bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020)
Authors: Kattenberg Johanna Helena , Mutsaers Mathijs , Nguyen Van Hong , Nguyen Thi Hong Ngoc , Umugwaneza Arlette , Lara-Escandell Maria , Nguyen Xuan Xa , Nguyen Thi Huong Binh , Rosanas-Urgell Anna 
Published: December 2024

IntroductionVietnam’s goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).MethodsThe custom targeted NGS amplicon sequencing assay, AmpliSeq Pf Vietnam v2, targeting drug resistance, population genetic- and other markers, was applied to detect genetic diversity and resistance profiles in samples from 8 provinces in Vietnam (n = 354), in a period of steep decline of incidence (2018–2020). Variants in 14 putative resistance genes, including P. falciparum Kelch 13 (PfK13) and P. falciparum chloroquine resistance transporter (Pfcrt), were analyzed and within-country parasite diversity was evaluated. Other targets included KEL1-lineage markers and diagnostic markers of Pfhrp2/3.ResultsA concerning level of DHA-PPQ resistance was detected. The C580Y mutation in PfK13 was found in nearly 80% of recent samples, a significant rise from previous data. Vietnam has experienced a significant challenge with the spread of DHA-PPQ resistant malaria parasites, particularly in the provinces of Binh Phuoc and Gia Lai. Resistance spread to high levels in Binh Thuan prior to the country-wide treatment policy change from DHA-PPQ to pyronadine-artesunate (PA). A complex picture of PPQ-resistance dynamics was observed, with an increase of PPQ-resistance associated Pfcrt mutations, indicating an evolutionary response to antimalarial pressure. Additionally, the compensatory mutation C258W in Pfcrt, which increases chloroquine (CQ) resistance while reversing PPQ resistance, is emerging in Gia Lai following the adoption of PA as the first-line treatment. This study found high levels of multidrug resistance, with over 70% of parasites in 6 out of 8 provinces showing significant sulfadoxine-pyrimethamine (SP) resistance and widespread chloroquine-resistant Pfcrt haplotypes. We also report an absence of P. falciparum histidine rich protein 2 and 3 (Pfhrp2/3) gene deletions, ensuring the continued reliability of HRP2/3-based rapid diagnostic tests. P. falciparum populations in Vietnam are becoming more isolated, with clonal populations showing high geographical clustering by province. The central highlands, particularly Gia Lai province, have the highest residual malaria burden but exhibit low diversity and clonal populations, likely due to the pressures from the antimalarial drugs and targeted national malaria control program (NMCP) efforts.DiscussionIn conclusion, examining a broad panel of full-length resistance genes and SNPs provided high-resolution insights into genetic diversity and resistance evolution in Vietnam, offering valuable information to inform local treatment and intervention strategies.
Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma
Authors: Farooqi Saima Jamil , Zhao Zhi , Öjlert Åsa Kristina , Thunold Solfrid , Juul Hedvig Vidarsdotter , Bjaanæs Maria Moksnes , Horndalsveen Henrik , Nymoen Hanne Marte Gjertsen , Helland Åslaug , Haakensen Vilde Drageset 
Published: December 2024

BackgroundPleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.Patients and methodsPatients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers.ResultsHigher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment.ConclusionsElevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.
Perioperative tislelizumab with four cycles of neoadjuvant chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: a phase 2 study
Authors: Zhou Na , Hua Yuwei , Ge Yuping , Wang Qiang , Wang Chenyu , He Jia , Zhao Luo , Yu Shuangni , Yan Junfang , Zhao Lin , Li Li , Bai Chunmei 
Published: December 2024

BackgroundThe application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC).MethodsIn this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy.ResultsThe study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte.ConclusionsThe combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC.Clinical Trial Registrationhttps://www.chictr.org.cn/, identifier ChiCTR2100043772.
Myeloid response evaluated by noninvasive CT imaging predicts post-surgical survival and immune checkpoint therapy benefits in patients with hepatocellular carcinoma
Authors: Peng Kangqiang , Zhang Xiao , Li Zhongliang , Wang Yongchun , Sun Hong-Wei , Zhao Wei , Pan Jielin , Zhang Xiao-Yang , Wu Xiaoling , Yu Xiangrong , Wu Chong , Weng Yulan , Lin Xiaowen , Liu Dingjie , Zhan Meixiao , Xu Jing , Zheng Limin , Zhang Yaojun , Lu Ligong 
Published: December 2024

