bluuebunny/crossref_metadata_2025 huggingface dataset:
Chaihuang Qingyi Huoxue granule ameliorates severe acute pancreatitis by modulating gut microbiota and repairing the intestinal mucosal barrier
Authors: Zhang Xiaobin , Zeng Xusen , Guo Wen , Zhou Xin , Zhang Yi , Tang Mingyun , Fu Juan , Deng Yuqing , Liang Xin , Zhao Long , Li Zhi , Wang Tiangang , Li Li , Xiao Guohui
Published: February 2025

Background

During severe acute pancreatitis (SAP), damage to the intestinal mucosal barrier and translocation of intestinal pathogenic bacteria are key mechanisms that accelerate the disease progression of SAP. Chaihuang Qingyi Huoxue Granule (CH) is a herbal formula used in the clinical treatment of SAP. This study aims to investigate the role of CH in regulating gut microbiota and intestinal mucosal barrier in SAP rats.

Methods

Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. CH (4.4 g/kg) was administered by gavage. Serum amylase, lipase, and endotoxin levels were measured. Hematoxylin-eosin (HE) staining was used to observe morphological changes in the pancreas and colon. The expression of zona occludens-1 (ZO-1) and occludin in the colon was examined by immunohistochemistry (IHC) and western blot. 16S rDNA gene sequencing was used to analyze the gut microbiota of the rats. The content of short-chain fatty acids (SCFAs) in the intestinal contents of the rats was determined by gas chromatography-mass spectrometry (GC-MS).

Results

CH reduced serum amylase, lipase, and endotoxin levels in SAP rats, alleviated pathological damage in the pancreas and colon, and restored the expression of ZO-1 and occludin. Moreover, CH alleviated gut microbiota dysbiosis in SAP rats, with restored gut microbiota diversity and structure. At the phylum level, the relative abundance of Firmicutes and Bacteroidetes increased, while that of Proteobacteria decreased. At the genus level, the abundance of Ruminococcus 1, Parabacteroides, Prevotellaceae UCG-001, Lachnospiraceae NK4A136 group, and Lactobacillus increased, while that of Escherichia-Shigella, Enterococcus, and Enterobacter decreased. In addition, CH increased the levels of SCFAs in the intestinal contents of SAP rats.

Conclusion

CH ameliorates SAP by maintaining the homeostasis and diversity of the gut microbiota, increasing the levels of SCFAs, and repairing the intestinal mucosal barrier.
Characteristic profiles of molecular types, antibiotic resistance, antibiotic resistance genes, and virulence genes of Staphylococcus aureus isolates from caprine mastitis in China
Authors: Shi Hongfei , Wang Long , Li Guoguang , Li Dandan , Zhai Hongyue , Ji Shidong , Hu Yun , Lv Tingting , Yao Lunguang
Published: February 2025

Staphylococcus aureus is a significant pathogen in dairy animals, particularly when it infects the mammary gland; however, its prevalence among dairy goats in China remains poorly understood. This study aimed to investigate the distribution and characteristics of S. aureus isolates in dairy goats across China. A total of 515 milk samples were collected from goats diagnosed with mastitis in 14 provinces. These samples underwent bacterial isolation and identification, capsular polysaccharides typing, spa typing, antimicrobial susceptibility testing, and assessment of antimicrobial resistance and virulence gene. The findings revealed the isolation of 61 S. aureus strains. The highest prevalence rate was recorded in 2018, at 20.4% (11 out of 54 samples), while the lowest prevalence rate was noted in 2023, at 5.2% (3 out of 58 samples). Among the five regions studied, southern China exhibited the highest prevalence rate of 17.5% (10 out of 57 samples), whereas northeastern China showed the lowest rate at 8.2% (8 out of 97 samples). Capsular polysaccharide type 5 emerged as the most prevalent, accounting for 52.5%, and spa type t521 was identified most frequently, at 19.7%. Notably, 52 isolates (85.2%) demonstrated multidrug resistance, displaying resistance to three or more antibiotics. The resistance rates of S. aureus isolates were significantly high to penicillin (95.1%), followed by enrofloxacin (82.0%), kanamycin (78.7%), and levofloxacin (77.0%). Trimethoprim-sulfamethoxazole exhibited the lowest resistance rate at 11.5%. Resistance rates varied across the five different regions. Additionally, eight genes associated with resistance to six classes of antimicrobials were detected, with the blaZ gene (93.4%) being the most prevalent at 93.4%. Furthermore, nine virulence-associated genes were identified, with clfA being the most common virulence gene, present in all isolates. In conclusion, most S. aureus isolates were multiresistant with diverse resistance patterns. Those diverse antimicrobial resistance profiles associated with corresponding resistance genes (p < 0.05) were reported for the first time in S. aureus from caprine mastitis. Sulfonamides could be prioritized preferentially for the treatment of S. aureus mastitis.
Changes of metabolic parameters, antioxidant capacity, and gut microbiota in response to substitution of ferrous sulfate with iron hydroxy methionine analog chelate in weaned piglets
Authors: Fu Yuemeng , Zhou Guohui , Liu Yuhang , Yuan Xuejun , Jiao Ning , Lu Wenbiao , Yang Weiren
Published: February 2025

Introduction

Previous studies have suggested that dietary organic iron offers health advantages compared to its inorganic counterpart. However, the effects of iron hydroxy methionine analog chelate (Fe-HMA) supplementation in weaned piglets have not been fully explored. Therefore, this study aimed to investigate the effects of replacing ferrous sulfate with Fe-HMA as the iron source on serum biochemistry, antioxidant capacity, and gut microbiota in weaned piglets.

