bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of polyfunctional CD26highCD8+ T cells repertoire in chronic lymphocytic leukemia
Authors: Bozorgmehr Najmeh , Hnatiuk Mark , Peters Anthea C. , Elahi Shokrollah 
Published: January 2023

AbstractBackgroundCD8+ T cells play an essential role against tumors but the role of human CD8+CD26+ T cell subset against tumors, in particular, haematological cancers such as chronic lymphocytic leukemia (CLL) remains unknown. Although CD4+CD26highT cells are considered for adoptive cancer immunotherapy, the role of CD8+CD26+T cells is ill-defined. Therefore, further studies are required to better determine the role of CD8+CD26+T cells in solid tumors and haematological cancers.MethodsWe studied 55 CLL and 44 age-sex-matched healthy controls (HCs). The expression of CD26 on different T cell subsets (e.g. naïve, memory, effector, and etc.) was analyzed. Also, functional properties of CD8+CD26+and CD8+CD26−T cells were evaluated. Finally, the plasma cytokine/chemokine and Galectin-9 (Gal-9) levels were examined.ResultsCD26 expression identifies three CD8+T cell subsets with distinct immunological properties. While CD26negCD8+T cells are mainly transitional, effector memory and effectors, CD26lowCD8+T cells are mainly naïve, stem cell, and central memory but CD26high T cells are differentiated to transitional and effector memory. CD26+CD8+T cells are significantly reduced in CLL patients versus HCs. CD26high cells are enriched with Mucosal Associated Invariant T (MAIT) cells co-expressing CD161TVα7.2 and IL-18Rα. Also, CD26highcells have a rich chemokine receptor profile (e.g. CCR5 and CCR6), profound cytokine (TNF-α, IFN-γ, and IL-2), and cytolytic molecules (Granzyme B, K, and perforin) expression upon stimulation. CD26highand CD26lowT cells exhibit significantly lower frequencies of CD160, 2B4, TIGIT, ICOS, CD39, and PD-1 but higher levels of CD27, CD28, and CD73 versus CD26negcells. To understand the mechanism linked to CD26highdepletion, we found that malignant B cells by shedding Galectin-9 (Gal-9) contribute to the elevation of plasma Gal-9 in CLL patients. In turn, Gal-9 and the inflammatory milieu (IL-18, IL-12, and IL-15) in CLL patients contribute to increased apoptosis of CD26highT cells.ConclusionsOur results demonstrate that CD26+ T cells possess a natural polyfunctionality to traffic and exhibit effector functions and resist exhaustion. Therefore, they can be proposed for adoptive cancer immunotherapy. Finally, neutralizing and/or inhibiting Gal-9 may preserve CD26highCD8+T cells in CLL.
Lack of a protective effect of the Tmem106b “protective SNP” in the Grn knockout mouse model for frontotemporal lobar degeneration
Authors: Cabron Anne-Sophie , Borgmeyer Uwe , Richter Julia , Peisker Helga , Gutbrod Katharina , Dörmann Peter , Capell Anja , Damme Markus 
Published: January 2023

AbstractGenetic variants in TMEM106B are a common risk factor for frontotemporal lobar degeneration and the most important modifier of disease risk in patients with progranulin (GRN) mutations (FTLD-GRN). TMEM106B is encoding a lysosomal transmembrane protein of unknown molecular function. How it mediates its disease-modifying function remains enigmatic. Several TMEM106B single nucleotide polymorphisms (SNPs) are significantly associated with disease risk in FTLD-GRN carriers, of which all except one are within intronic sequences of TMEM106B. Of note, the non-coding SNPs are in high linkage disequilibrium with the coding SNP rs3173615 located in exon six of TMEM106B, resulting in a threonine to serine change at amino acid 185 in the minor allele, which is protective in FTLD-GRN carriers. To investigate the functional consequences of this variant in vivo, we generated and characterized a knockin mouse model harboring the Tmem106bT186S variant. We analyzed the effect of this protective variant on FTLD pathology by crossing Tmem106bT186S mice with Grn−/− knockout mice, a model for GRN-mediated FTLD. We did not observe the amelioration of any of the investigated Grn−/− knockout phenotypes, including transcriptomic changes, lipid alterations, or microgliosis in Tmem106bT186S/T186S × Grn−/− mice, indicating that the Tmem106bT186S variant is not protective in the Grn−/− knockout mouse model. These data suggest that effects of the associated SNPs not directly linked to the amino acid exchange in TMEM106B are critical for the modifying effect.
Comparison of the effect of Triticum Vulgare and Hyperici Oleum on healing in traumatic membrane perforation: an animal study
Authors: Bora Adem , Durmuş Kasım , İnan Zeynep D.Şahin , Demirkıran Berat Baturay , Altuntas Emine E. 
Published: January 2023