BackgroundThe potential of preoperative CT in the assessment of myeloid immune response and its application in predicting prognosis and immune-checkpoint therapy outcomes in hepatocellular carcinoma (HCC) has not been explored.MethodsA total of 165 patients with pathological slides and multi-phase CT images were included to develop a radiomics signature for predicting the imaging-based myeloid response score (iMRS). Overall survival (OS) and recurrence-free survival (RFS) were assessed according to the iMRS risk group and validated in a surgical resection cohort (n = 98). The complementary advantage of iMRS incorporating significant clinicopathologic factors was investigated by the Cox proportional hazards analysis. Additionally, the iMRS in inferring the benefits of immune checkpoint therapy was explored in an immunotherapy cohort (n = 36).ResultsWe showed that AUCs of the optimal radiomics signature for iMRS were 0.941 [95% confidence interval (CI), 0.909–0.973] and 0.833 (0.798–0.868) in the training and test cohorts, respectively. High iMRS was associated with poor RFS and OS. The prognostic performance of the Clinical-iMRS nomogram was better than that of a single parameter (p &lt; 0.05), with a 1-, 3-, and 5-year C-index for RFS of 0.729, 0.709, and 0.713 in the training, test, and surgical resection cohorts, respectively. A high iMRS score predicted a higher proportion of objective response (vs. progressive disease or stable disease; odds ratio, 2.311; 95% CI, 1.144–4.672; p = 0.020; AUC, 0.718) in patients treated with anti-PD-1 and PD-L1.ConclusionsiMRS may provide a promising method for predicting local myeloid immune responses in HCC patients, inferring postsurgical prognosis, and evaluating benefits of immune checkpoint therapy.
Entamoeba histolytica-induced NETs are highly cytotoxic on hepatic and colonic cells due to serine proteases and myeloperoxidase activities
Authors: Jorge-Rosas Fabian , Díaz-Godínez César , García-Aguirre Samuel , Martínez-Calvillo Santiago , Carrero Julio César 
Published: December 2024

During intestinal and liver invasion by the protozoan parasite Entamoeba histolytica, extensive tissue destruction linked to large neutrophil infiltrates is observed. It has been proposed that microbicidal components of neutrophils are responsible for the damage, however, the mechanism by which they are released and act in the extracellular space remains unknown. In previous studies, we have shown that E. histolytica trophozoites induce NET formation, leading to the release of neutrophil granule content into extruded DNA. In this work, we evaluate the possible participation of NETs in the development of amoeba-associated pathology and analyze the contribution of anti-microbial components of the associated granules. E. histolytica-induced NETs were isolated and their effect on the viability and integrity of HCT 116 colonic and Hep G2 liver cultures were evaluated. The results showed that simple incubation of cell monolayers with purified NETs for 24 h resulted in cell detachment and death in a dose-dependent manner. The effect was thermolabile and correlated with the amount of DNA and protein present in NETs. Pretreatment of NETs with specific inhibitors of some microbicidal components suggested that serine proteases, are mostly responsible for the damage caused by NETs on HCT 116 cells, while the MPO activity was the most related to Hep G2 cells damage. Our study also points to a very important role of DNA as a scaffold for the activity of these proteins. We show evidence of the development of NETs in amoebic liver abscesses in hamsters as a preamble to evaluate their participation in tissue damage. In conclusion, these studies demonstrate that amoebic-induced NETs have potent cytotoxic effects on target cells and, therefore, may be responsible for the intense damage associated with tissue invasion by this parasite.
PCDHGA10 as a potential prognostic biomarker and correlated with immune infiltration in gastric cancer
Authors: Zhong Mingyang , Yu Zhuoqun , Wu Qianqian , Lu Bing , Sun PingPing , Zhang Xiaojing , Yang Lei , Wu Han 
Published: December 2024

