bluuebunny/crossref_metadata_2025 huggingface dataset:
USP28 protects development of inflammation in mouse intestine by regulating STAT5 phosphorylation and IL22 production in T lymphocytes
Authors: Le Menn Gwenaëlle , Pikkarainen Keela , Mennerich Daniela , Miroszewska Dominika , Kietzmann Thomas , Chen Zhi
Published: July 2024

Introduction

Ubiquitin-specific proteases (USPs), a large subset of more than 50 deubiquitinase proteins, have recently emerged as promising targets in cancer. However, their role in immune cell regulation, particularly in T cell activation, differentiation, and effector functions, remains largely unexplored.

Methods

We utilized a USP28 knockout mouse line to study the effect of USP28 on T cell activation and function, and its role in intestinal inflammation using the dextran sulfate sodium (DSS)-induced colitis model and a series of in vitro assays.

Results

Our results show that USP28 exerts protective effects in acute intestinal inflammation. Mechanistically, USP28 knockout mice (USP28-/-) exhibited an increase in total T cells mainly due to an increased CD8+ T cell content. Additionally, USP28 deficiency resulted in early defects in T cell activation and functional changes. Specifically, we observed a reduced expression of IL17 and an increase in inducible regulatory T (iTreg) suppressive functions. Importantly, activated T cells lacking USP28 showed increased STAT5 phosphorylation. Consistent with these findings, these mice exhibited increased susceptibility to acute DSS-induced intestinal inflammation, accompanied by elevated IL22 cytokine levels.

Conclusions

Our findings demonstrate that USP28 is essential for T cell functionality and protects mice from acute DSS-induced colitis by regulating STAT5 signaling and IL22 production. As a T cell regulator, USP28 plays a crucial role in immune responses and intestinal health.
Complete remission in a patient with sinonasal squamous cell carcinoma receiving neoadjuvant tislelizumab plus chemotherapy: a case report
Authors: Chen Fang , Zhang Hongzheng , Li Yonghe , Liang Tingfeng , Zhang Tao
Published: July 2024

Sinonasal squamous cell carcinoma (SNSCC) is the most common, high-aggressive sinonasal malignancies that have remained relatively stable poor outcomes over the past decade. As a first-line treatment for SNSCC, surgery plus adjuvant radiotherapy is recommended. However, complete surgical resection may not be appropriate due to the proximity of the nasal cavity and sinuses to key structures such as orbit or intracranial. Currently, immune checkpoint inhibitors (ICIs) have been established as one of the first-line therapies for many solid tumors with unresectable stage. However, evidence on the efficacy of ICIs in sinonasal malignancy is scarce and no ICIs are approved for use in SNSCC up to day. In this report, we report a case of a 64-year-old man with SNSCC treated by multi-protocol exploration. The patient achieved pathological complete response (pCR) after receiving two cycles of Docetaxel and cisplatin combined with tislelizumab. To the best of our knowledge, this is the first case of SNSCC treated with tislelizumab that achieved pCR. This case offers real-world evidence that chemotherapy plus immunotherapy is a promising treatment for SNSCC.
Early prediction of spontaneous preterm birth before 34 gestational weeks based on a combination of inflammation-associated plasma proteins
Authors: Svenvik Maria , Raffetseder Johanna , Brudin Lars , Berg Göran , Hellberg Sandra , Blomberg Marie , Jenmalm Maria C. , Ernerudh Jan
Published: July 2024

Background

In order to identify and possibly offer prophylactic treatment to women at risk for preterm birth (PTB), novel prediction models for PTB are needed. Our objective was to utilize high-sensitive plasma protein profiling to investigate whether early prediction of spontaneous PTB (sPTB) before 34 gestational weeks (gw) was possible in a low-risk population.

Methods

A case-control study was conducted on 46 women with sPTB before 34 gw and 46 women with normal pregnancies and term deliveries. Prospectively collected plasma sampled at gw 11 (range 7-16) and gw 25 (range 23-30) was analyzed with a high-sensitivity Proximity Extension Assay for levels of 177 inflammation-associated proteins, and statistically processed with multivariate logistic regression analysis.

Results

In the first trimester, higher levels of hepatocyte growth factor (HGF) were associated with sPTB <34 gw (OR 1.49 (1.03-2.15)). In the second trimester, higher levels of interleukin (IL)-10 (OR 2.15 (1.18-3.92)), IL-6 (OR 2.59 (1.34-4.99)), and the receptor activator of nuclear factor κB (RANK) (OR 2.18 (1.26-3.77)) were associated with sPTB <34 gw. The area under the curve for the prediction models including these proteins was 0.653 (0.534-0.759) in the first trimester and 0.854 (0.754-0.925) in the second trimester.