Methods

One hundred and twenty weaned piglets were randomly allocated to two treatment groups. Each group contained four replicates, with 15 pigs per replicate. Piglets were fed either 100 mg Fe/kg in the form of ferrous sulfate (Fe-sulfate group) or 50 mg Fe/kg in the form of Fe-HMA (Fe-HMA group) as the iron source for 28 days.

Results and discussion

Results showed that supplementing Fe-HMA as an iron source significantly increased the levels of triglycerides and glucose in portal venous serum, albumin in both serum and portal venous serum and decreased serum low-density lipoprotein level in weaned piglets. Additionally, Fe-HMA supplementation significantly reduced serum and liver malondialdehyde levels, while increasing catalase (CAT), glutathione peroxidase (GSH-Px), total superoxide dismutase, and manganese superoxide dismutase levels in serum, as well as GSH-Px and CAT levels in the liver. Moreover, Fe-HMA regulated the intestinal microbiota composition, notably increasing the relative abundance of Proteobacteria and decreasing microbes involved in aromatic_compound_degradation. In conclusion, dietary replacing inorganic iron with Fe-HMA improved metabolic parameters and antioxidant capacity, and regulated gut microbiota composition in weaned piglets.
Land-based climate mitigation strategies for achieving net zero emissions in India
Authors: Jaiswal Deepak , Siddique Khadeeja Mol , Jayalekshmi T. R. , Sajitha A. S. , Kushwaha Amit , Surendran Sruthi
Published: February 2025

Despite advancements in electrification and the transition to solar-based electricity production, India will continue to depend on land-based carbon offsets to achieve its net-zero target. Land-based climate mitigation strategies in India can be implemented by utilizing underutilized marginal lands or increasing land availability through technological interventions to close agricultural yield gaps. Both below-ground (e.g., soil carbon) and above-ground (e.g., standing tree biomass) options offer viable pathways for such measures. Key strategies include cultivating perennial bioenergy feedstocks, afforestation, establishing fast-growing Miyawaki forests, restoring wetlands and mangroves, and applying biosolids to land. However, caution is essential to prevent unintended consequences, such as clearing natural forests or introducing microplastics into soils. The cost of carbon sequestration and the resilience or permanence of stored carbon will be critical factors in determining the preferred approach. Additionally, land-based strategies often overlap spatially, making GIS-based tools indispensable for identifying optimal solutions tailored to local conditions. Integrating these strategies into the national carbon budget can enhance transparency and contribute significantly to India’s net-zero emissions goal.
P-selectin glycoprotein ligand-1 and cardiovascular diseases: from a general perspective to an HIV infection context
Authors: Zaongo Silvere D. , Song Yuxia , Chen Yaokai
Published: February 2025

Globally, cardiovascular diseases (CVDs) are a leading cause of death as they are responsible for the loss of at least 17 million lives annually. It has been established that the pathogenesis of CVDs is strongly associated both with inflammation as well as with inflammatory markers (proteins, cytokines, amongst others). In this perspective, the role of one of these proinflammatory proteins, referred to as P-selectin glycoprotein ligand (PSGL)-1, is of particular interest. Indeed, contemporary evidence points to the fact that P-selectin glycoprotein ligand (PSGL)-1 plays a critical role in the development of CVDs via its interactions with P-selectin, L-selectin, and/or E-selectin. However, due to the dearth of published contemporary research concerning PSGL-1 expression in people living with HIV (PLWH), it remains challenging to comprehensively investigate this area of study, although potential clues exist in the literature which may serve as potential directions for future investigations. Hence, in the first part of this article, a scoping review of the literature regarding the role of PSGL-1 in the development of CVDs is provided. Then, in the second part, observations concerning PSGL-1 expression in PLWH receiving ART are presented and interpreted. Through this work, we hope that increased attention will be directed towards the screening of PSGL-1 expression, which we believe may serve as a reliable biomarker to predict the presence and evolution of CVDs in PLWH.
Optimized workflow for paroxysmal atrial fibrillation ablation using very high power short duration
Authors: Gigli Lorenzo , Preda Alberto , Testoni Alessio , Kotinas Alexios Sotirios , Tacchetto Andrea , Guarracini Fabrizio , Carbonaro Marco , Vargiu Sara , Varrenti Marisa , Colombo Giulia , Menè Roberto , Baroni Matteo , Frontera Antonio , Mazzone Patrizio
Published: February 2025

Background

wide antral pulmonary vein isolation (PVI) is effective for treating paroxysmal atrial fibrillation (PAF), although time-demanding. We investigated the impact of a standardized ablation protocol by using a bidirectional transeptal steerable sheath, high-density mapping and very high-power-short-duration (vHPSD) catheters on procedure timing, efficacy, and safety.