BackgroundGastric cancer (GC) is one of the most common malignant tumors and is associated with poor prognosis. To improve the prognosis of GC patients, an effective immune-related prognostic biomarker is urgent. Here, we aim to explore the correlation between the expression of procalcitonin gamma subfamily A, 10 (PCDHGA10) and clinicopathological characteristics, especially its relation with tumor-infiltrating immune cells (TILs) in GC.MethodsThe differential mRNA expression of PCDHGA10 between GC tissues and normal gastric mucosa and prognostic potential were assessed from The Cancer Genome Atlas (TCGA). Then, based on tissue microarrays (TMAs) with multiplex immunohistochemistry (mIHC) from GC patients, we statistically assess the correlation between PCDHGA10 protein expression and the clinical profiles and prognosis of the patients. Additionally, with IHC and mIHC, we applied the machine-learning algorithms to evaluate the localization and expression levels of TILs and immune checkpoints in the tumor microenvironment. We analyzed the relationship between PCDHGA10 protein expression and TILs and immune checkpoints.ResultsThrough the database and TMA analysis, the expression of PCDHGA10 was significantly higher in GC tissues compared with normal tissues. High PCDHGA10 expression independently predicted poor prognosis in GC. Additionally, elevated PCDHGA10 expression was positively associated with the number of CD8+ T cells, CD68+ macrophages, Foxp3+ T cells, and CD4+ T cells in GC tissues and the stromal region. Besides, the expression of PCDHGA10 was positively correlated with immune checkpoints, including CTLA-4, LAG3, and PD-L1.ConclusionsPCDHGA10 might be a potential prognostic marker and an immunological therapeutic target for GC.
Vitamin D supplementation may be beneficial in improving the prognosis of patients with sepsis-associated acute kidney injury in the intensive care unit: a retrospective study
Authors: Sun Jie , Wang Yan , Wang Jue , Wu Hongwei , Xu Zhefeng , Niu Dongsheng 
Published: December 2024

BackgroundVitamin D, an essential fat-soluble micronutrient, exerts diverse physiological effects including the regulation of calcium ion homeostasis, modulation of immune response, and enhancement of resistance against infectious pathogens. Empirical investigations have elucidated an association between inadequate levels of vitamin D and adverse clinical outcomes in critically ill cohorts, with a noteworthy prevalence of vitamin D deficiency observed among patients afflicted with acute kidney injury (AKI). In the context of this retrospective inquiry, our aim was to assess the potential correlation between vitamin D supplementation administered during admission to the intensive care unit (ICU) and the improvement of outcomes specifically in cases of severe AKI.MethodsThis study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), a repository of ICU patient records from Beth Israel Deaconess Medical Center (BIDMC) in the United States. We focused on patients diagnosed with epsis-associated acute kidney injury (SA-AKI), dividing them into those who received vitamin D supplementation during their ICU admission and those who did not. Our primary analysis evaluated in-hospital mortality using various statistical methods, such as Kaplan–Meier survival curves, Cox proportional hazards regression models, and subgroup analyses. To enhance the robustness of our findings, we used propensity score matching (PSM) to reduce potential biases. Secondary outcomes included 28-day, 90-day mortality rates and norepinephrine-free days at 28 days.ResultsIn this investigation, a cohort of 11,896 individuals diagnosed with SA-AKI was studied. Among them, 2,724 patients received vitamin D supplementation (the vitamin D group) while 9,172 did not (the no-vitamin D group). Kaplan–Meier survival analysis indicated a significant difference in survival probabilities between the two cohorts. Upon adjusting for potential confounders using Cox regression modeling, a notably decreased risk of hospitalization and ICU mortality was observed in the vitamin D group compared to the no-vitamin D group, with an adjusted risk ratio for in-hospital mortality of 0.56 (95% CI: 0.5–0.63). These findings were consistent following PSM and subsequent adjustments for propensity score, pairwise algorithm (PA), and overlapping weights (OW) analyses, yielding hazard ratios ranging from 0.53 to 0.59, all with p-values &lt;0.001. Notably, E-value analyses underscored the robustness of these results against potential unmeasured confounders.ConclusionThis study suggests that vitamin D supplementation may be associated with a reduced in-hospital mortality rate among SA-AKI patients in the ICU. Furthermore, the 28-day, 90-day mortality rates and norepinephrine days were significantly reduced in the group receiving vitamin D supplementation.
Asynchronous patterns in soil bacterial diversity and functional potentials along an alpine altitudinal gradient
Authors: Li Xianping , Li Teng , Li Huixin 
Published: December 2024