Conclusion

A combination of inflammation-associated plasma proteins from the second trimester of pregnancy showed a good predictive ability regarding sPTB before 34 gw, suggesting it could be a valuable supplement for the assessment of the clinical risk of sPTB. However, although a high number (n=177) of plasma proteins were analyzed with a high-sensitivity method, the prediction of sPTB in the first trimester remains elusive.
Case report: Complete response after transcatheter arterial chemoembolization combined with donafenib plus tislelizumab therapy for hepatocellular carcinoma with main trunk portal vein tumor thrombus in a patient coinfected with HIV and HBV
Authors: Xiao Xuhua , Fu Haixiao , Qin Huixia , Xu Longkuan , Gu Jing , Zhang Zhan , Ya Houxiang , Jiang Kaiwen , Jian Zhiyuan , Li Shuqun
Published: July 2024

Background

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5–67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus.

Case presentation

A 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography.

Conclusion

We first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.
The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications
Authors: Yang Kai , Wang Xi , Pan Hanyu , Wang Xinqing , Hu Yunhan , Yao Yihe , Zhao Xinyue , Sun Taolei
Published: July 2024

AIM2, a cytosolic innate immune receptor, has the capability to recognize double-stranded DNA (dsDNA). This paper delineates the structural features of AIM2 and its mechanisms of activation, emphasizing its capacity to detect cytosolic DNA and initiate inflammasome assembly. Additionally, we explore the diverse functions of AIM2 in different cells. Insights into AIM2-mediated neuroinflammation provide a foundation for investigating novel therapeutic strategies targeting AIM2 signaling pathways. Furthermore, we present a comprehensive review of the roles of AIM2 in neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Finally, we discuss its therapeutic implications. In conclusion, a profound understanding of AIM2 in neurodegenerative diseases may facilitate the development of effective interventions to mitigate neuronal damage and slow disease progression.
Reduced seagrass resilience due to environmental and anthropogenic effects may lead to future die-off events in Florida Bay
Authors: de Fouw Jimmy , Madden Christopher J. , Furman Bradley T. , Hall Margaret O. , Verstijnen Yvon , Holthuijsen Sander , Frankovich Thomas A. , Strazisar Theresa , Blaha Michelle , Van Der Heide Tjisse
Published: July 2024

Coastal systems often depend on foundation species such as seagrasses that are supported by self-facilitation. Seagrass meadows, however, are threatened worldwide due to climate change and local human impact, disrupting self-facilitation leading to system instability. Florida Bay is a large seagrass dominated coastal ecosystem that suffered from multiple seagrass mortality events over the last half century driven by hypoxia, high water temperatures, hypersalinity, and high biological oxygen demand. These conditions reduce the amount of photosynthetically-derived oxygen in the plant causing sulphide intrusion into meristematic tissues. Using a bay-wide sampling design and long-term monitoring trends of seagrass condition, we investigated the current state of the meadows, sediment characteristics (e.g., organic matter, sulphide, nutrients) and discuss how climate stressors interact with plant and sediment oxygen dynamics. Our survey revealed that at sites where seagrass had been previously denuded by die-off, the dominant seagrass Thalassia testudinum had not recovered, while the pioneering seagrass Halodule wrightii recolonized the impacted areas. Organic matter and sulphide levels were higher at the impacted sites, apparently a persistent characteristic of the formerly dense T. testudinum meadows in central and western Florida Bay. These sediment conditions promote sulphide intrusion of T. testudinum belowground tissue under anoxic conditions. Plant oxidation initially buffers sulphide intrusion, but disruption of this oxidation mechanism due to changing environmental conditions results in widespread mortality and seagrass community collapse. Climate change cannot be fully mitigated by local management, however, attempts can be made to control critical salinity and oxygen levels by increasing freshwater input, reducing hypersalinity and aiming to keep the internal seagrass oxidation feedback intact. Our study shows that the Florida Bay seagrass ecosystem is still recovering four years post die-off and continues to be susceptible to future climate change and system degradation.
Listen to your heart: a critical analysis of popular cardiology podcasts
Authors: Kamalanathan Harish , Hains Lewis , Bacchi Stephen , Martin Wrivu N. , Zaka Ammar , Slattery Flynn , Kovoor Joshua G. , Gupta Aashray K. , Psaltis Peter , Kovoor Pramesh
Published: July 2024

Purpose

Podcasts are an increasingly popular medium for medical education in the field of cardiology. However, evidence suggests that the quality of the information presented can be variable. The aim of our study was to assess the quality of the most popular cardiology podcasts on existing podcast streaming services, using tools designed to grade online medical education.

