bluuebunny/crossref_metadata_2025 huggingface dataset:
Sperm swimming speed and morphology differ slightly among the three genetic morphs of ruff sandpiper (Calidris pugnax), but show no clear polymorphism
Authors: Bulla Martin , Küpper Clemens , Lank David B. , Albrechtová Jana , Loveland Jasmine L. , Martin Katrin , Teltscher Kim , Cragnolini Margherita , Lierz Michael , Albrecht Tomáš , Forstmeier Wolfgang , Kempenaers Bart
Published: December 2024

The ruff sandpiper (Calidris pugnax) is a lekking shorebird with three male morphs that differ remarkably in behavior, ornaments, size, and endocrinology. The morphs are determined by an autosomal inversion. Aggressive Independents evolved first, female-mimicking Faeders ~4 mil year ago when a short segment of a chromosome reversed in orientation, and semi-cooperative Satellites ~70,000 years ago through a recombination of the Independent and Faeder inversion-segment genotypes. Although the genetic differences between the morphs affect numerous phenotypic traits, it is unknown whether they also affect sperm traits. Here, we use a captive-bred population of ruffs to compare ruff sperm to that of other birds and compare sperm swimming speed and morphology among the morphs. Ruff sperm resembled those of passerines, but moved differently. Faeder sperm moved the slowest and had the longest midpiece. Independents’ sperm were neither the fastest nor the least variable, but had the shortest tail and midpiece. Although the midpiece contains the energy-producing mitochondria, its length was not associated with sperm swimming speed. Instead, two of three velocity metrics weakly positively correlated with head length (absolute and relative). We conclude that there is an indication of quantitative differences in sperm between morphs, but no clear sperm polymorphism.
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

Introduction

Vietnam’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).

Methods

The 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.

Results

A 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.

Discussion

In 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.
SOLA: dissecting dose-response patterns in multi-omics data using a semi-supervised workflow
Authors: Lai Wanxin , Song You , Tollefsen Knut Erik , Hvidsten Torgeir R.
Published: December 2024

An increasing number of ecotoxicological studies have used omics-data to understand the dose-response patterns of environmental stressors. However, very few have investigated complex non-monotonic dose-response patterns with multi-omics data. In the present study, we developed a novel semi-supervised network analysis workflow as an alternative to benchmark dose (BMD) modelling. We utilised a previously published multi-omics dataset generated from Daphnia magna after chronic gamma radiation exposure to obtain novel knowledge on the dose-dependent effects of radiation. Our approach combines 1) unsupervised co-expression network analysis to group genes with similar dose responses into modules; 2) supervised classification of these modules by relevant response patterns; 3) reconstruction of regulatory networks based on transcription factor binding motifs to reveal the mechanistic underpinning of the modules; 4) differential co-expression network analysis to compare the discovered modules across two datasets with different exposure periods; and 5) pathway enrichment analysis to integrate transcriptomics and metabolomics data. Our method unveiled both known and novel effects of gamma radiation, provide insight into shifts in responses from low to high dose rates, and can be used as an alternative approach for multi-omics dose-response analysis in future. The workflow SOLA (Semi-supervised Omics Landscape Analysis) is available at https://gitlab.com/wanxin.lai/SOLA.git.
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

Background

Pleural 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 methods

Patients 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.

Results

Higher 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.

Conclusions

Elevated 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

Background

The 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).

Methods

In 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.

Results

The 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.

Conclusions

The 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 Registration

https://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

Background

The 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.

Methods

A 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).

Results

We 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 < 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.

Conclusions

iMRS 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

Background

Gastric 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.

Methods

The 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.

Results

Through 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.

