bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the flipped classroom more effective than the traditional classroom in clinical medical education: a systematic review and meta-analysis
Authors: Shi Xu-Ying , Yin Qing , Wang Qiu-Wen , Lu Bing-Rui , Li Guo-Xiang , Huang Shu-Hong , Sun Zhi-Gang
Published: January 2025

Background

The flipped classroom teaching method has been increasingly adopted in recent years for teaching clinical medical specialties in medical schools around the world. However, the outcomes of this approach have not been systematically and quantitatively assessed. This meta-analysis aims to rigorously compare the effects of flipped classroom (FC) and traditional classroom (TC) teaching models on students’ learning in clinical medicine.

Methods

We conducted a systematic search for all randomized and quasi-randomized controlled trials (RCTs/Q-RCTs) comparing traditional classrooms and flipped classrooms in the context of clinical medical education. The literature search included the Cochrane Library, PubMed, Embase, and Web of Science, with the final retrieval conducted on October 26, 2024. We screened the literature based on predefined inclusion and exclusion criteria. The quality of each study was assessed using RevMan (Version 5.4). The outcome indicators included theoretical scores, composite scores, skills scores, and student satisfaction. Data extraction and subsequent meta-analysis were performed using Stata 17.0 software.

Results

A total of 12 studies were included in the analysis. The meta-analysis revealed that the flipped classroom (FC) group exhibited significantly higher theoretical scores (SMD = 0.481, 95% CI: 0.214 to 0.748, p = 0.000), composite scores (SMD = 0.642, 95% CI: 0.273 to 1.011, p = 0.001), and skills scores (SMD = 0.660, 95% CI: 0.312 to 1.008, p = 0.000) compared to the traditional classroom (TC) group. However, no statistically significant difference was observed in student satisfaction (SMD = −0.195, 95% CI: −1.081 to 0.691, p = 0.667).

Conclusion

The flipped classroom teaching method is more effective in enhancing the theoretical scores, composite scores, and skill scores of clinical medicine students compared to the traditional classroom teaching method. However, there was no statistically significant difference in student satisfaction between the two teaching approaches. Due to the limitations of the included studies, further robust randomized controlled trials (RCTs) across diverse educational contexts are necessary to validate these findings.
Emirates consensus recommendations on cardiovascular risk management in type 2 diabetes
Authors: Sabbour Hani , Almahmeed Wael , Alawadi Fatheya , Shehab Abdullah , Al Zubaidi Abdulamjeed , Bashier Alaaeldin , Ghulam Abdul Rauf , Rashid Fauzia , Zaky Hosam , Heshmat Kassemn Hussien , Adi Jamila Bin , Tahir Juwairia , Hafidh Khadija , Farghali Mohammed , Hassanien Mohamed , Januzzi James
Published: January 2025

Background

The combination of cardiovascular disease and diabetes is a highly prevalent condition in the United Arab Emirates. Development and dissemination of evidence-based regional recommendations for optimal screening, treatment and referrals of people with diabetes and high cardiovascular risk is an important priority.

Consensus panel

An expert panel of diabetologists, endocrinologists and cardiologists from the Emirates Cardiac Society and Emirates Diabetes and Endocrine Society as well as different entities in the UAE, discussed and reviewed evidence and also a consensus report from the American Diabetes Association to formulate contextualized recommendations that could be applied for optimal management of cardiovascular risk in people with diabetes in the UAE.

Consensus findings

The combination of heart failure and other cardiovascular risks is a highly prevalent finding among people with diabetes in the United Arab Emirates. The causal inter-relationships between diabetes and heart failure are multifactorial and regular assessments of symptoms and steps for mitigation of risk factors are an important priority. The universal definition and classification of heart failure provides a useful framework for recommending optimal screening, treatment, and referral strategies to diabetic individuals at various stages of the cardiovascular continuum. Routine measurement (at least yearly) of natriuretic peptides and high-sensitivity troponins can help identify patients requiring cardiac imaging referrals. However, recommending routine measurements of natriuretic peptides and/or high-sensitivity troponins to all diabetic individuals must balance clinical judgment and cost implications. While SGLT2i must be an important part of the standard of care, insulin, GLP1 receptor agonists and/or metformin can be useful for additional glycemic control.

Conclusion

The consensus panel hopes that the recommendations presented herein can offer guidance for optimal screening, treatment and referral of people with a concomitance of diabetes and high cardiovascular risk in the United Arab Emirates.
Exploring the altitude differentiation and influencing factors of PM2.5 and O3: a case study of the Fenwei Plain, China
Authors: Yin Zhenglin , Yuan Lei , Yang Yulian , Wu Xiaowei , Chen Zhiyong , Long Haixiao
Published: January 2025