Abstract
Background
Traumatic tympanic membrane (TM) perforations usually heal spontaneously. The aim of this study was to investigate whether the topical application of Triticum Vulgare (TV) in experimentally induced traumatic TM perforations in the rats has a positive effect on wound healing process.

Methods
The rats were randomly assigned to four experimental groups. Drugs were introduced twice a day for 7 days. On the 7th day, specimens were sent for histological examination.

Results
Mean values found in group NC in terms of epithelial regeneration mean scores are as follows: fibroblast and collagen density, neovascularization, and density of inflammation cells were lower than all groups (p < 0.05).
It was found that reepithelization on the post-perforation 7th day was better in the HO group than the TV group. In terms of the subepithelial fibroblast cells, density of collagen fibers, formation of new veins, and inflammatory cell accumulation, it was observed that the group TV was better than the group HO.

Conclusion
This is the first study investigating the potential curative role of TV in an experimental rat model of tympanic membrane perforation. Considering these findings, it is concluded that TV can be more effective than HO on wound healing in TM perforation.
A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy
Authors: Liu Shuwei , Fu Haoyi , Ray Mitali , Heinsberg Lacey W. , Conley Yvette P. , Anderson Cindy M. , Hubel Carl A. , Roberts James M. , Jeyabalan Arun , Weeks Daniel E. , Schmella Mandy J. 
Published: January 2023

AbstractBackgroundWhile preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls).ResultsIn the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases,n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significancepvalue threshold of 9×10-8, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×10-5. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases,n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated withTRAF3IP2-AS1/TRAF3IP2genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample.ConclusionsThe discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase.
Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis
Authors: Cookson John , Pimm Jonathan , Reynolds Gavin 
Published: January 2023

SUMMARYPartial agonists of dopamine receptors are used in combination with full antagonists in treating psychosis, either to mitigate side-effects or in the hope of increasing effectiveness. We examine how combinations may affect the occupancy of D2/D3dopamine receptors and explore how these can explain the outcomes in the light of the dopamine hypothesis of psychosis. The combinations considered here are from published studies combining aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia and with olanzapine to mitigate weight gain. We discuss possible worsening of symptoms by the addition of a partial agonist or switching. We also examine the potentially adverse interaction with a full antagonist such as haloperidol given during a subsequent relapse to control severe agitation.
Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation
Authors: Patil Vijay Maruti , Noronha Vanita , Menon Nandini , Singh Ajay , Ghosh-Laskar Sarbani , Budrukkar Ashwini , Bhattacharjee Atanu , Swain Monali , Mathrudev Vijayalakshmi , Nawale Kavita , Balaji Arun , Peelay Zoya , Alone Mitali , Pathak Shruti , Mahajan Abhishek , Kumar Suman , Purandare Nilendu , Agarwal Archi , Puranik Ameya , Pendse Shantanu , Reddy Yallala Monica , Sahu Harsh , Kapu Venkatesh , Dey Sayak , Choudhary Jatin , Krishna Madala Ravi , Shetty Alok , Karuvandan Naveen , Ravind Rahul , Rai Rahul , Jobanputra Kunal , Chaturvedi Pankaj , Pai Prathamesh S. , Chaukar Devendra , Nair Sudhir , Thiagarajan Shivakumar , Prabhash Kumar 
Published: January 2023