Methods

consecutive PAF patients free from previous ablations undergoing PVI alone between January 2022 and March 2023 were prospectively enrolled. The standardized workflow included general anesthesia, a single transeptal puncture trough with a bidirectional, steerable visualizable sheath introduced into the left atrium accommodated a high density, penta-spline mapping catheter and a contact force sensor ablation catheter enabled to deliver vHPSD. Procedural data and electrophysiology (EP) laboratory times were systematically collected and analyzed. The primary endpoint was any AF or atrial tachycardia recurrence at 12 and 24 month follow up.

Results

the study cohort was composed by 138 patients (mean age was 59 ± 11 years, 38% female) and successful PVI was achieved in 100% of cases. Overall, first pass isolation (PFI) was 93%, with a LA dwell time of 32 ± 4 min. Significant complications were reported in 3% of patients. Skin-to-skin time and total EP laboratory time were 58 ± 5 min and 85 ± 7 min, respectively. The primary endpoint was achieved by 9% and 12% of cases at 12 and 24 month follow up, respectively. Upper limit skin-to-skin time and missed FPI resulted predictors of the primary endpoint.

Conclusion

This standardized workflow resulted in low procedural times and arrhythmias recurrence without compromising the safety.
Virtual reality for training emergency medicine residents in emergency scenarios: usefulness of a tutorial to enhance the simulation experience
Authors: Vittadello A. , Savino S. , Bressan S. , Costa M. , Boscolo A. , Sella N. , Pettenuzzo T. , Zarantonello F. , De Cassai A. , Chang T. , Navalesi P. , Mormando G.
Published: February 2025

Introduction

Critical events in healthcare require a rapid and coordinated approach: simulation has been demonstrated a valid technique for training in emergency. Virtual Reality (VR) is an innovative technology that has revolutionized simulation training and healthcare professional development. A key phase of a simulation session with manikin consists in a familiarization with setting and equipment. The primary objective of this study is to investigate whether familiarization with a VR tutorial can change the perception of cases.

Methods

Emergency medicine residents were randomly assigned to the Intervention group (n = 21) who undergone familiarization tutorial prior to the clinical scenario to a Control group (n = 21) where no familiarization tutorial was provided before the clinical scenario.

Results

No significant differences were found between the two groups regarding perceived ease of use, but the Intervention group found VR familiarization useful and the Control group found it necessary to implement a VR tutorial. VR training was generally perceived by learners as a useful technology for training as confirmed by the literature.

Discussion

Familiarization seems to be an important phase of simulation-based training for trainees, even when running a VR-based simulation for an emergency scenario; it should be incorporated into the clinical VR sessions for simulation in healthcare settings.
Developing and testing tele-support psychotherapy using mobile phones for depression among youth in Kampala district, Uganda: study protocol for a pilot randomized controlled trial
Authors: Nakimuli-Mpungu Etheldreda , Kwesiga Jeremiah Mutinye , Bwanika John Mark , Musinguzi Davis , Nakanyike Caroline , Iya Jane , Bakeera Kitaka Sabrina , Akimana Benedict , Hawkins Charlotte , Cavazos Patricia , Nachega Jean B. , Mills Edward J. , Seggane Musisi
Published: February 2025

Introduction

In the post-COVID-19 era, depressive disorders among youth have risen significantly, creating an urgent need for accessible, cost-effective mental health interventions. This study adapts Group Support Psychotherapy into Tele-Support Psychotherapy (TSP) via mobile phones. It aims to evaluate its feasibility, acceptability, effectiveness, and cost-efficiency in addressing mild to moderate depression among youth in central Uganda.

Methods and analysis

This study will use a mixed-methods approach, starting with a qualitative phase to adapt Group Support Psychotherapy into Tele-Support Psychotherapy (TSP) via mobile phones. Guided by ecological theories and the Unified Theory of Acceptance and Use of Technology (UTAUT), focus group discussions and interviews with youth, mental health professionals, and stakeholders will inform the development of a youth-tailored call platform integrated into Rocket Health Africa's telehealth services. Data will be analyzed using grounded theory and MAXQDA Analytics Pro 2022 to guide intervention adaptation. An open-label randomized controlled trial will enroll 300 youth (15–30 years) with mild to moderate depression from Kampala, Uganda, to evaluate Tele-Support Psychotherapy (TSP). Participants will be randomized to TSP with standard mental health services (SMHS) or SMHS alone. Primary outcomes include feasibility and acceptability, with secondary outcomes assessing cost-effectiveness, depressive symptom changes, and social support. Intention-to-treat analysis using structural equation modeling will evaluate treatment effects, complemented by qualitative insights into implementation barriers and facilitators.

Discussion

This study protocol develops and evaluates Tele-Support Psychotherapy (TSP) for youth depression in resource-limited settings, addressing mental health gaps exacerbated by COVID-19. Using user-centered design and mixed methods, it explores TSP's feasibility, adaptability, and cost-effectiveness while addressing barriers like technology literacy, laying the groundwork for accessible digital mental health solutions.