Conclusions

PCDHGA10 might be a potential prognostic marker and an immunological therapeutic target for GC.
Preparation of polymer hollow microsphere filled epoxy resin-based syntactic foam material and its performance analysis
Authors: Xue Wei , Feng Yi , Wang Jian , Fang Zumin , Shen Jiawen , Ma Yunfan , Wang Yueru , Liu Hechen , Li Le
Published: December 2024

To explore sound-absorbing and flame-retardant materials that meet the requirements for double-shielded and double-insulated Faraday cages, polymethyl methacrylate (PMMA) microspheres were incorporated into epoxy resin-based syntactic foam materials for testing and analysis. The addition of PMMA microspheres was found to enhance the electrical, mechanical, sound-absorbing, and flame-retardant properties of the syntactic foam, providing a potential reference for applications in high-voltage hall shielding and sound absorption. Syntactic foams with four concentrations of PMMA microspheres (0%, 0.5%, 1%, and 2%) were prepared. High-voltage breakdown testing, impedance tube testing for sound absorption coefficient, cone calorimetry for flame-retardant performance, and tensile and bending tests were conducted. Results showed that as the concentration of PMMA microspheres increased, improvements were observed in the tensile, bending, flame-retardant, and sound absorption properties of the syntactic foams, while breakdown strength decreased. These findings provide valuable insights into the application of syntactic foam materials in double-insulation, double-shielded Faraday cages.
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

Background

Vitamin 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.

Methods

This 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.

Results

In 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 <0.001. Notably, E-value analyses underscored the robustness of these results against potential unmeasured confounders.

Conclusion

This 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.
Could chronic opioid use be an additional risk of hepatic damage in patients with previous liver diseases, and what is the role of microbiome?
Authors: Tarantino Giovanni , Cataldi Mauro , Citro Vincenzo
Published: December 2024

Summary: Among illicit drugs, addiction from opioids and synthetic opioids is soaring in an unparalleled manner with its unacceptable amount of deaths. Apart from these extreme consequences, the liver toxicity is another important aspect that should be highlighted. Accordingly, the chronic use of these substances, of which fentanyl is the most frequently consumed, represents an additional risk of liver damage in patients with underlying chronic liver disease. These observations are drawn from various preclinical and clinical studies present in literature. Several downstream molecular events have been proposed, but recent pieces of research strengthen the hypothesis that dysbiosis of the gut microbiota is a solid mechanism inducing and worsening liver damage by both alcohol and illicit drugs. In this scenario, the gut flora modification ascribed to non-alcoholic fatty liver disease performs an additive role. Interestingly enough, HBV and HCV infections impact gut–liver axis. In the end, the authors tried to solicit the attention of operators on this major healthcare problem.
Asynchronous patterns in soil bacterial diversity and functional potentials along an alpine altitudinal gradient
Authors: Li Xianping , Li Teng , Li Huixin
Published: December 2024

Introduction

Altitudinal 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.

Methods

Here, 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.

Results

We 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.

Discussion

This 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.
Characteristics of the gut microbiota and the effect of Bifidobacterium in very early-onset inflammatory bowel disease patients with IL10RA mutations
Authors: Xu Xu , Gao Yuanqi , Xiao Yuan , Yu Yi , Huang Jiebin , Su Wen , Li Na , Xu Chundi , Gao Shenshen , Wang Xinqiong
Published: December 2024

Very early-onset inflammatory bowel disease (VEO-IBD) is a distinct subtype of inflammatory bowel disease (IBD) characterized by onset before the age of 6 years, and patients often exhibit more severe clinical features. Interleukin 10 receptor alpha (IL10RA) is a hotspot mutation in the Chinese population and is associated with a poor prognosis closely linked to the onset of IBD. However, limited knowledge exists regarding how the IL10RA mutation influences the host microbiota and its role in disease development. We employed 16S rRNA sequencing to conduct a comprehensive assessment of microbial changes in different types of IBD, employed database to thoroughly examine the influence of Bifidobacterium in IBD and to demonstrate a potential positive effect exerted by Bifidobacterium breve M16V (M16V) through a mouse model. The study demonstrated a significant reduction in the abundance and diversity of the gut microbiota among children with IL10RA mutations compared to those with late-onset pediatric IBD and nonmutated VEO-IBD. Furthermore, the analysis identified genera capable of distinguishing between various types of IBD, with the genus Bifidobacterium emerging as a potential standalone diagnostic indicator and Bifidobacterium may also be involved in related pathways that influence the progression of IBD, such as the biosynthesis of amino acids and inflammation-related pathways. This study corroborated the efficacy of Bifidobacterium in alleviating intestinal inflammation. The impact of IL10RA mutations on VEO-IBD may be mediated by alterations in microbes. M16V demonstrates efficacy in alleviating colitis and holds promise as a novel microbial therapy.
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

Background

In-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.