Altitude differentiation has a substantial effect on the synergistic control of PM2.5 and O3 pollution. This study targets the Fenwei Plain, which is affected by mountain range blockage, divided into different altitude scales, and employs the methods of correlation analysis and geographical detector to explore the spatiotemporal heterogeneity of PM2.5 and O3 between different altitude zones and to identify the key controlling factors of pollutants between different altitude areas. The results showed that PM2.5 showed a significant decreasing trend from 2014 to 2023, whereas O3 exhibited an opposite trend. The concentrations of both pollutants decreased with increasing altitude, particularly for PM2.5, which showed significant altitudinal differentiation under the influence of topography. PM2.5 was negatively correlated with gross domestic product (GDP) and precipitation, and positively correlated with SO2. In contrast, the correlation of O3 with these factors was opposite to that of PM2.5. For spatial differentiation, NO2 and SO2 were the main factors influencing the spatial differentiation of PM2.5 and O3 at different altitudes. The explanatory power of the spatial divergence of PM2.5 and O3 was greatly increased by the interactions between the two precursors and between the precursors and meteorological factors. Furthermore, the explanatory power of the PM2.5 dominant factor increased with elevation, while the explanatory power of the O3 dominant factor was relatively high across low, middle, and high altitudes. This study serves as a guide for reducing air pollution in the Fenwei Plain and offers a novel perspective for the study of PM2.5 and O3 influenced by terrain.
How much to cut? Finding an optimal thinning intensity of encroaching woody species for the herbaceous community in an East African savanna
Authors: Abate Teshome , Abebe Tesfaye , Treydte Anna
Published: January 2025

Globally, bush encroachment poses a great threat to the conservation of biodiversity and rangeland productivity. However, control methods of encroaching woody species have rarely been experimentally quantified. We assessed the impact of tree thinning intensities on tree mortality, and the herbaceous community in Borana rangelands, an Ethiopian savannah ecosystem. At two 1.4 ha areas of mono-specific Vachellia drepanolobium stands, we set up 20 m x 10 m experimental plots with four tree-thinning treatments (0%, 33%, 67%, and 100% tree removal), with three replications in a randomized complete block design (RCBD) across two sites. The 0% plot was left uncleared and used as control. Over two growing periods, we monitored resulting tree mortality, coppicing, seedling mortality, and recruitment as well as herbaceous layer attributes (diversity, biomass) and the rangeland conditions. Tree thinning intensity significantly increased abundance of the dominant desirable grass species. Total herbaceous and grass species richness, diversity and biomass were significantly improved under high (100%) and moderate (67%) tree removal intensity. We conclude that tree thinning at moderate intensity (67%) was most effective in enhancing mortality of encroached trees, and improving grass diversity, and herbaceous biomass. We stress that effective tree thinning requires post-thinning management and repeated bush control measures. Our findings contribute to development of recommendations on controlling bush encroachment, species restoration, and rangeland productivity in Ethiopian rangelands.
TransferBAN-Syn: a transfer learning-based algorithm for predicting synergistic drug combinations against echinococcosis
Authors: Li Haitao , Chu Yuanyuan , Jiang Liyuan , Li Lei , Lv GuoDong , Liu Yuansheng , Zheng Chunhou , Su Yansen
Published: January 2025

Echinococcosis is a zoonotic parasitic disease caused by the larvae of echinococcus tapeworms infesting the human body. Drug combination therapy is highly valued for the treatment of echinococcosis because of its potential to overcome resistance and enhance the response to existing drugs. Traditional methods of identifying drug combinations via biological experimentation is costly and time-consuming. Besides, the scarcity of existing drug combinations for echinococcosis hinders the development of computational methods. In this study, we propose a transfer learning-based model, namely TransferBAN-Syn, to identify synergistic drug combinations against echinococcosis based on abundant information of drug combinations against parasitic diseases. To the best of our knowledge, this is the first work that leverages transfer learning to improve prediction accuracy with limited drug combination data in echinococcosis treatment. Specifically, TransferBAN-Syn contains a drug interaction feature representation module, a disease feature representation module, and a prediction module, where the bilinear attention network is employed in the drug interaction feature representation module to deeply extract the fusion feature of drug combinations. Besides, we construct a special dataset with multi-source information and drug combinations for parasitic diseases, including 21 parasitic diseases and echinococcosis. TransferBAN-Syn is designed and initially trained on the abundant data from the 21 parasitic diseases, which serves as the source domain. The parameters in the feature representation modules of drug interactions and diseases are preserved from this source domain, and those in the prediction module are then fine-tuned to specifically identify the synergistic drug combinations for echinococcosis in the target domain. Comparison experiments have shown that TransferBAN-Syn not only improves the accuracy of predicting echinococcosis drug combinations but also enhances generalizability. Furthermore, TransferBAN-Syn identifies potential drug combinations that hold promise in the treatment of echinococcosis. TransferBAN-Syn not only offers new synergistic drug combinations for echinococcosis but also provides a novel approach for predicting potential drug pairs for diseases with limited combination data.
Identification of key genes affecting intramuscular fat deposition in pigs using machine learning models
Authors: Shi Yumei , Wang Xini , Chen Shaokang , Zhao Yanhui , Wang Yan , Sheng Xihui , Qi Xiaolong , Zhou Lei , Feng Yu , Liu Jianfeng , Wang Chuduan , Xing Kai
Published: January 2025