Trial Registration

PACTR202201684613316.
Bridging language barriers in healthcare: a patient-centric mobile app for multilingual health record access and sharing
Authors: Solomou Theodoros , Mappouras Stelios , Kyriacou Efthyvoulos , Constantinou Ioannis , Antoniou Zinonas , Canciu Ionut Cristian , Neophytou Marios , Lantos Zoltan , Schizas Christos N. , Pattichis Constantinos S.
Published: February 2025

Introduction

Access to health data for patients is hindered by a fragmented healthcare system and the absence of unified, patient-centric solutions. Additionally, there are no mechanics for easy sharing of medical records with healthcare providers, risking incomplete diagnoses. To further intensify the problem, when patients seek care abroad, language barriers may prevent foreign doctors from understanding their health data, further complicating treatment.

Methods

Our study presents the development and evaluation of a mobile application designed to enable users to access and share their health records directly from their device, in multiple languages, ensuring ease of use and convenience. The solution utilizes OpenNCP for translating patient summaries into multiple languages and the FHIR Smart Health Links Protocol for secure sharing. We conducted a user acceptance study with 45 participants to evaluate our mobile app's interface and functionality.

Results

The feedback was positive, highlighting the app's user-friendliness and usefulness. The participants felt it would enhance communication between physicians and patients and the features of sharing and translating are going to give more control of their medical data to the patients.

Discussion

Based on the results and participants feedback, our mobile solution significantly enhances healthcare accessibility and efficiency by enabling easy access and sharing of health records in multiple languages, using relevant protocols and standards, reducing medical errors and ensuring personalized care.
Generation mechanism and influencing factors of transient overvoltage on ultra high-voltage direct current transmission
Authors: Yao Weiwei , Zhao Jie , Dou Jinqiu , Deng Youhan , Li Yushu , Liang Yilin , Chen Jing
Published: February 2025

The transient overvoltage caused by faults in ultra-high-voltage direct current (UHVDC) transmission lines and alternating current (AC) systems can adversely affect system safety and stability. This study theoretically analyzes the transient overvoltage generation mechanism caused by DC single-pole ground faults and typical fault conditions in two different cases by combining the DC line and AC system of the transmitting side. Considering the different generation mechanisms of the two transient overvoltages, the main factors affecting transient overvoltages were determined to be the DC line ground fault location, DC filter main capacitance, AC system short-circuit ratio, and DC transmission power. Finally, through a simulation of UHVDC transmission engineering, the relationship between various influencing factors and overvoltage was obtained, which can provide guidance in transmission engineering UHVDC design.
Using nature-based citizen science initiatives to enhance nature connection and mental health
Authors: Oh Rachel R. Y. , Suarez-Castro Andres F. , Fuller Richard A. , Tervo Michael , Rozario Kevin , Peters Birte , Chowdhury Shawan , von Gönner Julia , Friedrichs-Manthey Martin , Berger Ambros , Schultz Tracy , Dean Angela J. , Tulloch Ayesha , Bonn Aletta
Published: February 2025

The global rise in mental health issues underscores the critical importance of assessing the mental health benefits of engaging with nature. Beyond their primary aim of involving citizens in scientific data collection, nature-based citizen science initiatives offer significant potential for enhancing outcomes related to conservation (e.g., connection to nature) and human health and wellbeing (e.g., emotions, depression, stress, anxiety). However, the effectiveness of various types of initiatives in achieving specific outcomes remain unclear. This study evaluates changes in eight outcomes related to nature connection and health and wellbeing before and after participation in five initiatives in Australia and Germany. These initiatives varied in ecosystem type (urban parks, terrestrial forests and freshwater streams) and the participation duration (from 15 min to 48 h). We assessed three dimensions of connection to nature (Self, Experience and Perspective) measured by the Nature-Relatedness scale, mental health outcomes (symptoms of depression, stress and anxiety) using the DASS-21 scale, and emotional states (positive and negative emotions) using the Scale of Positive and Negative Experience (SPANE). We found that while participants generally reported improvements across all measured outcomes, only participation in the Queensland Trust for Nature initiative, characterized by its extended duration and social interactions, demonstrated statistically significant enhancements in mental health and emotions after controlling for socio-economic confounders. These findings suggest that while short-term nature-based interventions can effectively alleviate anxiety and stress symptoms and boost emotions, significant changes in nature connection and depression may require more intensive interventions than what is available through typical citizen science experiences. We advocate for reframing nature-based initiatives as integral components of broader health-promoting strategies. By aligning citizen science efforts with health promotion frameworks, these initiatives can achieve greater impact and simultaneously advance scientific understanding, support conservation strategies while improving human health.
Impact of natural resources rents on green growth: evidence from G7 countries
Authors: Qian Jiangyunze , Chen Lai
Published: February 2025

Climate change has become a global issue in the 21st century due to the excessive use of non-renewable energy sources. To mitigate this issue, the world has been shifting towards green growth. For this purpose, researchers and policymakers are struggling to explore the factors that significantly impact green growth. Although several determinants of green growth have been investigated in the available literature, the impact of (dis)-aggregated natural resources rents (i.e., minerals rent, coal rent, oil rent, natural gas rent, and total natural resources rent) have been scantly investigated. To fill this gap, this study aims to examine the impact of coal rent, oil rent, minerals rent, natural gas rent, and total natural resources rent on the green growth in G7 countries. The findings from the panel ARDL approach elucidate that coal rent, natural gas rent, and total natural resources rent have a negative impact on green growth in the long-run. Further, oil rent has a positive impact, while minerals rent has an insignificant impact on green growth in the long-run. The study proposes several policy recommendations based on the findings.
Temporal lags and carbon-water coupling in the dry-hot valleys of southwest China over the past two decades
Authors: Wang Dawei , Jia Duni , Zhang Yao , Tao Xin , Han Feibing , Ma Yanbin , Guo Yu , Li Jinshan , Li Lili
Published: February 2025

