bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes and osteoporosis: a two-sample mendelian randomization study
Authors: Qu Yu-Dun , Zhu Zhao-Hua , Li Jia-Xuan , Zhang Wei , Chen Qi , Xia Chang-Liang , Ma Jun-Nan , Ou Shuan-Ji , Yang Yang , Qi Yong , Xu Chang-Peng 
Published: April 2024

Abstract
Background
The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design.

Methods
A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches.

Results
The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (β = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (β = 0.033, 95% CI: 0.003, 0.062), heel-BMD (β = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (β = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (β ranged from − 0.012 to 0.075).

Conclusions
Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.
Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial
Authors: Xu Li , Chen Jinzhang , Liu Chang , Song Xiaoling , Zhang Yanqiao , Zhao Haitao , Yan Sheng , Jia Weidong , Wu Zheng , Guo Yabing , Yang Jiayin , Gong Wei , Ma Yue , Yang Xiaobo , Gao Zhenzhen , Zhang Nu , Zheng Xin , Li Mengyu , Su Dan , Chen Minshan 
Published: April 2024

Abstract
Background
Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC.

Methods
In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon’s two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy.

Results
Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients.

Conclusions
Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC.

Trial registration
ClinicalTrials.gov (NCT 04401800).
Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients
Authors: Sornsamdang Gaidganok , Satapornpong Patompong , Jinda Pimonpan , Jantararoungtong Thawinee , Koomdee Napatrupron , Tempark Therdpong , Klaewsongkram Jettanong , Rerkpattanapipat Ticha , Rerknimitr Pawinee , Tuchinda Papapit , Chularojanamontri Leena , Tovanabutra Napatra , Chanprapaph Kumutnart , Disphanurat Wareeporn , Chakkavittumrong Panlop , Srisuttiyakorn Chutika , Srinoulprasert Yuttana , John Shobana , Biswas Mohitosh , Sukasem Chonlaphat 
Published: April 2024

Abstract
Background
Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. Methods: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls.

Results
Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2–266.8; P = 1.9 × 10− 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3–670.5 and p-value = 1.7 × 10− 27).

Conclusions
Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.
Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach
Authors: Beg Anam , Parveen Rafat , Fouad Hassan , Yahia M. E. , Hassanein Azza S. 
Published: April 2024

AbstractTarget-driven cancer therapy is a notable advancement in precision oncology that has been accompanied by substantial medical accomplishments. Ovarian cancer is a highly frequent neoplasm in women and exhibits significant genomic and clinical heterogeneity. In a previous publication, we presented an extensive bioinformatics study aimed at identifying specific biomarkers associated with ovarian cancer. The findings of the network analysis indicate the presence of a cluster of nine dysregulated hub genes that exhibited significance in the underlying biological processes and contributed to the initiation of ovarian cancer. Here in this research article, we are proceeding our previous research by taking all hub genes into consideration for further analysis. GEPIA2 was used to identify patterns in the expression of critical genes. The KM plotter analysis indicated that the out of all genes 5 genes are statistically significant. The cBioPortal platform was further used to investigate the frequency of genetic mutations across the board and how they affected the survival of the patients. Maximum mutation was reported by ELAVL2. In order to discover viable therapeutic candidates after competitive inhibition of ELAVL2 with small molecular drug complex, high throughput screening and docking studies were used. Five compounds were identified. Overall, our results suggest that the ELAV-like protein 2-ZINC03830554 complex was relatively stable during the molecular dynamic simulation. The five compounds that have been found can also be further examined as potential therapeutic possibilities. The combined findings suggest that ELAVL2, together with their genetic changes, can be investigated in therapeutic interventions for precision oncology, leveraging early diagnostics and target-driven therapy.
Loss of AMPK activity induces organelle dysfunction and oxidative stress during oocyte aging
Authors: Hu Lin-Lin , Liao Mei-Hua , Liu Ya-Xi , Xing Chun-Hua , Nong Lan-Lan , Yang Feng-Lian , Sun Shao-Chen 
Published: April 2024

Abstract
Background
Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging.

Results
In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed.

Conclusions
Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.
NRT1.1B mediates rice plant growth and soil microbial diversity under different nitrogen conditions
Authors: Ju Yawen , Jia Yanyan , Cheng Baoshan , Wang Di , Gu Dalu , Jing Wenjiang , Zhang Hao , Chen Xinhong , Li Gang 
Published: April 2024