Methods

In 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.

Results

Our 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.

Conclusion

We 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

Background

Doxorubicin (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.

Methods

AutoDock 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.

Results

The 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.

Conclusion

This 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.
Effects of indium segregation and strain on near-infrared optical absorption in InGaN/GaN quantum wells
Authors: El Ghazi Haddou , En-nadir Redouane , Basyooni-M. Kabatas Mohamed A. , Ibrahim Jamal Eldin F. M. , Sali Ahmed
Published: December 2024

In this study, we present a novel numerical model that incorporates the effects of spontaneous and piezoelectric polarization-induced electric fields, along with multiple intersubband transitions, to investigate the optical absorption characteristics of InGaN/GaN strained single and double quantum well’s structures. Focusing on the role of Indium surface segregation (ISS) in polar QW structures, we examine its influence on intersubband transition-related optical absorption and the resulting spectral behavior. Specific structural configurations are designed to achieve four-energy-level with single and double quantum wells, optimized for three-color absorption within the near-infrared range. Our findings reveal that the combined impact of ISS and strain induces a notable red shift in the absorption spectra, with shifts varying significantly across different intersubband transitions. These findings underscore the potential of strained InGaN-based semiconductor compounds for developing advanced multi-color photonic devices, including near-infrared photodetectors and lasers, by harnessing their tunable optical properties.
Sturge–Weber syndrome: updates in translational neurology
Authors: Solomon Chase , Comi Anne
Published: December 2024

Sturge–Weber syndrome (SWS) is a rare congenital neurovascular disorder that initially presents with a facial port-wine birthmark (PWB) and most commonly associated with a R183Q somatic mosaic mutation in the gene GNAQ. This mutation is enriched in endothelial cells. Contrast-enhanced magnetic resonance imaging (MRI) diagnoses brain abnormalities including leptomeningeal vascular malformation, an enlarged choroid plexus, and abnormal cortical and subcortical blood vessels. Mouse SWS models identify dysregulated proteins important for abnormal vasculogenesis and blood brain barrier permeability. Recent clinical research has focused on early diagnosis, biomarker development, presymptomatic treatment, and development of novel treatment strategies. Prospective pilot clinical drug trials with cannabidiol (Epidiolex) or with sirolimus, an mTOR inhibitor, indicate possible reductions in seizure frequency and improved cognitive outcome. This review connects the most recent molecular research in SWS cell culture and animal models to developing new treatment methods and identifies future areas of research.
Alterations of fractional anisotropy and white matter integrity in irritable bowel syndrome: a systematic review and meta-analysis of diffusion tensor imaging studies
Authors: Asadi Anar Mahsa , Hassanpour Adeh Aydin , Peiravi Samira , Imani Porshokouh Alireza , Rezazadeh Shojaee Seyedeh Sara , Najafi Farnaz , Pishkari Yasamin , Rahimi Arash , Karami Shaghayegh
Published: December 2024

Background and aim

The neurological processes responsible for irritable bowel syndrome (IBS) pathophysiology and its clinical potentials are not fully understood. The current study aimed to examine white matter microstructural abnormalities and the reasons behind white matter impairment in individuals with irritable bowel syndrome by performing a meta-analysis of diffusion tensor imaging studies.

Methods

PubMed, Scopus and Web of Science were searched until April 2024. Chosen articles based on our defined eligibility criteria were extracted for the data relating to fractional anisotropy and brain connectivity. Webplot digitizer was used to extract digital data. We used the latest version of STATA(ver18) to meta-analyze the data. Quality assessment of studies was done using a critical appraisal tool. Egger’s test for minor study effects assessed the publication bias.