Results

We analyzed the five most recent episodes from 28 different popular cardiology podcasts as of 20th of September, 2022 using the validated rMETRIQ and JAMA scoring tools. The median podcast length was 20 min and most episodes were hosted by professors, subspecialty discussants or consultant physicians (87.14%). Although most episodes had only essential content (85%), only a small proportion of episodes provided detailed references (12.9%), explicitly identified conflicts of interest (30.7%), described a review process (13.6%), or provided a robust discussion of the podcast's content (13.6%). We observed no consistent relationship between episode length, seniority of host or seniority of guest speaker with rMETRIQ or JAMA scores.

Conclusions

Cardiology podcasts are a valuable remote learning tool for clinicians. However, the reliability, relevance, and transparency of information provided on cardiology podcasts varies widely. Streamlined standards for evaluation are needed to improve podcast quality.
Evaluation of the blended public health empowerment program-basic field epidemiology in the Eastern Mediterranean Region
Authors: Alsouri Ruba Kamal , Khader Yousef , Bashier Haitham , Amiri Mirwais , Morsy Sara Abdelkarim , Abbas Zainab Naseer , Farah Zeina Elias , Al Nsour Mohannad
Published: July 2024

Introduction

The COVID-19 pandemic encouraged the shift toward technology-based learning globally, impacting education systems profoundly. In response to this emerging need, the Eastern Mediterranean Public Health Network (EMPHNET) adapted its Public Health Empowerment Program-Basic Field Epidemiology (PHEP-BFE) to a Blended Learning Model. This study evaluates the Blended PHEP-BFE program in Iraq, Egypt, and Lebanon, focusing on participant reactions and learning outcomes.

Methods

A descriptive evaluation was conducted, aligned with the first two levels of Kirkpatrick's model. Online questionnaires were administered to participants and facilitators through EMPHNET's Learning Management System (LMS). Qualitative and quantitative data were analyzed to assess program effectiveness, satisfaction, and challenges.

Results

A total of 138 PHEP-BFE participants (119 (86.2%) males and 19 (13.8%) females) from Iraq (n = 61), Egypt (n = 66), and Lebanon (n = 11) responded to the questionnaire. The majority of the participants (96.4%) reported that they were satisfied with PHEP-BFE. Notably, 77.5% of participants rated the blended learning program as very good or excellent, 18.1% rated it good, and 3.6% found it average, with a minimal 0.7% expressing dissatisfaction. The majority of participants agreed that the blended PHEP-BFE enhanced their capacity to conduct, review and monitor surveillance data (95.7%), perform descriptive data analysis (94.2%), effectively communicate information with agency staff and the local community (95.7%), write summaries of surveillance findings or outbreak investigations (95.7%), use MS Excel to enter, analyze, and display public health surveillance data (91.3%), prepare and administer an oral presentation for fieldwork (94.9%), and increase their knowledge of fundamental field epidemiology (94.9%). The participants responded positively to the program's content, training duration, learning platform, facilitators and mentors, and fieldwork.

Conclusion

The study showcases the success of the blended PHEP-BFE in diverse contexts, emphasizing positive participant reactions and improved competencies. The evaluation underscores the program's success in advancing public health training in the EMR. Blended learning models prove promising for future FETP initiatives, contributing valuable insights to public health workforce development. Positive outcomes and identified challenges, provide a roadmap for continuous improvement.
Efficacy and safety of variceal embolization for primary prophylaxis in cirrhosis patients with challenges in standard treatments: preliminary results
Authors: Tie Jun , Yuan Xulong , Zhu Ying , Li Kai , Gou Xiaoyuan , Han Na , Niu Jing , Xu Jiao , Wang Wenlan , Shi Yongquan
Published: July 2024

Objectives

Nonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments.

Methods

The study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications.

Results

The procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients).

Conclusion

Variceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.
Atopic dermatitis in Ethiopian children: a multicenter study of clinical severity, characteristics, and sociodemographic factors
Authors: Kelbore Abraham Getachew , Enbiale Wendemagegn , van Wyk Jacqueline M. , Mosam Anisa
Published: July 2024

Background

Atopic dermatitis (AD) is a chronic relapsing, pruritic, inflammatory skin disease. Assessing the characteristics and risk factors of severe AD is central to healthcare workers’ understanding and subsequent education of patients for the most optimal outcomes. The clinical characteristics are known to vary depending on populations and regions. AD has been well-documented in the global North in mainly Caucasian populations, while very few studies have been conducted on African patients residing in Africa. This study assessed the clinical characteristics, severity, and sociodemographic factors of children with AD in Southern Ethiopia.

Methods

A hospital-based cross-sectional study was conducted among 461 children and their caregivers in four randomly selected hospitals in Southern Ethiopia from October 2022 to September 2023. A systematic sampling technique was used to enroll study participants. Clinical profile and sociodemographic data were collected by trained data collectors. The Scoring Atopic Dermatitis (SCORAD) index tool was used. The descriptive analysis was performed to characterize study participants. Univariate and ordinary logistic regression were used to identify factors associated with the SCORAD index score. The OR with 95% was used to show the strength of association, and a p-value of <0.05 was used to declare the level of significance.

