bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of recombinant H5 vaccines delivered in ovo or day of age in commercial broilers against the 2015 U.S. H5N2 clade 2.3.4.4c highly pathogenic avian Influenza virus
Authors: Kapczynski Darrell R. , Chrzastek Klaudia , Shanmugasundaram Revathi , Zsak Aniko , Segovia Karen , Sellers Holly , Suarez David L. 
Published: December 2023

Abstract
Background
Avian influenza is a highly contagious, agriculturally relevant disease that can severely affect the poultry industry and food supply. Eurasian-origin H5Nx highly pathogenic avian influenza viruses (HPAIV) (clade 2.3.4.4) have been circulating globally in wild birds with spill over into commercial poultry operations. The negative impact to commercial poultry renewed interest in the development of vaccines against these viruses to control outbreaks in the U.S.

Methods
The efficacy of three recombinant H5 vaccines delivered in ovo or day of age were evaluated in commercial broilers challenged with the 2015 U.S. H5N2 clade 2.3.4.4c HPAIV. The recombinant vaccines included an alphavirus RNA particle vaccine (RP-H5), an inactivated reverse genetics-derived (RG-H5) and recombinant HVT vaccine (rHVT-AI) expressing H5 hemagglutinin (HA) genes. In the first experiment, in ovo vaccination with RP-H5 or rHVT-AI was tested against HPAI challenge at 3 or 6 weeks of age. In a second experiment, broilers were vaccinated at 1 day of age with a dose of either 107 or 108 RP-H5, or RG-H5 (512 HA units (HAU) per dose).

Results
In experiment one, the RP-H5 provided no protection following in ovo application, and shedding titers were similar to sham vaccinated birds. However, when the RP-H5 was delivered in ovo with a boost at 3 weeks, 95% protection was demonstrated at 6 weeks of age. The rHVT-AI vaccine demonstrated 95 and 100% protection at 3 and 6 weeks of age, respectively, of challenged broilers with reduced virus shedding compared to sham vaccinated birds. Finally, when the RP-H5 and rHVT vaccines were co-administered at one day of age, 95% protection was demonstrated with challenge at either 3 or 6 weeks age. In the second experiment, the highest protection (92%) was observed in the 108 RP-H5 vaccinated group. Significant reductions (p < 0.05) in virus shedding were observed in groups of vaccinated birds that were protected from challenge. The RG-H5 provided 62% protection from challenge. In all groups of surviving birds, antibody titers increased following challenge.

Conclusions
Overall, these results demonstrated several strategies that could be considered to protected broiler chickens during a H5 HPAI challenge.
Optimizing COVID-19 treatment in immunocompromised patients: early combination therapy with remdesivir, nirmatrelvir/ritonavir and sotrovimab
Authors: Gentile Ivan , Foggia Maria , Silvitelli Maria , Sardanelli Alessia , Cattaneo Letizia , Viceconte Giulio 
Published: December 2023

Abstract
Background
Morbidity and mortality are higher in immunocompromised patients affected by COVID-19 than in the general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection.

Methods
We conducted a retrospective cohort study to determine the efficacy and safety of the combination of two antivirals, with and without a monoclonal antibody (mAb), in both the early (within 10 days of symptoms) and in a later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our Facility.

Results
We treated 11 patients (seven in an early phase and four in a late phase of COVID-19) with 10 days of intravenous remdesivir plus five days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, all the “early” patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas the corresponding numbers in the “late” patients were 50% and 75%. Patients in the “late” group more frequently needed oxygen supplementation (p = 0.015) and steroid therapy (p = 0.045) during admission and reached higher COVID-19 severity (p = 0.017).

Discussion
The combination of antiviral and sotrovimab in the early phase of COVID-19 is well tolerated by immunocompromised patients and is associated with 100% of virological clearance. Patients treated later have lower response rates and higher disease severity, but whether therapy plays a causative role in such findings has yet to be determined.
Physical workload and cardiopulmonary parameters in relation to individual capacity of bulk waste workers – a cross-sectional field-study
Authors: Kraft Alexander Michael , Velasco Garrido Marcial , Herold Robert , Harth Volker , Preisser Alexandra Marita 
Published: December 2023

Abstract
Purpose
Waste collection is considered particularly heavy work, although no previous study has yet investigated the strain of bulk waste collection. The aim of this study is to determine the workload of bulk waste workers in practice.

