diverse audiences: a scoping review
Authors: Elliott Sarah A. , Bialy Liza , Scott Shannon D. , Hartling Lisa
Published: July 2024

Background

Connecting end-users to research evidence has the power to improve patient knowledge and inform health decision-making. Differences in the culture and language of the end users may shape the effectiveness of knowledge mobilization (KMb). This scoping review set out to understand current approaches and methods when creating or adapting KMb products for culturally and linguistically diverse (CALD) audiences.

Methods

We searched 3 databases (Ovid Medline, CINAHL via EBSCOhost, PsychINFO) from 2011 until August 2023. We included any literature about KMb product creation or adaptation processes serving CALD communities. A primary reviewer screened all identified publications and a second reviewer screened publications excluded by the primary. Data were extracted using a standardized form by one reviewer and verified by a second reviewer. Studies were categorized by type of adaptations (‘surface’ and/or ‘deep’ structure) and mapped based on type of stakeholder engagement used in the research approach (i2S model), and end-user involvement (content, design, evaluation and dissemination) in KMb product creation or adaptation.

Results

Ten thousand two hundred ninety-nine unique titles and abstracts were reviewed, 670 full-text studies were retrieved and reviewed, and 78 studies were included in final data extraction and mapping. Twenty-four studies (31%) created or adapted exclusively text-based KMb products such as leaflets and pamphlets and 49 (63%) produced digital products such as videos (n = 16, 33%), mobile applications (n = 14, 29%), and eHealth websites (n = 7, 14%). Twenty-five studies (32%) reported following a framework or theory for their creation or adaptation efforts. Twenty-eight studies (36%) engaged stakeholders in the research approach. Nearly all (96%) involved end-users in creating or adapting the KMb products through involvement in content development (n = 64), design features (n = 52), evaluation (n = 44) and dissemination (n = 20). Thirty-two (41%) studies included reflections from the research teams on the processes for creating or adapting KMb products for CALD communities.

Conclusion

Included studies cited a variety of methods to create or adapt KMb products for CALD communities. Successful uptake of created or adapted KMb products was often the result of collaboration and involvement with end-users for more applicable, accessible and meaningful products. Further research developing guidance and best practices is needed to support the creation or adaptation of KMb products with CALD communities.

Registration

Protocol submitted to Open Science Framework on August 16, 2022 (https://osf.io/9jcw4/).
Meta-analysis of the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction
Authors: Huang Yaqin , Huang Zhoulu , Ou Yi , Yin Lin , Sun Yuxiao , Zong Huiyan
Published: July 2024

Objectives

To systematically evaluate the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction (PFD).

Methods

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was applied. A computer-based retrieval was performed in the databases of PubMed, Web of Science, Embase, and Cochrane Library from database establishment to September 15, 2023, to identify randomized controlled trials on electrical stimulation combined with pelvic floor muscle function exercise on female PFD. Literature screening, data extraction, and quality evaluation were performed independently by two researchers, and meta-analysis was performed using the statistical software Stata15.0.

Results

1. In total, 12 randomized controlled trials were included, involving 721 female patients. The overall quality of methodologies employed in the included studies was relatively high. 2. Meta-analysis results showed that electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD (SMD = -1.01, 95% CI − 1.78, − 0.25, P < 0.05). 3. This combination treatment demonstrated a significant positive effect on the improvement of pelvic floor muscle strength in female patients (P < 0.05); however, it had no significant effect on the improvement in quality of life (P > 0.05).

Conclusions

Compared with pelvic floor muscle exercise alone, electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD. It had a notable positive impact on enhancing pelvic floor muscle strength in female patients, although it did not significantly improve quality of life. Future high-quality studies are warranted.