Result

Out of 461 AD-diagnosed children, 212 (46%) were girls and 249 (54%) were boys. In the sample of pediatric patients, 149 (32.3%) exhibited mild AD, 231 (46.2%) presented with moderate, and 99 (21.5%) showed signs and symptoms of severe AD. All patients had itching. Dryness of skin, excoriation, and erythema, followed by lichenification, were the most observed signs. In the ordinary logistic regression model, age onset of the disease [AOR 95% CI 1.95 (1.3–2.94)], sex of caregiver or family [AOR 95% CI 0.61 (0.41–0.90)], family atopy history [AOR 95% CI 0.64 (0.44–0.93)], mother education status [95% CI 2.45 (1.1–5.47)], and use of herbal medication [AOR 95% CI 0.50 (0.33–0.79)] were significantly associated with the severity of AD.

Conclusion

In this study, 68% of children were found to have moderate-to-severe AD. Early onset, maternal education, familial atopy history, sex of caregiver, and use of herbal medication were independent predictors of severe AD in children. We recommend further investigation into these variables for their potential to serve as markers to assess the severity of AD and improve the care and management of children with AD in Ethiopia.
The gut microbial differences between pre-released and wild red deer: Firmicutes abundance may affect wild adaptation after release
Authors: Guo Jinhao , Li Zheng , Jin Yongchao , Sun Yue , Wang Binying , Liu Xinxin , Yuan Ziao , Zhang Weiqi , Zhang Changzhi , Zhang Minghai
Published: July 2024

Insufficient density of red deer has affected the stability of forest ecosystems and the recovery of large carnivores (represented by Amur tiger). Conservation translocations from captivity to the wild has become an important way to restore the red deer populations. However, the difference in gut microbes between pre-release and wild red deer may affect the feeding adaptability of red deer after release. In this study, we clarified the differences in gut microbes between pre-released and wild red deer and screened the key gut microbes of the red deer involved in feeding by using metagenomic sequencing and feeding analysis. The results showed that the microbial difference between pre-released and wild red deer was mainly related to Firmicutes represented by Eubacteriales and Clostridia, and Firmicutes abundance in pre-released red deer (68.23%) was significantly lower than that of wild red deer (74.91%, p < 0.05). The expression of microbial metabolic pathways in pre-released red deer were significantly lower than those in wild red deer (p < 0.05), including carbohydrate metabolism, amino acid metabolism, glycan biosynthesis and metabolism, etc. The combinations of Firmicutes were significantly positively correlated with the intake of plant fiber and carbohydrate (p < 0.05), and were key microbes to help red deer deal with wild plant resources. Additionally, the combinations of Firmicutes represented by Eubacteriales and Clostridia lacking in pre-released red deer contributed the most to expression of microbial metabolic pathways (importance > 1), showing a significant positive correlation (p < 0.05). This study indicates that high abundance of Firmicutes is an important guarantee for red deer to adapt to the wild feeding environment, which provides critical implications for the recovery of red deer populations and the protection of endangered ungulates.
Combined analysis of the microbiome and metabolome to reveal the characteristics of saliva from different diets: a comparison among vegans, seafood-based omnivores, and red meat (beef and lamb) omnivores
Authors: Sun Shiyu , Zhang Huiqiong , Ye Linying , Huang Litao , Du Jieyu , Liang Xiaomin , Zhang Xiaofeng , Chen Jiaxing , Jiang Yingping , Chen Ling
Published: July 2024

Introduction

Revealing individual characteristics is supportive for identifying individuals in forensic crime. As saliva is one of the most common biological samples used in crime scenes, it is important to make full use of the rich individual information contained in saliva. The aim of this study was to explore the application of the microbiome in forensic science by analysing differences in the salivary microbiome and metabolome of healthy individuals with different dietary habits.

Methods

We performed 16S rDNA sequencing analysis based on oral saliva samples collected from 12 vegetarians, 12 seafood omnivores and 12 beef and lamb omnivores. Non-targeted metabolomics analyses were also performed based on saliva samples from healthy individuals.

Results

The results showed that the dominant flora of vegetarians was dominated by Neisseria (belonging to the phylum Proteobacteria), while seafood omnivores and beef and lamb omnivores were dominated by Streptococcus (belonging to the phylum Firmicutes). NDMS-based and cluster analyses showed that vegetarian dieters were significantly differentiated from meat dieters (seafood omnivores and beef and lamb omnivores), which may be related to the fact that high-fiber diets can create a different salivary flora structure. Variants were also detected in salivary metabolic pathways, including positive correlations with Lipid metabolism, Amino acid metabolism, Carbohydrate metabolism, and Nucleotide metabolism in vegetarians, and correlations in seafood omnivores. In order to select salivary microorganisms and metabolic markers that can distinguish different dietary profiles, a random forest classifier model was constructed in this study, and the results showed that individuals with different dietary profiles could be successfully distinguished based on the core genera and metabolites such as Streptococcus, Histidinyl-Valine.