IntroductionAltitudinal changes in soil bacterial diversity, composition, biotic interactions, and function are prevalent. However, the overall patterns and associations among these dimensions remain unclear, particularly in vulnerable alpine mountain ecosystems.MethodsHere, we investigated soil bacterial communities along a high-altitude gradient to elucidate patterns and associations in taxonomic and phylogenetic diversity, co-occurrence networks, and functional potentials.ResultsWe observed increasing altitudinal trends in bacterial richness and phylogenetic diversity, along with significant differences in taxonomic and phylogenetic composition across altitudes. The connectivity component of the co-occurrence network properties showed a negative association with altitude. We also observed high redundancy in functional potentials, resulting in insignificant variation in functional diversity along the altitudinal gradient. However, the strength of functional diversity varied based on the interaction between network connectivity and phylogenetic diversity. Additionally, functional dissimilarity was more closely associated with phylogenetic rather than taxonomic dissimilarity or differences in network properties, highlighting the role of phylogenetic lineages in functional redundancy.DiscussionThis study characterizes the altitudinal distribution of soil bacteria and explores their covariations, enhancing our understanding of soil bacterial diversity and functional potentials along altitudinal gradients and providing valuable insights for predicting community changes and improving alpine ecosystem conservation.
Effects of antibiotic growth promoter and its natural alternative on poultry cecum ecosystem: an integrated analysis of gut microbiota and host expression
Authors: Peng Chengyao , Ghanbari Mahdi , May Ali , Abeel Thomas 
Published: December 2024

BackgroundIn-feed antibiotic growth promoters (AGPs) have been a cornerstone in the livestock industry due to their role in enhancing growth and feed efficiency. However, concerns over antibiotic resistance have driven a shift away from AGPs toward natural alternatives. Despite the widespread use, the exact mechanisms of AGPs and alternatives are not fully understood. This necessitates holistic studies that investigate microbiota dynamics, host responses, and the interactions between these elements in the context of AGPs and alternative feed additives.MethodsIn this study, we conducted a multifaceted investigation of how Bacitracin, a common AGP, and a natural alternative impact both cecum microbiota and host expression in chickens. In addition to univariate and static differential abundance and expression analyses, we employed multivariate and time-course analyses to study this problem. To reveal host-microbe interactions, we assessed their overall correspondence and identified treatment-specific pairs of species and host expressed genes that showed significant correlations over time.ResultsOur analysis revealed that factors such as developmental age substantially impacted the cecum ecosystem more than feed additives. While feed additives significantly altered microbial compositions in the later stages, they did not significantly affect overall host gene expression. The differential expression indicated that with AGP administration, host transmembrane transporters and metallopeptidase activities were upregulated around day 21. Together with the modulated kininogen binding and phenylpyruvate tautomerase activity over time, this likely contributes to the growth-promoting effects of AGPs. The difference in responses between AGP and PFA supplementation suggests that these additives operate through distinct mechanisms.ConclusionWe investigated the impact of a common AGP and its natural alternative on poultry cecum ecosystem through an integrated analysis of both the microbiota and host responses. We found that AGP appears to enhance host nutrient utilization and modulate immune responses. The insights we gained are critical for identifying and developing effective AGP alternatives to advance sustainable livestock farming practices.
Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats
Authors: Alwaili Maha Abdullah , Abu-Almakarem Amal S. , Aljohani Salwa , Alkhodair Sahar Abdulrahman , Al-Bazi Maha M. , Eid Thamir M. , Alamri Jehan , Mobasher Maysa A. , K. Algarza Norah , A. Khayyat Arwa Ishaq , Alshaygy Luluah Saleh , El-Said Karim Samy 
Published: December 2024

BackgroundDoxorubicin (DOX) drugs used in cancer treatment can cause various adverse effects, including hepatotoxicity. Natural-derived constituents have shown promising effects in alleviating chemotherapy-induced toxicities. This study addressed the effect of Avenanthramides-C (AVN-C) treatment in rats with DOX-indued hepatotoxicity.MethodsAutoDock Vina was used for the molecular docking investigations. In silico toxicity prediction for AVN-C and DOX was performed using the Pro Tox-III server. Four groups of ten male Sprague-Dawley rats were created: Group 1 (Gp1) served as a negative control, Gp2 received an intraperitoneal (i.p.) injection of AVN-C (10 mg/kg), Gp3 received an i.p. dose of DOX (4 mg/kg) weekly for a month, and Gp4 received the same dose of DOX as G3 and AVN-C as G2. Histopathological, molecular, and biochemical analyses were conducted 1 month later.ResultsThe study showed that treatment with AVN-C significantly ameliorated DOX-induced hepatotoxicity in rats by restoring biochemical alterations, boosting antioxidant activity, reducing inflammation, and modulating the Akt/GSK-3β and Wnt-4/β-Catenin signaling pathways in male rats.ConclusionThis study is the first to demonstrate the therapeutic effects of AVN-C therapy on DOX-induced liver damage in male rats. Therefore, AVN-C could have a pronounced palliative effect on the hepatotoxicity caused by DOX treatment. These findings suggest that AVN-C could potentially alleviate the hepatotoxicity associated with DOX-based chemotherapy.