Intramuscular fat (IMF) is an important indicator for evaluating meat quality. Transcriptome sequencing (RNA-seq) is widely used for the study of IMF deposition. Machine learning (ML) is a new big data fitting method that can effectively fit complex data, accurately identify samples and genes, and it plays an important role in omics research. Therefore, this study aimed to analyze RNA-seq data by ML method to identify differentially expressed genes (DEGs) affecting IMF deposition in pigs. In this study, a total of 74 RNA-seq data from muscle tissue samples were used. A total of 155 DEGs were identified using a limma package between the two groups. 100 and 11 significant genes were identified by support vector machine recursive feature elimination (SVM-RFE) and random forest (RF) models, respectively. A total of six intersecting genes were in both models. KEGG pathway enrichment analysis of the intersecting genes revealed that these genes were enriched in pathways associated with lipid deposition. These pathways include α-linolenic acid metabolism, linoleic acid metabolism, ether lipid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism. Four key genes affecting intramuscular fat deposition, PLA2G6, MPV17, NUDT2, and ND4L, were identified based on significant pathways. The results of this study are important for the elucidation of the molecular regulatory mechanism of intramuscular fat deposition and the effective improvement of IMF content in pigs.
Acute management of massive pulmonary embolism in pregnancy
Authors: Qadri Shahin , Bilagi Ashwini , Sinha Abha , Connolly Derek , Murrin Richard , Bakour Shagaf
Published: January 2025

Key content

•

Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but potentially lethal event.

•

Physiological changes in the coagulation system during pregnancy and puerperium would lead to a hypercoagulable state.

•

Diagnosis of PE in pregnancy remains a challenge due to physiological changes in pregnancy. There are no validated scoring systems for assessing pregnant/postpartum women with suspected PE. Massive PE should be suspected in all cases with haemodynamic instability in pregnancy.

•

The Management of massive pulmonary embolism should be timely and aggressive. Thrombolysis for massive PE during pregnancy and the postpartum period has shown to be associated with high maternal and fetal survival (94% and 88%). But other therapeutic options such as (catheter [or surgical] thrombectomy, ECMO) should be considered in the postpartum period, given the high risk of major bleeding with thrombolysis.

•

Thrombolysis remains the most-used and reasonably successful modality of treatment in pregnancy but should be avoided in the postpartum period as it can cause life-threatening haemorrhage. During the post-partum period, thrombectomy is the treatment of choice.

Learning objectives

•

To understand the pathophysiology of massive PE.

•

To appreciate the treatment options in pregnancy and postpartum period and their pros and cons.

•

To understand the need for further work in this area especially in creating a validated algorithm for diagnosing PE in pregnancy and postpartum period.
Integrating WHO thinking healthy programme for maternal mental health into routine antenatal care in China: a randomized-controlled pilot trial
Authors: Nisar Anum , Yin Juan , Zhang Jingjun , Qi Wenli , Yu Jie , Li Jiaying , Li Xiaomei , Rahman Atif
Published: January 2025

Background

Women with perinatal depression and their children are at increased risk of poor health outcomes. Integrating evidence based non-stigmatizing interventions within existing health systems is crucial to reducing psychosocial distress during pregnancy and preventing perinatal depression. This study aimed to evaluate the feasibility of the World Health Organization (WHO) endorsed cognitive-behavior therapy-based Thinking Healthy Programme (THP), delivered by antenatal nurses in China.

Methods

A two-arm pilot randomized controlled pilot trial was conducted to assess the feasibility and of the adapted Chinese version of the Thinking Healthy Programme (THP) among various stakeholders. We recruited pregnant women between 25- and 34-weeks' gestation from two pregnancy schools within the two public sector Hospitals in Xian. Participants in the intervention group attended five face to face sessions of THP facilitated by antenatal nurses. This intervention used cognitive behavior therapy principles to offer psychoeducation, behavioral activation, problem-solving strategies, and social support. In the control group, participants received standard care, which included routine pregnancy education classes led by antenatal nurses. We assessed depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9) at baseline, after the intervention and 4–6 weeks post-intervention, along with evaluations of anxiety, perceived social support, and health-related quality of life.

Results

Among the 737 pregnant women screened, 267 (30.26%) scored ≥5 on the PHQ-9. Out of these, 85 were eligible and consented to participate, with 42 assigned to the intervention group and 43 to the control group. Eighty participants (94.1%) completed the final assessments. Our primary findings indicated that this nurse-delivered intervention was feasible to integrate into routine antenatal care and was well-received by both the women and the delivery agents. Although the study was not designed to detect differences between the intervention and control groups, we observed positive trends towards reductions in anxiety and depressive symptoms favoring the intervention arm. No serious adverse events were reported. This trial is registered in the Chinese Clinical Trial Registry with the registration number ChiCTR1900028114.