Conclusion

Our study provides a supportive basis for the application of salivary polyomics in order to reveal the dietary characteristics of individuals for forensic investigation and crime solving.
Comparative evaluation of 16S rRNA primer pairs in identifying nitrifying guilds in soils under long-term organic fertilization and water management
Authors: Zhou Xue , Liu Xiaoyin , Liu Meiyu , Liu Weixuan , Xu Junzeng , Li Yawei
Published: July 2024

Compared with 454 sequencing technology, short-read sequencing (e.g., Illumina) technology generates sequences of high accuracy, but limited length (<500 bp). Such a limitation can prove that studying a target gene using a large amplicon (>500 bp) is challenging. The ammonia monooxygenase subunit A (amoA) gene of ammonia-oxidizing archaea (AOA), which plays a crucial part in the nitrification process, is such a gene. By providing a full overview of the community of a functional microbial guild, 16S ribosomal ribonucleic acid (rRNA) gene sequencing could overcome this problem. However, it remains unclear how 16S rRNA primer selection influences the quantification of relative abundance and the identification of community composition of nitrifiers, especially AOA. In the present study, a comparison was made between the performance of primer pairs 338F-806R, 515F-806R, and 515F-907R to a shotgun metagenome approach. The structure of nitrifier communities subjected to different long-term organic matter amendment and water management protocols was assessed. Overall, we observed higher Chao1 richness diversity of soil total bacteria by using 515F-806R compared to 338F-806R and 515F-907R, while higher Pielou’s evenness diversity was observed by using 515F-806R and 515F-907R compared to 338F-806R. The studied primer pairs revealed different performances on the relative abundance of Thaumarchaeota, AOB, and NOB. The Thaumarchaeota 16S rRNA sequence was rarely detected using 338F-806R, while the relative abundances of Thaumarchaeota detected using 515F-806R were higher than those detected by using 515F-907R. AOB showed higher proportions in the 338F-806R and 515F-907R data, than in 515F-806R data. Different primers pairs showed significant change in relative proportion of NOB. Nonetheless, we found consistent patterns of the phylotype distribution of nitrifiers in different treatments. Nitrosopumilales (NP) and Nitrososphaerales (NS) clades were the dominant members of the AOA community in soils subject to controlled irrigation, whereas Ca. Nitrosotaleales (NT) and NS clades dominated the AOA community in soils subject to flooding irrigation. Nitrospira lineage II was the dominant NOB phylotype in all samples. Overall, ideal 16S rRNA primer pairs were identified for the analysis of nitrifier communities. Moreover, NP and NT clades of AOA might have distinct environmental adaptation strategies under different irrigation treatments.
Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization
Authors: Lu Yi , Cai Xiaobing , Shi Baohua , Gong Haitao
Published: July 2024

Objective

Osteoporosis, characterized by reduced bone density and heightened fracture risk, is influenced by genetic and environmental factors. This study investigates the interplay between gut microbiota, plasma metabolomics, and osteoporosis, identifying potential causal relationships mediated by plasma metabolites.

Methods

Utilizing aggregated genome-wide association studies (GWAS) data, a comprehensive two-sample Mendelian Randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1,400 plasma metabolites, and osteoporosis indicators. Causal relationships between gut microbiota, plasma metabolites, and osteoporosis were explored.

Results

The MR analyses revealed ten gut microbiota taxa associated with osteoporosis, with five taxa positively linked to increased risk and five negatively associated. Additionally, 96 plasma metabolites exhibited potential causal relationships with osteoporosis, with 49 showing positive associations and 47 displaying negative associations. Mediation analyses identified six causal pathways connecting gut microbiota to osteoporosis through ten mediating relationships involving seven distinct plasma metabolites, two of which demonstrated suppression effects.

Conclusion

This study provides suggestive evidence of genetic correlations and causal links between gut microbiota, plasma metabolites, and osteoporosis. The findings underscore the complex, multifactorial nature of osteoporosis and suggest the potential of gut microbiota and plasma metabolite profiles as biomarkers or therapeutic targets in the management of osteoporosis.
The importance of brain mapping for rehabilitation in birth nonprogressive neuromuscular diseases
Authors: Tolmacheva Aleksandra , Agranovich Olga , Blagovechtchenski Evgeny
Published: July 2024