Water use efficiency (WUE), as an important parameter of ecosystem carbon-water cycle, is an important index to assess vulnerability to extreme drought events. However, little was known about the corresponding cumulative and lagged responses of WUE to drought in the dry and hot valleys of Southwest China. This region is covered by alpine-valley landscapes, fragmented topographic features, Foehn Effect, where drought response mechanisms are not yet fully understood. This study analyzed the spatial-temporal variation of WUE from 2000 to 2020 in Binchuan (BC) and Yuanmou (YM) regions and the time-lag and -accumulation effects of 12 monthly self-calibrating Palmer Drought Index (scPDSI) on the WUE. Given the variability of vegetation types, land use/cover change data was used to investigate the variability of WUE between the two areas. Subsequently, the Pearson Correlation coefficient (Pearson, R) analysis, considering the influence of drought on time-lag and -accumulation effects, was used to analyze the response mechanism of water use efficiency to scPDSI in BC and YM comparatively. The results show that (1) From 2001 to 2020, BC’s average annual WUE was 2.59 gC m−2 mm−1, and YM’s was 2.84 gC·m−2·mm−1, with similar spatial distributions. (2) Over the past 2 decades, BC’s WUE increased steadily at a rate of 0.012 gC m-2 mm−1 a−1, while Yuanmou’s WUE grew at 0.0082 gC m-2 mm−1 a−1. (3) The lag response of WUE to drought is minimal in both regions, with BC’s cultivated land showing greater sensitivity to drought than YM. (4) The cumulative effect of drought on WUE across different land uses in both BC and YM is generally small, with the lowest sensitivity in forest land to drought.
Cervical cancer screening utilization among healthcare professionals in Ethiopia: systematic review and meta-analysis
Authors: Tizazu Michael Amera , Demsash Addisalem Workie , Mamo Tadesse , Kebede Tirusew Nigussie , Mihretie Abebe , Mamo Negash Kassa , Amogne Fetene Kassahun , Wubetu Abate Dargie
Published: February 2025

Background

Cancer of the cervix is the second most common cancer among women worldwide, with about over 660 000 new cases and approximately ninety-four percent of the 350 000 cervical cancer-related death happened in low- and middle-income countries. Effective screening initiatives are particularly crucial in preventing cervical cancer in women. Therefore, the purpose of this systematic literature review was to investigate the pooled prevalence of Ethiopian female healthcare professionals' cervical cancer screening utilization.

Methods

Published articles were searched from different major international databases (PubMed, Cochrane Library, Scopus, Web of Science, Since Direct, Google Scholar). Direct Google searches were used for additional sources mainly for gray and preprint studies. This review included studies that reported either the use of cervical cancer screening or cervical cancer screening predictors in Ethiopia. All published and unpublished studies through May/2024 and reported in the English language were retrieved to assess eligibility for inclusion in this review. The Newcastle-Ottawa Scale quality assessment tool was used to assess the quality of the included studies and Egger's test was used to assess the publication bias.

Results

In order to calculate the pooled prevalence of cervical cancer screening, 2,919 female healthcare professionals participated in the review. Articles were published from 2015 to 2024. The pooled Utilization of cervical cancer screening in Ethiopia, as determined by a meta-analysis of ten articles was 13.59% (95% CI: 7.53, 19.65).

Conclusion and recommendation

The estimated/pooled cervical cancer screening utilization was found to be lower than the World Health Organization recommendations as the estimator revealed in the meta-analysis. The low utilization of Cervical Cancer (CCa)screening practice despite they are healthcare professionals is a significant concern that can impact the broader efforts to combat cervical cancer. Based on the this reviews the authors recommend regular monitoring and evaluation of the CCa screening habits of healthcare professionals and the effectiveness of implemented interventions. It is necessary to explore the factors that enable or hinder CCa screening and address the issue through qualitative or mixed-method studies.
New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
Authors: Yang Chuanwei , Ren Xiaohui , Cui Yong , Jiang Haihui , Li Ming , Yu Kefu , Shen Shaoping , Li Mingxiao , Zhang Xiaokang , Zhao Xuzhe , Zhu Qinghui , Bu Xingyao , Lin Song
Published: February 2025

Primary central nervous system lymphoma (PCNSL) is non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Advances in molecular pathology studies for PCNSL have led to identifying new therapeutic targets and developing novel drugs. New therapeutic strategies, such as creating small molecule targeted agents, immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T (CAR-T) cell therapy, have brought new hope for patients with PCNSL, especially for R/R PCNSL. This review presents recent advances in the treatment of PCNSL, reviews and discusses the efficacy and challenges of targeted therapy and immunotherapy, and provides an outlook on the future development of PCNSL treatment strategies.
Predictors of severity and onset timing of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a retrospective analysis
Authors: Fang Qimei , Qian Yan , Xie Zhaolu , Zhao Hongqiong , Zheng Yang , Li Di
Published: February 2025

Objective

To identify predictors of all-grade, grade ≥ 3, and onset time of immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitors (ICIs) therapy.