Conclusions

We conclude that this intervention, grounded in the well-established WHO Thinking Healthy Programme, is both feasible and acceptable to stakeholders. It merits a definitive randomized trial to assess its effectiveness and cost-effectiveness across various settings.

Clinical Trial Registration

ChiCTR1900028114.
A gram-positive enhancer matrix particles vaccine displaying swine influenza virus hemagglutinin protects mice against lethal H1N1 viral challenge
Authors: Zhang Yufei , Zhang Pei , Du Xiaoyue , Shi Xiaona , Wang Jinling , Liu Shuying
Published: January 2025

Introduction

Animal influenza viruses pose a danger to the general public. Eurasian avian-like H1N1 (EA H1N1) viruses have recently infected humans in several different countries and are often found in pigs in China, indicating that they have the potential to cause a pandemic. Therefore, there is an urgent need to develop a potent vaccine against EA H1N1.

Methods

In this study, we report the effective intramuscular (i.m.) and/or intranasal (i.n.) vaccination of mice with a subunit influenza vaccine utilizing safe adjuvant gram-positive enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus lactis. The hemagglutinin (HA)-protein anchor (PA) subunit vaccine can be simply mixed with GEM particles to produce vaccines.

Results

After two booster injections, the i.m.+i.n. administered GEM subunit vaccine achieved hemagglutination inhibition titers in the serum that were equivalent to those observed using the conventional i.m. method. The mucosal and Th1-biased immune responses generated by the i.m. administered subunit vaccine alone were inferior to those induced by the i.n. and i.m.+i.n. administered subunit vaccines. Vaccinated mice were challenged with live viruses (G4 EA H1N1 and A/PR/8/34) to determine whether the adjuvant combination protected against the virus after vaccination with the influenza subunit vaccine. Compared to mice inoculated with HA alone, mice immunized with i.m.+i.n. or i.n. HA-PA-GEM displayed undetectable viral titers in the lungs, at 5 d after challenge.

Discussion

Overall, this study not only offers other potential platforms for the generation of swine influenza vaccines, but also a theoretical foundation for vaccine vector platforms that can be utilized for future research on other infections.
Single-cell sequencing analysis reveals cancer-associated pericyte subgroup in esophageal squamous cell carcinoma to predict prognosis
Authors: Xiong Kai , Pan Bing , Fang Hao , Tao Ziyou
Published: January 2025

Background

The role of cancer-associated pericytes (CAPs) in tumor microenvironment (TME) suggests that they are potential targets for cancer treatment. The mechanism of CAP heterogeneity in esophageal squamous cell carcinoma (ESCC) remains unclear, which has limited the development of treatments for tumors through CAPs. Therefore, a comprehensive understanding of the classification, function, cellular communication and spatial distribution of CAP subpopulations in ESCC is urgently needed.

Methods

This study used large-sample single-cell transcriptome sequencing (scRNA-seq) data to investigate pericytes’ subpopulation characteristics, functions, upstream and downstream regulation and interactions with other components of the TME in the ESCC, and analyzed prognostically in conjunction with Bulk RNA-seq data. In addition, pericyte subpopulations were validated and their spatial distribution in the ESCC TME was observed by multiplex immunofluorescence. Drug prediction and molecular docking was further used to validate the medicinal value of drug targets.

Results

CAPs in the ESCC TME were found to be highly heterogeneous, and we identified six pericyte subtypes: c1_ARHGDIB, c2_BCAM, c3_LUM, c4_SOD2, c5_TYMS, and c6_KRT17, which have commonality in a part of their functions, and each of them has a major function to play, by having different strengths of interaction with different components in the TME. In addition, we found that c4_SOD2 was negatively correlated with prognosis, conversely, c5_TYMS was positively correlated with prognosis. The drug with a better effect on c5_TYMS was docetaxel (binding energy = -8.1, -8.7 kcal/mol); raloxifene may be more effective against c4_SOD2, although raloxifene has a slightly lower binding energy to SOD2 (-6.4 kcal/mol), it has a higher binding energy to PDGFRβ (-8.1 kcal/mol).

Conclusion

The present study identified and discovered pericyte subpopulations that were significantly associated with prognosis, which provides new biomarkers for predicting patient prognosis and adds usable targets for immunotherapy, and it is also important for gaining insights into the composition of the TME in ESCC.
Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
Authors: Truglia Simona , Ciccia Francesco , Mancuso Silvia , Capozzi Antonella , Rizzo Aroldo , Spinelli Francesca Romana , Ceccarelli Fulvia , Colasanti Tania , Garufi Cristina , Miranda Francesca , Sorice Maurizio , Alessandri Cristiano , Conti Fabrizio
Published: January 2025

Introduction

Lupus nephritis (LN), caused by immune complexes produced in situ or deposited from the bloodstream, is one of the most severe features of Systemic Lupus Erythematosus (SLE) leading to an increased morbidity and mortality. Toll like receptors (TLRs), such as TLR3, TLR7 and TLR9, may play a key role in its pathogenesis. Interleukin-32 (IL-32), a cytokine involved in both innate and adaptive immune responses, has been widely considered in autoimmune-inflammatory rheumatic diseases. This study aims to evaluate the IL-32 role in LN, also investigating the effect of LN patients IgG (LN-IgG) on IL-32 production via TLR3.