While motor mapping has been extensively studied in acquired motor conditions, a lack has been observed in terms of research on neurological disorders present since birth, with damage to the spinal cord and peripheral nerves (hence, defined in this study as nonprogressive neuromuscular diseases). Despite an injury at the level below the brain, the subsequent changes in the motor system involve cortical reorganization. In the scientific community, the need for a comprehensive approach targeting the brain is increasingly recognized for greater motor recovery in these patients. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are the most utilized techniques for motor mapping. The knowledge obtained through motor mapping may be used to develop effective individual neuromodulation therapy that helps in functional motor recovery. This brief review compares the results of the brain mapping of a few existing studies in individuals with nonprogressive motor disorders of nonbrain origin present at birth to the brain mapping of individuals with similar acquired motor conditions. The review reveals some particular features in terms of central adaptation in individuals with birth conditions compared to their acquired counterparts, such as the nonsomatotopic presentation of involved muscles in the sensorimotor cortex and nonadjacent cortical areas. This topic is undoubtedly intriguing, justifying further research in the field. This review also discusses the benefits these patients can obtain from neuromodulation therapy addressed to the central nervous system and the importance of individual neurophysiological assessment in designing rehabilitation therapy for children with birth motor disorders.
NFAT3-FasL axis synchronously regulates apoptosis and necroptosis in murine cochlear outer hair cells after noise trauma
Authors: Wang Wenlun , Yu Lisheng , Li Shichang , Han Lin , Zheng Hongwei
Published: July 2024

Existing studies have indicated that noise induces apoptosis and necroptosis in cochlear outer hair cells (OHCs). However, the role of the extrinsic cell death pathway, initiated by death ligands in the cochlea, remains unknown. In this study, we hypothesized that noise could induce the NFAT3/FasL axis-mediated extrinsic death pathway in the cochlea. We found that NFAT3/FasL signaling was silent in normal OHCs. Noise exposure induced apoptosis and necroptosis in OHCs with specifically high FasL expression. Multiplex immunofluorescence staining revealed that NFAT3 nuclear translocation and FasL upregulation were colocalized in the apoptotic and necroptotic OHCs following noise trauma. Administration of FK506 or 11R-vivit (an specific NFAT inhibitor) blocked NFAT3 nuclear translocation, inhibited FasL expression, mitigated apoptosis and necroptosis, and protected against noise-induced hearing loss (NIHL). Finally, FasL knockdown by delivering siRNA intratympanically attenuated apoptosis and necroptosis in OHCs and alleviated NIHL, confirming the role of FasL in OHC death. Collectively, our study demonstrates that the NFAT3/FasL axis mediates noise-induced extrinsic death pathway in OHCs, leading to their apoptosis and necroptosis.
Case report: Metastatic BRAF V600E–mutated adult Wilms’ tumor with robust response to BRAF/MEK inhibitor therapy
Authors: Kroll Matthew R. , Au Cherry , Slostad Jessica , Christ Trevor N. , Papas Sam G. , Tan Alan
Published: July 2024

Nephroblastoma or Wilms’ tumor (WT) is the most common pediatric renal malignancy but rare in adults. Treatment protocols for adults are typically extrapolated from pediatric guidelines, but there are no standard guidelines for adults due to the rarity of the disease. However, next-generation sequencing has led to new therapeutic options for adult WT patients. We present the first case to our knowledge of a recurrent adult WT treated with dual BRAF/MEK–targeted therapy, which showed initial robust clinical response and was well tolerated.
Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis
Authors: O’Reilly David , O’Leary Caroline L. , Reilly Aislinn , Teo Min Yuen , O’Kane Grainne , Hendriks Lizza , Bennett Kathleen , Naidoo Jarushka
Published: July 2024

The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% – 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI ‘run-in’ to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI ‘run-in’ was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.
Nuclear receptors in ovarian cancer: changing paradigms in cancer therapeutics
Authors: Sajeev Anjana , BharathwajChetty Bandari , Manickasamy Mukesh Kumar , Alqahtani Mohammed S. , Abbas Mohamed , Shakibaei Mehdi , Sethi Gautam , Ma Zhaowu , Kunnumakkara Ajaikumar B.
Published: July 2024

Ovarian cancer (OVC) is one of the most common causes of cancer-related deaths in women worldwide. Despite advancements in detection and therapy, the prognosis of OVC remains poor due to late diagnosis and the lack of effective therapeutic options at advanced stages. Therefore, a better understanding of the biology underlying OVC is essential for the development of effective strategies for early detection and targeted therapies. Nuclear receptors (NRs) are a superfamily of 48 transcription factors that, upon binding to their specific ligand, play a vital role in regulating various cellular processes such as growth, development, metabolism, and homeostasis. Accumulating evidence from several studies has shown that their aberrant expression is associated with multiple human diseases. Numerous NRs have shown significant effects in the development of various cancers, including OVC. This review summarizes the recent findings on the role of NRs in OVC, as well as their potential as prognostic and therapeutic markers. Further, the basic structure and signaling mechanism of NRs have also been discussed briefly. Moreover, this review highlights their cellular and molecular mechanisms in chemoresistance and chemosensitization. Further, the clinical trials targeting NRs for the treatment of OVC have also been discussed.
Superior cuproptotic efficacy of diethyldithiocarbamate-Cu4O3 nanoparticles over diethyldithiocarbamate-Cu2O nanoparticles in metastatic hepatocellular carcinoma
Authors: Abu-Serie Marwa M. , Barakat Assem , Ramadan Sherif , Habashy Noha Hassan
Published: July 2024