Method
We conducted a cross-sectional field-study. Fourteen male volunteers from the bulk waste collection of the municipal sanitation department in Hamburg, Germany, were included. Performance was determined by cardiopulmonary exercise testing under laboratory conditions. During the shift, each worker was accompanied by a researcher, and heart rate (HR) was recorded under field conditions using an HR watch with a belt system. We examined mean HR, relative heart rate (RHR), relative aerobic strain (RAS), calculated oxygen uptake ($$\mathrm{\overset{.}{V}O}_2$$

V
.

O

2

) and individual ventilatory threshold 1 (VT1) as parameters of workload during their daily work.

Results
During the shift, HR was scaled: 102 bpm (SD 10.2), RHR: 36.9%, $$\mathrm{\overset{.}{V}O}_2$$

V
.

O

2

: 1267 ml/min (SD 161), RAS: 49.4% (SD 9.3), and $$\mathrm{\overset{.}{V}O}_2$$

V
.

O

2

in relation to VT1: 75% (SD 18.5). There was no significant difference between oxygen consumption during the main task of lifting and carrying bulky waste and the individual $$\mathrm{\overset{.}{V}O}_2$$

V
.

O

2

at VT1.

Conclusion
Although the burden of the main task of lifting and carrying bulky waste is very high (at VT1 for more than 3 h), interruptions from other tasks or formal breaks spread the burden over the entire shift. The total workload exceeded most recommendations in the literature across the different work periods. However, the total burden remains below VT1, the only parameter that takes individual endurance performance into account. We recommend again VT1 as an individual upper limit for prolonged occupational work.
The potential roles of gossypol as anticancer agent: advances and future directions
Authors: Paunovic Danijela , Rajkovic Jovana , Novakovic Radmila , Grujic-Milanovic Jelica , Mekky Reham Hassan , Popa Dragos , Calina Daniela , Sharifi-Rad Javad 
Published: December 2023

AbstractGossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations.The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol’s antineoplastic applications guided the search strategy.Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol’s promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects.Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.
Haematological reference intervals for pregnant Icelandic mares on pasture
Authors: Oddsdóttir Charlotta , Jónsdóttir Hanna Kristrún , Sturludóttir Erla 
Published: December 2023

Abstract
Background
Few studies have been conducted on haematological reference intervals (RIs) in Icelandic horses. Reference intervals have been published for Icelandic horses in Austria and a preliminary study in Iceland compared haematological values in riding horses to published RIs for other breeds as well as Icelandic horses abroad. Haematological parameters can vary greatly due to factors such as breed, gender, age, reproductive status, and training, as well as feeding, prior exercise and management method. Icelandic broodmares are kept on pasture under supervision throughout the year, with haylage provided during the winter, and it is therefore of interest to establish haematological reference intervals for pregnant broodmares in Iceland. The purpose of this study was to establish haematological RIs specific to Icelandic broodmares in the first months of pregnancy, kept on pasture. Blood samples from 183 mares, stabilised in EDTA were analysed using IDEXX ProCyte Dx and total protein was analysed in serum samples from 157 of the 183 mares, using IDEXX Catalyst One analyser. The RIs were established using the guidelines of the American Society for Veterinary Clinical Pathology.

Results
The RIs for red blood cell count, haematocrit and haemoglobin were higher in pasture-kept Icelandic mares in early pregnancy, most of which were lactating, than in pregnant mares of other breeds. This was also true for white blood cell count, as well as numbers of monocytes, eosinophils, and basophils, which in some instances might illustrate problems in the automated categorisation of some leukocytes.

Conclusions
As no RIs have been published for other pasture-kept Icelandic horses, future investigations should include other groups of pasture-kept Icelandic horses. Such an analysis might elucidate the effect of breed, management, and pregnancy on haematological values in pasture-kept Icelandic horses.
Pathophysiology of ion channels in amyotrophic lateral sclerosis
Authors: Stringer Robin N. , Weiss Norbert 
Published: December 2023

AbstractAmyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.
Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment
Authors: Loureiro Liliana R. , Hoffmann Lydia , Neuber Christin , Rupp Luise , Arndt Claudia , Kegler Alexandra , Kubeil Manja , Hagemeyer Christoph E. , Stephan Holger , Schmitz Marc , Feldmann Anja , Bachmann Michael 
Published: December 2023

Abstract
Background
Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression. Aiming to modulate the TME with increased clinical safety and effectiveness, we developed novel small and size-extended immunotheranostic UniCAR target modules (TMs) targeting FAP.