Methods

In LN patients, IL-32 was detected in sera samples by ELISA KIT and in kidney tissue by immunohistochemistry. HEK293/T3 cells were incubated with LN-IgG and analyzed for TBK1, phospho-p65 NF-κB and IL-32 by Western blot.

Results

We demonstrated IL-32 presence in LN patients compared to SLE patients without renal involvement, observing a direct correlation between IL-32 serum levels and disease duration (p=0.02; r 0.2978). Moreover, IL-32 was strongly expressed in renal samples of LN patients. Phosphorylation of TBK1 resulting in NF-κB activation and IL-32 increase was observed in HEK293/T3 cells following LN-IgG treatment, TLR3 inhibitor using induced a significant reduction in the expression of these molecules.

Discussion

These results showed that IL-32 is up-regulated in the kidney of LN patients suggesting that in renal tissue IL-32 expression could be induced through TLR3 activation by the LN patients’ antibodies. This study may indicate a possible role for IL-32 in the pathogenesis of LN.
A nomogram model based on albumin-bilirubin score for predicting 90-day prognosis in patients with acute-on-chronic liver failure
Authors: Ding Wei , Shen Jiandong , Zhang Li , Shao Jianguo , Bian Zhaolian , Xue Hong
Published: January 2025

Objective

To develop a nomogram model based on the albumin-bilirubin (ALBI) score for predicting the 90-day prognosis of patients with acute-on-chronic liver failure (ACLF) and to evaluate its predictive efficacy.

Methods

Clinical data of 290 ACLF patients at the Third People’s Hospital of Nantong City, collected from December 2020 to December 2023, were analyzed. The data were divided into a training set (n = 200) and a validation set (n = 90), with August 2022 as the cut-off date. Patients in the training set were categorized into an improvement group (n = 133) and a mortality group (n = 67) based on their 90-day outcomes. The predictive power of baseline parameters was assessed using univariate and multivariate logistic regression to construct model. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and the Hosmer-Lemeshow test.

Results

Creatinine (CR) [odds ratio (OR) = 1.013, 95% confidence interval (CI): 1.004–1.022], ALBI (OR = 10.831, 95% CI: 4.009–33.247), Gender (OR = 1.931, 95% CI: 0.973–3.870) and ascites (OR = 3.032, 95% CI: 1.249–8.178) were identified as independent prognostic factors. The prognostic model formula was derived as prognostic index (PI) = –0.591 + 0.658 × Gender + 1.109 × ascites + 0.012 × CR + 2.382 × ALBI. The area under the curve (AUC) was 0.804 (95% CI: 0.741–0.866), with a specificity of 85.0% and a sensitivity of 65.7% at a cut-off of 0.425. The AUC of the validation set was 0.811 (95% CI: 0.697–0.926). The Hosmer-Lemeshow test indicated a good model fit with a p-value of 0.287 for the training set and 0.423 for the validation set. Calibration curves demonstrated the accuracy of the model, and DCA results suggested that the model was clinically useful when the threshold was below 0.6.

Conclusion

The nomogram model incorporating ALBI with CR, Gender and ascites can predict the 90-day prognosis of ACLF patients, potentially helping to optimize treatment strategies and improve patient outcomes.
A bibliometric analysis of optic atrophy from 2003 to 2023: research trends and hot spots
Authors: Wang Liyuan , Yu Tianyang , Wang Runze , Fu Lijuan , Dong Feixue , Zhao Shuang , Sun He , Gao Yang
Published: January 2025

Background

Optic atrophy (OA) is primarily caused by damage to the retinal pathway system, including widespread degeneration of retinal ganglion cells and axons, leading to visual impairment and blindness. Despite its clinical significance and diverse etiological factors, there is currently a lack of comprehensive bibliometric analyses exploring research trends and hotspots within this field.

Method

This study retrieved relevant literature on OA published between 2003 and 2023 from the Web of Science Core Collection database. We conducted a bibliometric analysis using tools such as CiteSpace, VOSviewer, and SCImago Graphica to examine annual publication trends, co-occurrence patterns, collaborative networks among countries and institutions, and the evolution of research hotspots of OA.

Results

A total of 5,274 publications were included in the bibliometric analysis, comprising 4,561 research articles and 713 review articles. The United States emerged as the leading country in OA research, followed by Germany and China. Over the past two decades, the primary research hotspots focused on “mitochondrial dysfunction,” “hereditary optic neuropathy,” “ocular hypertension” and “diagnostic techniques.” Future research trends are likely to revolve around “molecular mechanisms” and “therapeutic targets.”