Metastatic hepatocellular carcinoma (HC) is a serious health concern. The stemness of cancer stem cells (CSCs) is a key driver for HC tumorigenesis, apoptotic resistance, and metastasis, and functional mitochondria are critical for its maintenance. Cuproptosis is Cu-dependent non-apoptotic pathway (mitochondrial dysfunction) via inactivating mitochondrial enzymes (pyruvate dehydrogenase “PDH” and succinate dehydrogenase “SDH”). To effectively treat metastatic HC, it is necessary to induce selective cuproptosis (for halting cancer stemness genes) with selective oxidative imbalance (for increasing cell susceptibility to cuproptosis and inducing non-CSCs death). Herein, two types of Cu oxide nanoparticles (Cu4O3 “C(I + II)” NPs and Cu2O “C(I)” NPs) were used in combination with diethyldithiocarbamate (DD, an aldehyde dehydrogenase “ALDH” inhibitor) for comparative anti-HC investigation. DC(I + II) NPs exhibited higher cytotoxicity, mitochondrial membrane potential, and anti-migration impact than DC(I) NPs in the treated human HC cells (HepG2 and/or Huh7). Moreover, DC(I + II) NPs were more effective than DC(I) NPs in the treatment of HC mouse groups. This was mediated via higher selective accumulation of DC(I + II) NPs in only tumor tissues and oxidant activity, causing stronger selective inhibition of mitochondrial enzymes (PDH, SDH, and ALDH2) than DC(I)NPs. This effect resulted in more suppression of tumor and metastasis markers as well as stemness gene expressions in DC(I + II) NPs-treated HC mice. In addition, both nanocomplexes normalized liver function and hematological parameters. The computational analysis found that DC(I + II) showed higher binding affinity to most of the tested enzymes. Accordingly, DC(I + II) NPs represent a highly effective therapeutic formulation compared to DC(I) NPs for metastatic HC.
Association between amoxicillin administration and outcomes in critically ill patients with acute kidney injury
Authors: Luo Xinyao , Zhou Weijian , Wan Dingyuan , Peng Jing , Liao Ruoxi , Su Baihai
Published: July 2024

Purpose

This study assessed the effect of amoxicillin on outcomes in intensive care unit (ICU) patients with acute kidney injury (AKI), focusing on mortality rates and acute kidney disease (AKD) occurrence.

Materials and Methods

We conducted a retrospective cohort analysis utilizing data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The study included intensive care unit patients diagnosed with AKI to assess the effects of post-admission amoxicillin administration on 30-day and 90-day mortality rates and acute kidney disease incidence. We employed Cox proportional hazards models, propensity score matching, and inverse probability of treatment weighting to control for potential confounders.

Results

Among 24,650 AKI patients, 676 (2.7%) received amoxicillin. The results indicated significantly lower mortality rates at 30 days (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.42–0.69) and 90 days (HR 0.64, 95% CI 0.52–0.77) in the amoxicillin group compared to non-recipients. Additionally, amoxicillin administration was associated with a reduced incidence of AKD (HR 0.49, 95% CI 0.36–0.65) but resulted in a modestly increased length of hospital stay (mean difference [MD] 1.95 days, 95% CI 1.15–2.75). A dose‒response relationship was evident, with higher doses (>875 mg) further decreasing mortality rates. Subgroup analysis revealed consistent benefits across most patient groups.

Conclusion

Amoxicillin administration following ICU admission in patients with AKI was associated with improved survival rates and a lower incidence of AKD, highlighting its potential as a therapeutic measure for AKI management.
Advancing vaccine development against Opisthorchis viverrini: A synergistic integration of omics technologies and advanced computational tools
Authors: Kafle Alok , Ojha Suvash Chandra
Published: July 2024

Graphical Abstract

Sincere gratitude to Prof. Jennifer Keiser for generously granting permission for the use of tegument picture in this graphical abstract.
Effectiveness of traditional herbal Kampo medicine Goreisan on chronic subdural hematoma recurrence: a meta-analysis
Authors: Yang Zhenyu , Zeng Yuecheng , Hu Jinyang , Huang Xin , Zhang Haiquan , Liu Yang
Published: July 2024

Objectives: Our objective was to compare the effectiveness of Traditional Chinese herbal Kampo medicine Goreisan in improving recurrence in patients with chronic subdural hematoma (CSDH).