Methods
The specific binding and functionality of the αFAP-scFv TM and the size-extended αFAP-IgG4 TM were assessed using 2D and 3D in vitro models as well as in vivo. Their specific tumor accumulation and diagnostic potential were evaluated using PET studies after functionalization with a chelator and suitable radionuclide.

Results
The αFAP-scFv and -IgG4 TMs effectively and specifically redirected UniCAR T-cells using 2D, 3D, and in vivo models. Moreover, a remarkably high and specific accumulation of radiolabeled FAP-targeting TMs at the tumor site of xenograft mouse models was observed.

Conclusions
These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients.

Graphical Abstract
Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development
Authors: Jian Congcong , Wei Lingli , Wu Tong , Li Shilin , Wang Tingting , Chen Jianghua , Chang Shengjia , Zhang Jie , He Binhan , Wu Jianhong , Su Jiang , Zhu Jing , Wu Min , Zhang Yan , Zeng Fanxin 
Published: December 2023

Abstract
Objectives
Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis.

Methods
A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects.

Results
Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort.

Conclusions
These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
Neural EGFL-like 1, a craniosynostosis-related osteochondrogenic molecule, strikingly associates with neurodevelopmental pathologies
Authors: Li Chenshuang , Zheng Zhong , Ha Pin , Jiang Wenlu , Soo Chia , Ting Kang 
Published: December 2023

AbstractVarious craniofacial syndromes cause skeletal malformations and are accompanied by neurological abnormalities at different levels, leading to tremendous biomedical, financial, social, and psychological burdens. Accumulating evidence highlights the importance of identifying and characterizing the genetic basis that synchronously modulates musculoskeletal and neurobehavioral development and function. Particularly, previous studies from different groups have suggested that neural EGFL-like-1 (Nell-1), a well-established osteochondrogenic inducer whose biopotency was initially identified in the craniofacial tissues, may also play a vital role in the central nervous system, particularly regarding neurological disorder pathologies. To provide first-hand behavior evidence if Nell-1 also has a role in central nervous system abnormalities, we compared the Nell-1-haploinsufficient (Nell-1+/6R) mice with their wild-type counterparts regarding their repetitive, social communication, anxiety-related, locomotor, sensory processing-related, motor coordination, and Pavlovian learning and memory behaviors, as well as their hippocampus transcriptional profile. Interestingly, Nell-1+/6R mice demonstrated core autism spectrum disorder-like deficits, which could be corrected by Risperidone, an FDA-approved anti-autism, anti-bipolar medicine. Besides, transcriptomic analyses identified 269 differential expressed genes, as well as significantly shifted alternative splicing of ubiquitin B pseudogene Gm1821, in the Nell-1+/6R mouse hippocampus, which confirmed that Nell-1 plays a role in neurodevelopment. Therefore, the current study verifies that Nell-1 regulates neurological development and function for the first time. Moreover, this study opens new avenues for understanding and treating craniofacial patients suffering from skeletal deformities and behavior, memory, and cognition difficulties by uncovering a novel bone-brain-crosstalk network. Furthermore, the transcriptomic analysis provides the first insight into deciphering the mechanism of Nell-1 in neurodevelopment.
Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke
Authors: Liu Linquan , Cai Yahong , Deng Changqing 
Published: December 2023

Abstract
Background
Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS.

Methods
We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways.

Results
Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1β, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R.

Conclusion
This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis.
Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma
Authors: Ong Khaa Hoo , Lai Hong-Yue , Sun Ding-Ping , Chen Tzu-Ju , Huang Steven Kuan-Hua , Tian Yu-Feng , Chou Chia-Lin , Shiue Yow-Ling , Chan Ti-Chun , Li Chien-Feng , Kuo Yu-Hsuan 
Published: December 2023

AbstractCholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient’s prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.