AbstractInteractions between microorganisms and plants can stimulate plant growth and promote nitrogen cycling. Nitrogen fertilizers are routinely used in agriculture to improve crop growth and yield; however, poor use efficiency impairs the optimal utilization of such fertilizers. Differences in the microbial diversity and plant growth of rice soil under different nitrogen application conditions and the expression of nitrogen-use efficiency-related genes have not been previously investigated. Therefore, this study investigates how nitrogen application and nitrogen-use efficiency-related gene NRT1.1B expression affect the soil microbial diversity and growth indices of two rice varieties, Huaidao 5 and Xinhuai 5. In total, 103,463 and 98,427 operational taxonomic units were detected in the soils of the Huaidao 5 and Xinhuai 5 rice varieties, respectively. The Shannon and Simpson indices initially increased and then decreased, whereas the Chao and abundance-based coverage estimator indices decreased after the application of nitrogen fertilizer. Nitrogen fertilization also reduced soil bacterial diversity and richness, as indicated by the reduced abundances of Azotobacter recorded in the soils of both rice varieties. Nitrogen application initially increased and then decreased the grain number per panicle, yield per plant, root, stem, and leaf nitrogen, total nitrogen content, glutamine synthetase, nitrate reductase, urease, and root activities of both varieties. Plant height showed positive linear trends in response to nitrogen application, whereas thousand-grain weights showed a negative trend. Our findings may be used to optimize nitrogen fertilizer use for rice cultivation and develop crop-variety-specific strategies for nitrogen fertilizer application.
Extracorporeal membrane oxygenation technology for adults: an evidence mapping based on systematic reviews
Authors: Xie Kai , Jing Hui , Guan Shengnan , Kong Xinxin , Ji Wenshuai , Du Chen , Jia Mingyan , Wang Haifeng 
Published: April 2024

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial.

Methods
We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy.

Results
A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was “Critically low” to “Moderate”. One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics.

Conclusions
There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.
Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting
Authors: Huang Huageng , Zhang Wei , Deng Xinyi , Huang He , Wang Zhao , Hong Huangming , Lin Tongyu 
Published: April 2024

AbstractPeripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3–4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies.
Associations between glucocorticoids and habitat selection reflect daily and seasonal energy requirements
Authors: Newediuk Levi , Mastromonaco Gabriela F. , Vander Wal Eric 
Published: April 2024

Abstract
Background
Glucocorticoids are often associated with stressful environments, but they are also thought to drive the best strategies to improve fitness in stressful environments. Glucocorticoids improve fitness in part by regulating foraging behaviours in response to daily and seasonal energy requirements. However, many studies demonstrating relationships between foraging behaviour and glucocorticoids are experimental, and few observational studies conducted under natural conditions have tested whether changing glucocorticoid levels are related to daily and seasonal changes in energy requirements.

Methods
We integrated glucocorticoids into habitat selection models to test for relationships between foraging behaviour and glucocorticoid levels in elk (Cervus canadensis) as their daily and seasonal energy requirements changed. Using integrated step selection analysis, we tested whether elevated glucocorticoid levels were related to foraging habitat selection on a daily scale and whether that relationship became stronger during lactation, one of the greatest seasonal periods of energy requirement for female mammals.

Results
We found stronger selection of foraging habitat by female elk with elevated glucocorticoids (eß = 1.44 95% CI 1.01, 2.04). We found no difference in overall glucocorticoid levels after calving, nor a significant change in the relationship between glucocorticoids and foraging habitat selection at the time of calving. However, we found a gradual increase in the relationship between glucocorticoids and habitat selection by female elk as their calves grew over the next few months (eß = 1.01, 95% CI 1.00, 1.02), suggesting a potentially stronger physiological effect of glucocorticoids for elk with increasing energy requirements.

Conclusions
We suggest glucocorticoid-integrated habitat selection models demonstrate the role of glucocorticoids in regulating foraging responses to daily and seasonal energy requirements. Ultimately, this integration will help elucidate the implications of elevated glucocorticoids under natural conditions.
Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction
Authors: Gong Ting , Liu You-Tan , Fan Jie 
Published: April 2024

AbstractSepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.
Severity of COVID-19 infection in patients with COVID-19 combined with diabetes
Authors: Lu Dan , Liu Yuhong , Ma Pengcheng , Hou Rui , Wang Jin 
Published: April 2024

Abstract
Purpose
This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes.

Methods
Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the ‘good blood glucose control’ group and the ‘poor blood glucose control’ group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors.

Results
The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12.

Conclusion
Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.
Strengthening from dislocation restructuring and local climb at platelet linear complexions in Al-Cu alloys
Authors: Garg Pulkit , Gianola Daniel S. , Rupert Timothy J. 
Published: April 2024

AbstractStress-driven segregation at dislocations can lead to structural transitions between different linear complexion states. In this work, we examine how platelet array linear complexions affect dislocation motion and quantify the associated strengthening effect in Al-Cu alloys using atomistic simulations. The presence of platelet complexions leads to the faceting of the dislocations, with nanoscale segments climbing upwards along the platelet growth direction, resulting in a complex configuration that restricts subsequent dislocation motion. Upon deformation, the leading partial dislocation must climb down from the platelet complexions first, followed by a similar sequence at the trailing partial dislocation, in order to overcome the precipitates and commence plastic slip. The dislocation depinning mechanism of linear complexions is strikingly different from traditional precipitation-strengthened alloys, where dislocations overcome obstacles by either shearing through or looping around obstacles. The critical shear stress required to unpin dislocations from platelet complexions is found to be inversely proportional to precipitate spacing, which includes not just the open space (as observed in Orowan bowing) but also the region along the platelet particle where climb occurs. Thus, linear complexions provide a new way to modify dislocation structure directly and improve the mechanical properties of metal alloys.