Results

543 IBS cases and 472 healthy controls were included in this study. The mean age of the case and control group was 35.2 ± 17.4 and 33.6 ± 15.8 (mean ± SD), respectively. There was no statistically significant difference in age between groups (p > 0.05). Analyzed Standard mean difference using a fixed model for Fractional anisotropy of regions of interest (ROI) associated with sensory processing, such as the thalamus, insula, primary somatosensory cortex, dorsal cingulum and the fornix in selected studies showcased decreased white matter interactivity in case group however this decrease was not statistically different [SMD −88, 95%CI (−1.32, −0.44), p > 0.05].

Conclusion

Further investigation is necessary to ascertain whether the modified structural connectivity mentioned in this study is a contributing factor to IBS, an outcome of the condition, a risk factor for it, or, more probably, a consequence of a mutually influential relationship between the changes observed in the white matter tract and IBS symptoms.
Prognostic importance of an indicator related to systemic inflammation and insulin resistance in patients with gastrointestinal cancer: a prospective study
Authors: Ruan Guo-Tian , Shi Jin-Yu , Xie Hai-Lun , Zhang He-Yang , Zhao Hong , Liu Xiao-Yue , Ge Yi-Zhong , Zhang Xiao-Wei , Yang Ming , Zhu Li-Chen , Shi Han-Ping
Published: December 2024

Background

Systemic inflammation (SI) and insulin resistance (IR) are correlated to the progression of gastrointestinal (GI) cancer. Therefore, this study aimed to analyze the potential clinical value of the C-reactive protein-triglyceride-glucose index (CTI) in relation to SI and IR in patients with GI cancer.

Methods

This prospective cohort study included patients with GI cancer. Patient data were collected from Fujian Cancer Hospital as an external validation cohort. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses were used to predict the efficacy and accuracy of CTI survival prediction. Multivariate survival analysis was performed to evaluate the potential prognostic value of the CTI. Multiple logistic regression was performed to evaluate the relationship between the CTI and 90-day and 180-day mortalities.

Results

We divided 1520 patients with GI cancer (mean age, 60.39 ± 11.3 years; male sex, 67%) into a training cohort and internal validation cohort; the external validation cohort included 476 patients. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses of all cohorts indicated that the CTI could reliably and accurately predict the short- and long-term survival outcomes of patients with GI cancer. Multivariate survival analysis showed that for each standard deviation increase in the CTI, the risk of death increased by 32%, 21%, and 40% in the training, internal validation, and external validation cohorts, respectively. A high CTI was correlated to worse survival in patients with GI cancer (training cohort, hazard ratio [HR]=1.67, 95% confidence interval [CI]=1.35–2.08; internal validation cohort, HR=1.51, 95% CI=1.07–2.14, and external validation cohort, HR=1.59, 95% CI=1.18–2.13). In different tumor subgroups, a high CTI predicted worse survival outcomes for upper GI cancer (HR=1.54, 95% CI=1.18–2.01) and lower GI cancer (HR=1.98, 95% CI=1.36–2.86). Multivariate logistic regression analysis showed that a high CTI was positively correlated with 90-day (odds ratio [OR]=3.25, 95% CI=1.75–6.23) and 180-day mortalities (OR=2.66, 95% CI=1.72–4.15).

Conclusions

The CTI is related to SI and IR and can predict the short- and long-term prognosis of patients with GI cancer. Evaluation of the CTI could provide clinicians with an effective tool for predicting the prognosis of patients with GI cancer.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=31813, identifier ChiCTR1800020329.
The efficacy and safety of neoadjuvant treatment with the PD-1 inhibitor for locally advanced colorectal cancer: a meta-analysis
Authors: Yu Yan , Huang Lin , Yan Rong , Jiang Min , Li Shuang-Jiao , Fan Wang-Dong
Published: December 2024

Objective

To systematically evaluate the efficacy and safety of PD-1 inhibitors in neoadjuvant therapy for locally advanced colorectal cancer (LACRC).