Conclusion

This bibliometric analysis provides an overview of research developments in OA over the past 20 years, highlighting the emphasis on the pathological basis of OA and advancements in diagnostic and therapeutic approaches. Future studies should continue to explore the molecular basis of mitochondrial dysfunction to identify potential gene therapy targets for treating OA.
Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development
Authors: Elbehiry Ayman , Marzouk Eman , Abalkhail Adil , Sindi Wael , Alzahrani Yasir , Alhifani Salem , Alshehri Turki , Anajirih Nuha Abdulaziz , ALMutairi Turki , Alsaedi Ahmad , Alzaben Feras , Alqrni Abdullah , Draz Abdelmaged , Almuzaini Abdulaziz M. , Aljarallah Sahar N. , Almujaidel Abdulrahman , Abu-Okail Akram
Published: January 2025

One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.
Understanding the limitations of substrate degradation in bioelectrochemical systems
Authors: Bird Hannah , Velasquez-Orta Sharon , Heidrich Elizabeth
Published: January 2025

Microbial Fuel Cells (MFCs) are innovative environmental engineering systems that harness the metabolic activities of microbial communities to convert chemical energy in waste into electrical energy. However, MFC performance optimization remains challenging due to limited understanding of microbial metabolic mechanisms, particularly with complex substrates under realistic environmental conditions. This study investigated the effects of substrate complexity (acetate vs. starch) and varying mass transfer (stirred vs. non-stirred) on acclimatization rates, substrate degradation, and microbial community dynamics in air-cathode MFCs. Stirring was critical for acclimating to complex substrates, facilitating electrogenic biofilm formation in starch-fed MFCs, while non-stirred MFCs showed limited performance under these conditions. Non-stirred MFCs, however, outperformed stirred systems in current generation and coulombic efficiency (CE), especially with simple substrates (acetate), achieving 66% CE compared to 38% under stirred conditions, likely due to oxygen intrusion in the stirred systems. Starch-fed MFCs exhibited consistently low CE (19%) across all tested conditions due to electron diversion into volatile fatty acids (VFA). Microbial diversity was higher in acetate-fed MFCs but unaffected by stirring, while starch-fed MFCs developed smaller, more specialized communities. Kinetic analysis identified hydrolysis of complex substrates as the rate-limiting step, with rates an order of magnitude slower than acetate consumption. Combined hydrolysis-fermentation rates were unaffected by stirring, but stirring significantly impacted acetate consumption rates, likely due to oxygen-induced competition between facultative aerobes and electrogenic bacteria. These findings highlight the trade-offs between enhanced substrate availability and oxygen-driven competition in MFCs. For real-world applications, initiating reactors with dynamic stirring to accelerate acclimatization, followed by non-stirred operation, may optimize performance. Integrating MFCs with anaerobic digestion could overcome hydrolysis limitations, enhancing the degradation of complex substrates while improving energy recovery. This study introduces novel strategies to address key challenges in scaling up MFCs for wastewater treatment, bridging the gap between fundamental research and practical applications to advance environmental systems.
Robot-assisted upper limb therapy for personalized rehabilitation in children with cerebral palsy: a systematic review
Authors: Cardone Daniela , Perpetuini David , Di Nicola Marta , Merla Arcangelo , Morone Giovanni , Ciancarelli Irene , Moretti Antimo , Gimigliano Francesca , Cichelli Alice , De Flaviis Francesco , Martino Cinnera Alex , Paolucci Teresa
Published: January 2025

Introduction

Cerebral palsy (CP) is a group of permanent disorders of movement development that may cause activity limitations. In this context, robot-assisted therapy might play a key role in clinical management. This comprehensive systematic review aimed to investigate the efficacy of robotic systems in improving upper limb (UL) functions in children with CP.

Methods

PubMed, EMBASE, Scopus, and PEDro were searched from inception to February 2024. The risk of bias was assessed with the Joanna Briggs Institute critical appraisal tools battery.

Results

Of 756 articles identified, 14 studies involving 193 children with CP with a judged to be of good methodological quality, but with a lack in the study design, were included in the final synthesis. In the included studies a wide range of devices was used, both exoskeletons and end-effectors, both wearable and non-wearable. The CP children who underwent robot-assisted therapy reported a significant overall increase in clinical assessment, specifically in UL movements and manual dexterity. The clinical improvement was often accompanied by a gain also in instrumental assessments (i.e., kinematic analysis, EMG).

Discussion

The present review suggested that robot-assisted therapy can improve UL motor functions in children with CP. Moreover, the availability of different devices with adjustable parameters can represent an important resource in proposing patient-centered-personalized rehabilitation protocols to enhance the efficacy of rehabilitation and integration into daily life. However, the limited sample size and lack of standardized and clearly reproducible protocols impose to recommend the use of robot-assisted therapy as an integration to usual rehabilitation and not as a replacement.

Systematic review registration

https://osf.io/a78zb/.
Local abnormal white matter microstructure in the spinothalamic tract in people with chronic neck and shoulder pain
Authors: Qiu Zhiqiang , Liu Tianci , Zeng Chengxi , Yang Maojiang , Xu Xiaoxue
Published: January 2025

Objective

To investigate differences in the microstructure of the spinothalamic tract (STT) white matter in people with chronic neck and shoulder pain (CNSP) using diffusion tensor imaging, and to assess its correlation with pain intensity and duration of the pain.