Methods

This retrospective analysis included cancer patients treated with ICIs at Chongqing Medical University Second Affiliated Hospital from 2018 to 2024. Logistic regression and Cox regression analyses were used to identify predictors of all-grade and grade ≥ 3 irAEs and the time of irAE onset.

Results

Among the 3,795 patients analyzed, 1,101 (29.0%) developed all-grade irAEs, and 175 (4.6%) experienced grade ≥ 3 irAEs. Multivariate logistic regression revealed that female (OR = 1.37, p < 0.001), combination therapy (OR = 1.87, p < 0.001), pre-existing autoimmune diseases (AIDs) (OR = 5.15, p < 0.001), pre-existing cirrhosis (OR = 1.34, p = 0.001), antibiotic use during ICIs treatment (OR = 1.51, p < 0.001), and a higher baseline prognostic nutritional index (PNI) (OR = 1.23, p = 0.01) were significant predictors for the development of all-grade irAEs. The predictors for grade ≥ 3 irAEs included age ≥ 60 (OR = 1.49, p = 0.023) and pre-existing AIDs (OR = 2.09, p = 0.005), For the onset time, predictors included female (HR = 1.26, p = 0.001), combination therapy (HR = 1.80, p < 0.001), pre-existing AIDs (HR = 2.25, p < 0.001), and pre-existing infection (HR = 1.20, p = 0.008).

Conclusions

Females, combination therapy, pre-existing AIDs and cirrhosis, antibiotics, and a higher baseline PNI are associated with a higher risk of developing all-grade irAEs. Those aged ≥ 60 and with pre-existing AIDs face a higher risk of severe irAEs. Females, undergoing combination therapy, with pre-existing AIDs and infection generally experience a shorter time to irAEs onset. Multicentric prospective studies are warranted to validate these findings.
The genetics of hyper IgE syndromes
Authors: AlYafie Randa , Velayutham Dinesh , van Panhuys Nicholas , Jithesh Puthen Veettil
Published: February 2025

Hyper IgE syndromes (HIES) form a rare group of primary immunodeficiency disorders (PIDs) distinguished by persistent skin abscesses, dermatitis, allergies, and infections, in addition to their characteristic high serum IgE levels. Autosomal dominant (AD) and autosomal recessive (AR) genetic defects have been reported in HIES. From a clinical perspective, AD-HIES cases generally exhibit several non-immunologic features, including connective tissue, dental and skeletal abnormalities, whilst AR-HIES conditions have a higher incidence of neurologic complications and cutaneous viral infections. Genetic defects associated with HIES lead to impaired immune signaling, affecting pathways crucial for immune cell development, function, and immune response to pathogens/allergens. As a result, HIES patients are predisposed to recurrent bacterial and/or fungal infections, as well as atopic allergic responses. In many cases, the exact biological mechanisms responsible for the variations observed in the clinical phenotypes between the two inherited forms of HIES are still unclear. In this review, we describe the genetic basis of HIES with a distinction between the AR-HIES and AD-HIES forms, to better comprehend the different underlying molecular mechanisms, a distinction which is imperative for the accurate diagnosis, management, and development of targeted therapies for HIES patients.
AWT020: a novel fusion protein harnessing PD-1 blockade and selective IL-2 Cis-activation for enhanced anti-tumor immunity and diminished toxicity
Authors: Ye Fan , Huang Jianing , Cheng Xiaoli , Chen Shih Chieh , Huang Fang , Huang Wen-Chin , Hua Botong , Li Ella , Jiang Jenny , Lin Hanna , Siegel Matthew , Liao Eric , Wang Ji , Yue Bella , Shi Wenli , Xu Yanghua , Wang Xin , Wang Jiaming , Yan Yuyuan , He Honglin , Liu Eugene , Lu Binfeng , Zhong Ziyang
Published: February 2025

Background

The clinical success of the immune checkpoint inhibitor (ICI) targeting programmed cell death protein 1 (PD-1) has revolutionized cancer treatment. However, the full potential of PD-1 blockade therapy remains unrealized, as response rates are still low across many cancer types. Interleukin-2 (IL-2)-based immunotherapies hold promise, as they can stimulate robust T cell expansion and enhance effector function - activities that could synergize potently with PD-1 blockade. Yet, IL-2 therapies also carry a significant drawback: they can trigger severe systemic toxicities and induce immune suppression by expanding regulatory T cells.

Methods

To overcome the challenges of PD-1 blockade and IL-2 therapies while enhancing safety and efficacy, we have engineered a novel fusion protein, AWT020, combining a humanized anti-PD-1 nanobody and an engineered IL-2 mutein (IL-2c). The IL-2c component of AWT020 has been engineered to exhibit no binding to the IL-2 receptor alpha (IL-2Rα) subunit and attenuated affinity for the IL-2 receptor beta and gamma (IL-2Rβγ) complex, aiming to reduce systemic immune cell activation, thereby mitigating the severe toxicity often associated with IL-2 therapies. The anti-PD-1 antibody portion of AWT020 serves a dual purpose: it precisely delivers the IL-2c payload to tumor-infiltrating T cells while blocking the immune-inhibitory signals mediated by the PD-1 pathway.