Method

Retrieved from PubMed, Embase, and the Cochrane Library, all relevant studies about PD-1 inhibitors for neoadjuvant treatment of LACRC were collected from inception to 31 December 2023. The efficacy was assessed by the rate of pathological complete response (PCR), clinical complete response (CCR), and major pathological response (MPR), and the safety was evaluated by the incidence of all adverse effects (TRAEs). Subgroup analysis was conducted by experimental design, types of PD-1 inhibitors, and disease types.

Result

A total of 803 patients were included in 21 studies. The results of the meta-analysis showed that the PCR rate of PD-1 inhibitors in the treatment of LACRC was 54% (95% CI: 43%–65%, P<0.05); the CCR of anti-PD-1 was 40% (95% CI: 26%–54%, P<0.05); the MPR was 66% (95% CI: 56%–76%, P<0.05); and the irAEs was 27% (95% CI: 17%–37%, P<0.05). Subgroup analysis showed that the PCRs in prospective studies and retrospective studies were 49% (95% CI: 32%–66%, P<0.05) and 57% (95% CI: 42%–73%, P<0.05), respectively. Among the 803 patients, 619 (77%) were diagnosed with rectal cancer (RC), and the PCR and MPR were 49% and 65%, respectively; 184 (23%) were diagnosed with colorectal cancer (CRC), and the PCR and MPR were both 67%. In our meta-analysis, types of PD-1 inhibitors, including sintilimab, toripalimab, camrelizumab, avelumab, pembrolizumab, and tislelizumab, and patients who received PD-1 inhibitors alone or in combination achieved good PCR rates.

Conclusion

Neoadjuvant therapy combined with a PD-1 inhibitor has a favorable PCR and relatively low incidences of irAEs for patients with LACRC, suggesting that this regimen including a PD-1 inhibitor is significantly effective and sufficiently safe.
Comprehensive genomic characterization of hematologic malignancies at a pediatric tertiary care center
Authors: Kebede Ann M. , Garfinkle Elizabeth A. R. , Mathew Mariam T. , Varga Elizabeth , Colace Susan I. , Wheeler Gregory , Kelly Benjamin J. , Schieffer Kathleen M. , Miller Katherine E. , Mardis Elaine R. , Cottrell Catherine E. , Potter Samara L.
Published: December 2024

Despite the increasing availability of comprehensive next generation sequencing (NGS), its role in characterizing pediatric hematologic malignancies remains undefined. We describe findings from comprehensive genomic profiling of hematologic malignancies at a pediatric tertiary care center. Patients enrolled on a translational research protocol to aid in cancer diagnosis, prognostication, treatment, and detection of cancer predisposition. Disease-involved samples underwent exome and RNA sequencing and analysis for single nucleotide variation, insertion/deletions, copy number alteration, structural variation, fusions, and gene expression. Twenty-eight patients with hematologic malignancies were nominated between 2018-2021. Eighteen individuals received both germline and somatic sequencing; two received germline sequencing only. Germline testing identified patients with cancer predisposition syndromes and non-cancer carrier states. Fifteen patients (15/18, 83%) had cancer-relevant somatic findings. Potential therapeutic targets were identified in seven patients (7/18, 38.9%); three (3/7, 42.9%) received targeted therapies and remain in remission an average of 47 months later.
Influence of zonular tension on molecular transport in the porcine ocular lens
Authors: Crews Morgan , Rich Wade , Reilly Matthew A.
Published: December 2024

Introduction

Accommodation is the process of changing the ocular lens’ refractive power and focal distance. This process involves application of biomechanical forces on the lens by the surrounding musculature. Previous studies have demonstrated that the lens epithelium demonstrates mechanotransduction and that tension influences its chemical activity. It is not yet known how these forces affect the structure and permeability of the lens. This study aimed to identify the influence of tension on molecular transport of dyes through the lens.

Methods

Paired porcine eyes were incubated in each of four dyes for three time periods with no stretch (null), static, or cyclic stretching using a bespoke mechanical lens stretcher. After incubation, the lenses were frozen and cryosectioned sagittally through the optic axis. Photographs of the stretched and unstretched lenses were compared and qualitatively assessed.