Materials and methods

A 3.0T MRI scanner was used to perform diffusion tensor imaging scans on 31 people with CNSP and 24 healthy controls (HCs), employing the Automatic Fiber Segmentation and Quantification (AFQ) method to extract the STT and quantitatively analyze the fractional anisotropy (FA) and mean diffusivity (MD), reflecting the microstructural integrity of nerve fibers. Correlations of these differences with duration of pain and visual analog scale (VAS) scores were analyzed.

Results

No significant differences in the mean FA or MD values of the bilateral STT were observed between people with CNSP and HCs (p > 0.05), as indicated by the two-sample t test. Further point-by-point comparison along 100 equidistant nodes within the STT pathway revealed significant reductions in FA values in the left (segments 12–18, 81–89) and right (segments 9–19, 76–80) STT in the CNSP group compared to HCs; significant increases in MD values were observed in the left (segments 1–13, 26–30, 71–91) and right (segments 8–17, 76–91) STT (p < 0.05, FWE corrected). Partial correlation analysis indicates that in people with CNSP, the FA values of the STT in regions with damaged white matter structure show a negative correlation with VAS scores and duration of pain, whereas MD values show a positive correlation with VAS scores and duration of pain.

Conclusion

This study found that people with CNSP exhibit white matter microstructural abnormalities in the specific segments of STT. These abnormalities are associated with the patient’s pain intensity and disease duration. The findings offer a new neuroimaging perspective on the pathophysiological basis of chronic pain in the ascending conduction process and its potential role in developing targeted intervention strategies. However, due to the limited sample size and the lack of statistical significance when analyzing the entire spinothalamic tract, these conclusions should be interpreted with caution. Further research with larger cohorts is necessary to validate these results.
Sulforaphane acutely activates multiple starvation response pathways
Authors: Plafker Kendra S. , Georgescu Constantin , Pezant Nathan , Pranay Atul , Plafker Scott M.
Published: January 2025

Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables that has demonstrated anti-cancer, anti-microbial and anti-oxidant properties. SFN ameliorates various disease models in rodents (e.g., cancer, diabetes, seizures) that are likewise mitigated by dietary restrictions leading us to test the hypothesis that this compound elicits cellular responses consistent with being a fasting/caloric restriction mimetic. Using immortalized human retinal pigment epithelial cells, we report that SFN impacted multiple nutrient-sensing pathways consistent with a fasted state. SFN treatment (i) increased mitochondrial mass and resistance to oxidative stress, (ii) acutely suppressed markers of mTORC1/2 activity via inhibition of insulin signaling, (iii) upregulated autophagy and further amplified autophagic flux induced by rapamycin or nutrient deprivation while concomitantly promoting lysosomal biogenesis, and (iv) acutely decreased glucose uptake and lactate secretion followed by an adaptive rebound that coincided with suppressed protein levels of thioredoxin-interacting protein (TXNIP) due to early transcriptional down-regulation. This early suppression of TXNIP mRNA expression could be overcome with exogenous glucosamine consistent with SFN inhibiting glutamine F6P amidotransferase, the rate limiting enzyme of the hexosamine biosynthetic pathway. SFN also altered levels of multiple glycolytic and tricarboxylic acid (TCA) cycle intermediates while reducing the inhibitory phosphorylation on pyruvate dehydrogenase, indicative of an adaptive cellular starvation response directing pyruvate into acetyl coenzyme A for uptake by the TCA cycle. RNA-seq of cells treated for 4 h with SFN confirmed the activation of signature starvation-responsive transcriptional programs. Collectively, these data support that the fasting-mimetic properties of SFN could underlie both the therapeutic efficacy and potential toxicity of this phytochemical.
Association between Life’s Crucial 9 and overactive bladder: the mediating role of weight-adjusted-waist index
Authors: Gong Hongyang , Duan Shuqin , Huang Shaoqun
Published: January 2025

Background

Research suggests a potential connection between cardiovascular health, obesity, and overactive bladder (OAB). However, the mechanisms by which obesity influences the relationship between cardiovascular health and OAB remain unclear. Life’s Crucial 9 (LC9) is a recently proposed method for assessing cardiovascular health, while the weight-adjusted waist index (WWI) is a novel and more accurate measure of obesity. This study investigates the relationship between LC9 and OAB and assesses whether WWI moderates this relationship.

Methods

Data for this study came from the National Health and Nutrition Examination Survey (NHANES). We used subgroup analyses, restricted cubic spline curves (RCS), and multivariate logistic regression to explore the relationship between LC9 and OAB. Additionally, mediation analysis was conducted to investigate the potential association between WWI levels and the relationship between LC9 and OAB.