Methods: Eligible randomized controlled trials prospective trials, and retrospective cohort studies were systematically identified through searches of PubMed, Cochrane Library, and CNKI from inception to March 2024. Following the application of predetermined inclusion and exclusion criteria to screen the available studies, main outcome measures were rigorously extracted. RevMan v5.4 software was utilized to evaluate the overall recurrence rate, employing a random-effects model to calculate pooled odds ratios with the Mantel-Haenszel estimation method. Inter-study heterogeneity was assessed using the Cochran Q (Chi-square) test and I2 statistics. Funnel plots were used to evaluate publication bias.

Results: Among the 48 articles initially screened for citation, eight were ultimately selected for inclusion in the study. The results of our network meta-analysis indicate that patients with newly diagnosed Chronic subdural hematoma experienced a significantly reduced recurrence rate when treated with Goreisan compared to standard neurosurgical treatment (OR: 0.72; 95% CI 0.61–0.86; p = 0.00003). There was no statistically significant difference in the incidence rates of complications, including general fatigue, allergic reactions, hepatic dysfunction, and interstitial pneumonia (OR: 7.21; 95% CI 0.37–141.29; p = 0.19).

Conclusion: Traditional medicine Goreisan was effective in reducing CDSH recurrence rates. For clinical treatment, it provides a high level of evidence-based medicine. It is also necessary to conduct multicenter randomized controlled trials with dose adjustments to determine whether Goreisan interventions improve neurological function or prognosis.
Evaluation of the effect of agroclimatic variables on the probability and timing of olive fruit fly attack
Authors: Rondoni Gabriele , Mattioli Elisabetta , Giannuzzi Vito Antonio , Chierici Elena , Betti Andrea , Natale Gaetano , Petacchi Ruggero , Famiani Franco , Natale Antonio , Conti Eric
Published: July 2024

Agroclimatic variables may affect insect and plant phenology, with unpredictable effects on pest populations and crop losses. Bactrocera oleae Rossi (Diptera: Tephritidae) is a specific pest of Olea europaea plants that can cause annual economic losses of more than one billion US dollars in the Mediterranean region. In this study, we aimed at understanding the effect of olive tree phenology and other agroclimatic variables on B. oleae infestation dynamics in the Umbria region (Central Italy). Analyses were carried out on B. oleae infestation data collected in 79 olive groves during a 7-year period (from 2015 to 2021). In July–August, B. oleae infestation (1% attack) was negatively affected by altitude and spring mean daily temperatures and positively by higher winter mean daily temperatures and olive tree cumulative degree days. In September–October, infestation was negatively affected by a positive soil water balance and high spring temperatures. High altitude and cumulative plant degree days were related to delayed attacks. In contrast, high winter and spring temperatures accelerated them. Our results could be helpful for the development of predictive models and for increasing the reliability of decision support systems currently used in olive orchards.
The rising use of cognitive enhancement drugs and predictors of use during COVID-19: findings from a cross-sectional survey of students and university staff in the UK
Authors: Tully Jamie L. , Bridge Oliver , Rennie Joseph , Krecké Joy , Stevens Tobias
Published: July 2024

Background

The use of psychoactive substances to increase cognitive performance while studying has been termed ‘pharmacological cognitive enhancement’ (PCE). In previous years, several large-scale national surveys have focused on their use by students at university, including drug types, prevalence rates, and predictive factors. The recent coronavirus pandemic brought about widespread structural changes for UK universities, as students were forced to adapt to home-based learning and in many cases reduced academic support. No study has yet focused primarily on the impact of pandemic social restrictions on PCE in students and academic staff, and whether personality and demographic factors reveal user profiles that predict use during the pandemic period.

Method

A convenience sample of 736 UK students and staff aged 18–54 (M = 22.2, SD = 5.2) completed a cross-sectional survey assessing PCE prevalence rates, polydrug use, perceived effects, academic self-efficacy and personality during the first year of social restrictions (March 2020 – February 2021) compared with the previous year (March 2019 – February 2020).

Results

There was a significant self-reported rise in the use of all drug types (all ps < 0.001) during social restrictions, particularly with Modafinil (+42%), nutraceuticals (+30.2%) and microdose LSD (+22.2%). Respondents also indicated stronger PCE effects for all substances, except alcohol, in comparison to the previous year. Polydrug use with modafinil and other prescription stimulants increased the most during social restrictions. Personality factors and gender identity reliably predicted PCE use and lower agreeableness was often the strongest predictor, followed by identifying as male and lower conscientiousness. Academic self-efficacy and student/academic staff status were not consistent predictors.

Conclusion

This is the first survey of UK students to investigate PCE during coronavirus social restrictions and to assess predictive factors. Findings reveal a rise in PCE use and polydrug use which we suggest is because of increased pressures on students created by the lockdown and reduced access to university resources.