Results

None of the four dyes showed drastic stretch-induced differences in dye penetration depth. However, the dye neutral red showed dramatic stretch-induced changes in the dye uptake color behind lens anterior surfaces, with unstretched lenses appearing far more orange than their stretched counterparts. Three of four dyes showed notable differences between anterior and posterior diffusion patterns. One dye, methylene blue, demonstrated unexpected intensity in the lens nucleus compared to the lower intensity shown in the cortex, suggesting active transport rather than a linearly graded passive diffusion regardless of stretching condition.

Discussion

All this taken together suggests that lens transport is more complex than simple passive diffusion and that active transport of some molecules may be affected by stretching. Future work should assess the mechanisms of transport for the various dyes and attempt to explain the dye permeation patterns observed here, including the effects of stretching.
Mitigating neurodegenerative diseases: the protective influence of baicalin and baicalein through neuroinflammation regulation
Authors: Yang Rui , Wang Ranran , Xu Ajing , Zhang Jian , Ma Jing
Published: December 2024

Neurodegenerative diseases (NDDs) represent a category of serious illnesses characterized by the progressive deterioration of neuronal structure and function. The exploration of natural compounds as potential therapeutic agents has gained increasing attention in recent years owing to their wide range of pharmacological activities and minimal side effects. Baicalin (BAI) and baicalein (BE), polyphenolic flavonoids, derived from the root of Scutellaria baicalensis, evidently show potential in treating NDDs. This review provides an overview of the current understanding of the roles of BAI and BE in alleviating neuroinflammation, a pivotal pathological process implicated in various NDDs. Studies conducted prior to clinical trials have shown that BAI and BE exert protective effects on the nervous system in different animal models of NDDs. Furthermore, mechanistic studies indicate that BAI and BE exert anti-inflammatory effects by inhibiting pro-inflammatory cytokines, suppressing microglial activation, and regulating microglial phenotypes. These effects are mediated through the modulation of inflammatory signaling cascades, including Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), amp-activated protein kinase (AMPK), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, and nuclear factor erythroid 2-related factor 2 (Nrf2)/hemoglobin oxygenase-1 (HO-1). Overall, BAI and BE exhibit promising potential as natural compounds with anti-inflammatory properties and offer innovative therapeutic approaches for managing NDDs.
Muscle–brain crosstalk mediated by exercise-induced myokines - insights from experimental studies
Authors: Kostka Magdalena , Morys Julia , Małecki Andrzej , Nowacka-Chmielewska Marta
Published: December 2024

Over the past couple of decades, it has become apparent that skeletal muscles might be engaged in endocrine signaling, mostly as a result of exercise or physical activity in general. The importance of this phenomenon is currently studied in terms of the impact that exercise- or physical activity -induced signaling factors have, in the interaction of the “muscle-brain crosstalk.” So far, skeletal muscle-derived myokines were demonstrated to intercede in the connection between muscles and a plethora of various organs such as adipose tissue, liver, or pancreas. However, the exact mechanism of muscle-brain communication is yet to be determined. It is speculated that, in particular, brain-derived neurotrophic factor (BDNF), irisin, cathepsin B (CTSB), interleukin 6 (IL-6), and insulin-like growth factor-1 (IGF-1) partake in this crosstalk by promoting neuronal proliferation and synaptic plasticity, also resulting in improved cognition and ameliorated behavioral alterations. Researchers suggest that myokines might act directly on the brain parenchyma via crossing the blood-brain barrier (BBB). The following article reviews the information available regarding rodent studies on main myokines determined to cross the BBB, specifically addressing the association between exercise-induced myokine release and central nervous system (CNS) impairments. Although the hypothesis of skeletal muscles being critical sources of myokines seems promising, it should not be forgotten that the origin of these factors might vary, depending on the cell types engaged in their synthesis. Limited amount of research providing information on alterations in myokines expression in various organs at the same time, results in taking them only as circumstantial evidence on the way to determine the actual involvement of skeletal muscles in the overall state of homeostasis. The following article reviews the information available regarding rodent studies on main myokines determined to cross the BBB, specifically addressing the association between exercise-induced myokine release and CNS impairments.