Results

A total of 25,319 participants were included in this study, among which 5,038 reported incidents of OAB. After adjusting for all variables using multivariable logistic regression, an increase of 10 units in LC9 was associated with a 28% reduction in the incidence of OAB (OR = 0.72, 95% CI: 0.69, 0.76), while an increase of one unit in WWI was associated with a 40% increase in the incidence of OAB (OR = 1.40, 95% CI: 1.29, 1.51). Consistent results were also observed when LC9 and WWI were categorized into quartiles, with a P for trend <0.001. The analysis using restricted cubic splines indicated a linear negative correlation between the incidence of OAB and LC9. Mediation analysis revealed that 13.89% of the relationship between LC9 and OAB was mediated by WWI (p = 0.002).

Conclusion

This study found a significant negative correlation between LC9 and OAB, with WWI acting as a partial mediator in this relationship. This study provides new insights for future research into the relationship between LC9 and OAB and the role of WWI as a mediator.
Prognostic risk factors of pneumonia associated with COVID-19 in patients with lymphoma
Authors: Liu Dan , Yin Xia , Wang Hui , Xing Lijie , Li Ping , Wei Haichen , Ma Ji , He Qiang , Xie Linna , Lu Ke , Li Zengjun
Published: January 2025

Objective

Patients with hematological malignancies have an elevated risk of developing pneumonia after contracting COVID-19. Lymphoma is the most prevalent hematologic malignancy. It is critical to identify patients at high risk of contracting COVID-19-associated pneumonia.

Methods

From January 11–31, 2023, we distributed questionnaires to patients diagnosed with lymphoma according to 2016 World Health Organization diagnostic and classification criteria. COVID-19 infection was confirmed based on symptoms and laboratory tests. Pneumonia was confirmed using computed tomography scans.

Results

In total, 257 patients were included in this study; 221 patients (86.0%) had COVID-19 infection and 61 (27.6%) of these had pneumonia. Patients with B-cell non-Hodgkin lymphoma (B-NHL) had a significantly higher pneumonia incidence than patients with other lymphoma types (31.8% vs. 27.6%, P=0.005). Higher incidence of pneumonia was observed in patients receiving anti-CD20 therapy (30.0% vs. 16.3%, P=0.048) and Bruton’s tyrosine kinase (BTK) inhibitor therapy (51.3% vs. 22.5%, P=0.001). B-NHL (hazard ratio [HR]=3.7, 95% confidence interval [CI] 1.4–10.0, P=0.009), anti-CD20 therapy (HR=2.3, 95% CI 1.0–5.2, P=0.050), BTK inhibitor (HR=3.6, 95% CI 1.8–7.4, P<0.001), active therapy (HR=3.0, 95% CI 1.5–5.7, P=0.001), and lack of disease remission (HR=3.7, 95% CI 1.8–7.4, P=0.001) were high-risk factors for developing pneumonia. Anti-PD-1 therapy was a protective factor against pneumonia development (HR=0.2, 95% CI 0.05–0.9, P=0.034). In multivariable analysis, BTK inhibitor (HR=3.5, 95% CI 1.6–8.0, P=0.003), active therapy (HR=3.3, 95% CI 1.6–6.8, P=0.001), and disease non-remission (HR=2.9, 1.3–6.4, P=0.007) were independent risk factors for pneumonia development after COVID-19 infection in patients with lymphoma.

Conclusions

Patients with lymphoma receiving BTK inhibitors, undergoing active therapy, and lacking disease remission exhibited a higher risk for pneumonia associated with COVID-19.
Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors
Authors: O’Halloran Katrina , Crotty Erin E. , Christodoulou Eirini , Leary Sarah E. , Miller Alexandra , Paulson Vera A. , Lockwood Christina M. , Margol Ashley S. , Biegel Jaclyn A.
Published: January 2025

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors. These include polymerase chain reaction (PCR), both droplet digital PCR and reverse transcription-based PCR, Sanger sequencing, and next-generation sequencing approaches that incorporate amplicon- and hybrid capture-based methods. The goal of this paper is to facilitate an understanding of these targeted techniques and provide a context for clinical relevance within disease categories, as well as a discussion on optimizing real-world implementation for pediatric CNS tumors.
IDH-mutant gliomas in children and adolescents - from biology to clinical trials
Authors: Evans Louise , Trinder Sarah , Dodgshun Andrew , Eisenstat David D. , Whittle James R. , Hansford Jordan R. , Valvi Santosh
Published: January 2025

Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (IDH), with mutated IDH (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors. Despite their rarity, IDH mutations have been reported in 5-15% of pediatric glioma cases. Those with primary mismatch-repair deficient mIDH astrocytomas (PMMRDIA) have a particularly poor prognosis. Here, we describe the biology of mIDH gliomas and review the literature regarding the emergence of mIDH inhibitors, including clinical trials in adults. Given the paucity of clinical trial data from pediatric patients with mIDH glioma, we propose guidelines for the inclusion of pediatric and AYA patients with gliomas onto prospective trials and expanded access programs as well as the potential of combined mIDH inhibition and immunotherapy in the treatment of patients with PMMRDIA at high risk of progression.