Results

AWT020 showed significantly enhanced pSTAT5 signaling in PD-1 expressing cells and promoted the proliferation of activated T cells over natural killer (NK) cells. In preclinical studies using both anti-PD-1-sensitive and -resistant mouse tumor models, the mouse surrogate of AWT020 (mAWT020) demonstrated markedly enhanced anti-tumor efficacy compared to an anti-PD-1 antibody, IL-2, or the combination of an anti-PD-1 antibody and IL-2. In addition, the mAWT020 treatment was well-tolerated, with minimal signs of toxicity. Immune profiling revealed that mAWT020 preferentially expands CD8+ T cells within tumors, sparing peripheral T and NK cells. Notably, this selective tumoral T-cell stimulation enables potent tumor-specific T-cell responses, underscoring the molecule’s enhanced efficacy and safety.

Conclusion

The AWT020 fusion protein offers a promising novel immunotherapeutic strategy by integrating PD-1 blockade and IL-2 signaling, conferring enhanced anti-tumor activity with reduced toxicity.
Claudin-2 enhances human antibody-mediated complement-dependent cytotoxicity of porcine endothelial cells by modulating antibody binding and complement activation
Authors: Li Weilong , Yang Fang , Yang Dexin , Song Zhuoheng , Xu Zigan , Wu Jinmei , Li Yanmei , Chen Zixi , Chen Peishan , Yu Yeye , Xie Ting , Yang Cuishan , Zhou Liying , Luan Shaodong , Gao Hanchao
Published: February 2025

Background

Immune rejection represents a significant barrier to transplantation, especially in the context of xenotransplantation. Endothelial cells (ECs) derived from pigs serve as the initial barrier against the human immune system in xenotransplantation. Tight junction proteins are essential components of endothelial cell tight junctions; however, their role in xenotransplantation has been less thoroughly investigated. Claudin-2, a key tight junction protein, was investigated here for its role in human antibody-mediated complement-dependent cytotoxicity (CDC).

Methods

Using an in vitro model of human antibody-mediated CDC, we assessed the effect of Claudin-2 on porcine aortic endothelial cells (PAECs) and porcine iliac endothelial cells (PIECs). Claudin-2 expression was either knocked down or overexpressed in these cells. A flow cytometry assay was used to evaluate C3c, C9, and the C5b-9 deposition, as well as the extent of human IgM and IgG binding to PIECs. The mRNA levels of complement regulators (CD46, CD55, CD59, Factor H, Factor I) were quantified by real-time PCR.

Results

The loss of Claudin-2 protected PAECs and PIECs from human antibody-mediated CDC, while the overexpression of Claudin-2 enhanced the cytotoxicity in PAECs and PIECs within the same model. Unexpectedly, the loss or overexpression of Claudin-2 did not influence the mRNA expression levels of complement regulators (CD46, CD55, CD59, Factor H, and Factor I). Importantly, the loss of Claudin-2 significantly decreased the deposition of the C5b-9 complex, commonly referred to as the membrane attack complex (MAC), whereas the overexpression of Claudin-2 enhanced the deposition of the C5b-9 complex, indicating that Claudin-2 facilitates complement activation. Furthermore, the loss of Claudin-2 resulted in a decrease in the deposition of C3c and C9 on PIECs. Moreover, Claudin-2 enhanced human antibody binding to porcine ECs, as evidenced by increased IgG and IgM binding.

Conclusion

Our findings indicate that Claudin-2 enhances the cytotoxicity of porcine ECs through modulating antibody binding and complement activation. The deficient of Claudin-2 in genetically modified pigs is likely to protect porcine ECs and enhance xenograft survival in pig-to-human organ or tissue xenotransplantation.
Post-translational modifications in hepatocellular carcinoma: unlocking new frontiers in immunotherapy
Authors: Piao Yuexian , Zhai Naicui , Zhang Xiaoling , Zhao Wenjie , Li Min
Published: February 2025

Liver cancer, particularly hepatocellular carcinoma (HCC), is one of the most common and aggressive malignancies worldwide. Immunotherapy has shown promising results in treating HCC, but its efficacy is often limited by complex mechanisms of immune evasion. Post-translational modifications (PTMs) of proteins play a critical role in regulating the immune responses within the tumor microenvironment (TME). These modifications influence protein function, stability, and interactions, which either promote or inhibit immune cell activity in cancer. In this mini-review, we explore the diverse PTMs that impact immune evasion in liver cancer, including glycosylation, phosphorylation, acetylation, and ubiquitination. We focus on how these PTMs regulate key immune checkpoint molecules such as PD-L1, CTLA-4, and the TCR complex. Furthermore, we discuss the potential of targeting PTMs in combination with existing immunotherapies to enhance the effectiveness of treatment in HCC. Understanding the role of PTMs in immune regulation may lead to the development of novel therapeutic strategies to overcome resistance to immunotherapy in liver cancer.
Epilepsy in the onchocerciasis endemic area of Deim Zubeir, South Sudan: a household survey
Authors: Mamur Jurel Payii , Van Cutsem Gilles , Motto Sekonjo Juliano Hamid , Jada Stephen Raimon , Gerber Tatjana , Bol Yak Yak , Siewe Fodjo Joseph Nelson , Colebunders Robert
Published: February 2025

Background

High epilepsy prevalence and mortality has been reported in onchocerciasis-endemic areas with suboptimal elimination programs in South Sudan. In Deim Zubeir, an onchocerciasis-endemic area in Western Bahr El Ghazal state, demand for antiseizure medication is high, but epilepsy prevalence has never been investigated.

Methods

A two-step household survey was conducted in four locations in Deim Zubeir over two weeks in July 2023. Trained local community volunteers screened household members for epilepsy using four screening questions, assessed blindness, and inquired about family members’ deaths in the past three years. Participants with suspected epilepsy were referred to a medical doctor for confirmation of the diagnosis.

Results

A total of 7,807 individuals in 1,803 households participated in the survey; 180 (2.3%) had epilepsy and 146 (1.9%) were blind in at least one eye. The point prevalence of active epilepsy was 23.1 (95% confidence interval [CI] 20.0-26.6) per 1,000 persons. The median age of persons with epilepsy (PWE) was 25 (interquartile range [IQR] 20-31.5) years; median age at onset of seizures was 14 (IQR 9-19) years; 36.4% of PWE had siblings with a history of seizures; 5.3% were blind in at least one eye; 40.7% had burn lesions and 24.7% had skin lesions compatible with onchocerciasis; 55% met the criteria for onchocerciasis-associated epilepsy (OAE). The mortality rate of PWE was 182.4 per 100,000 person-years (95%CI 132.8-232.0) and the epilepsy case fatality rate was 64.1 (95% CI 47.2-80.9) per 1,000 PWE per year. PWE were six times more likely to die within one year than people without epilepsy. Their median age of death was 21.5 (IQR 16-34) years compared to 41 (IQR 7-60) years for people without epilepsy.

Conclusion

The prevalence of epilepsy and epilepsy-related mortality in Deim Zubeir is high, likely because of ongoing Onchocerca volvulus transmission. Strengthening the local onchocerciasis elimination program and ensuring consistent access to epilepsy care is urgently needed to prevent OAE and epilepsy-related mortality and morbidity. It is necessary to increase advocacy and funding to ensure early identification of epilepsy and uninterrupted, free access to antiseizure medication for PWE in this remote, impoverished area.
Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence
Authors: Farah Asmaa , Paul Pradipta , Khan Anfal Sher , Sarkar Aparajita , Laws Sa’ad , Chaari Ali
Published: February 2025

Introduction

The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

Methods

Through a comprehensive systematic review spanning key scientific databases—PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar—we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

Results

From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

Conclusion

Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments’ clinical efficacy and safety before widespread recommendations for clinical application.
How to create a faculty development program that transforms medical education according to actual institutional needs: evidence-based approach and experience at the University of Rijeka, Faculty of Medicine, Croatia
Authors: Pereza Nina , Hauser Goran , Dević Pavlić Sanja , Marić Ivana , Sotošek Vlatka , Grgasović Tina , Mršić-Pelčić Jasenka
Published: February 2025

Aim

Although previous studies demonstrated short, medium and long-term effectiveness of faculty development programs (FDP) for medical teachers, there is a lack of studies describing the methodology for creating a sustainable comprehensive FDP in medical education. We present the methodology for creating the “Modern and Practical Medical Education (MPME),” a comprehensive four-month educational FDP tailored to actual institutional needs, and the initial results of its implementation and transformation of medical education at the University of Rijeka, Faculty of Medicine, Croatia (EU).

Materials and methods

We conducted a multi-phase mixed-method cross-sectional study from July 2021 to June 2024 consisting of three steps: (1) construction of MPME FDP basic structure according to local/national priorities/specificities, literature and expertise, (2) a 360-degree current state analysis for adaptation of basic structure to actual institutional needs, and (3) analysis of the FDP education effectiveness. Step 2 included syllabi analyses and group interviews with 65 teachers’ at 8 departments (qualitative), as well as the analysis of medical students’ perspective using the “Medical students’ questionnaire” on 236 participants (quantitative), and 23 interviews with 8 participants using the “Medical students’ focus group” (qualitative). Step 3 included the quantitative analysis of 40 medical teachers’ self-assessments for 30 teachers’ competencies before and after MPME education using the “MPME questionnaire,” and qualitative analysis of measurable program outcomes.

Results

The MPME FDP consists of three major modules with seven courses, and is based on a tripartite flipped classroom model. The results of qualitative and quantitative 360-degree analysis identified common weak spots in teachers’ competencies, which were used for program development. Program effectiveness was demonstrated through a highly significant change in the self-assessment for all 30 teachers’ competencies before and after education (p < 0.001), and numerous measurable educational outcomes.

Conclusion

The creation of a comprehensive and sustainable FDP in medical education should be based on a three-step quantitative and qualitative process that includes the 360-degree analysis of actual institutional needs, and the effectiveness of the program education. This methodology has a highly significant positive effect on teachers’ competencies at the individual level, and creation of educational projects that transform medical education at the institutional level.