PURPOSE There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC. [Media: see text]
Activation of PDGF Signaling in the Adult Muscle Stem Cell Niche in Patients With Type 2 Diabetes Mellitus
Authors: Fahrner Alexandra , Alchus Laiferová Nikoleta , Ukropcová Barbara , Ukropec Jozef , Krützfeldt Jan 
Published: January 2023

AbstractContextType 2 diabetes mellitus (T2D) negatively affects muscle mass and function throughout life. Whether adult muscle stem cells contribute to the decrease in muscle health is not clear and insights into the stem cell niche are difficult to obtain.ObjectiveTo establish the upstream signaling pathway of microRNA (miR)-501, a marker of activated myogenic progenitor cells, and interrogate this pathway in muscle biopsies from patients with T2D.MethodsAnalysis of primary muscle cell cultures from mice and 4 normoglycemic humans and muscle biopsies from 7 patients with T2D and 7 normoglycemic controls using gene expression, information on histone methylation, peptide screening, and promoter assays.ResultsmiR-501 shares the promoter of its host gene, isoform 2 of chloride voltage-gated channel 5 (CLCN5-2), and miR-501 expression increases during muscle cell differentiation. We identify platelet-derived growth factor (PDGF) as an upstream regulator of CLCN5-2 and miR-501 via Janus kinase/signal transducer and activator of transcription. Skeletal muscle biopsies from patients with T2D revealed upregulation of PDGF (1.62-fold, P = .002), CLCN5-2 (2.85-fold, P = .03), and miR-501 (1.73-fold, P = .02) compared with normoglycemic controls. In addition, we observed a positive correlation of PDGF and miR-501 in human skeletal muscle (r = 0.542, P = .045, n = 14).ConclusionsWe conclude that paracrine signaling in the adult muscle stem cells niche is activated in T2D. Expression analysis of the PDGF–miR-501 signaling pathway could represent a powerful tool to classify patients in clinical trials that aim to improve muscle health and glucose homeostasis in patients with diabetes.
Hematopoietic Stem Cells and Metabolic Deterioration in Alström Syndrome, a Rare Genetic Model of the Metabolic Syndrome
Authors: Dassie Francesca , Albiero Mattia , Bettini Silvia , Cappellari Roberta , Milan Gabriella , Ciciliot Stefano , Naggert Jurgen K , Avogaro Angelo , Vettor Roberto , Maffei Pietro , Fadini Gian Paolo 
Published: January 2023

Abstract
Alström syndrome (AS) is a rare genetic disease caused by ALMS1 mutations, characterized by short stature, and vision and hearing loss. Patients with AS develop the metabolic syndrome, long-term organ complications, and die prematurely. We explored the association between AS and a shortage of hematopoietic stem/progenitor cells (HSPCs), which is linked to metabolic diseases and predicts diabetic complications. We included patients with AS at a national referral center. We measured HSPCs with flow cytometry at baseline and follow-up. We followed patients up to January 2022 for metabolic worsening and end-organ damage. We evaluated HSPC levels and mobilization as well as bone marrow histology in a murine model of AS. In 23 patients with AS, we found significantly lower circulating HSPCs than in healthy blood donors (−40%; P = .002) and age/sex-matched patients (−25%; P = .022). Longitudinally, HSPCs significantly declined by a further 20% in patients with AS over a median of 36 months (interquartile range 30-44). Patients with AS who displayed metabolic deterioration over 5.3 years had lower levels of HSPCs, both at baseline and at last observation, than those who did not deteriorate. Alms1-mutated mice were obese and insulin resistant and displayed significantly reduced circulating HSPCs, despite no overt hematological abnormality. Contrary to what was observed in diabetic mice, HSPC mobilization and bone marrow structure were unaffected. We found depletion of HSPCs in patients with AS, which was recapitulated in Alms1-mutated mice. Larger and longer studies will be needed to establish HSPCs shortage as a driver of metabolic deterioration leading to end-organ damage in AS.
Investigation of some acute phase proteins, cytokines and hepcidin values in feline enteric corona virus antibodies and feline infectious peritonitis antigen positive cats
Authors: Şahinduran Ş , Albay MK , Karaca M , Karakurum MÇ , Kiyici R 
Published: January 2023

Feline Infectious Peritonitis (FIP) is a fatal disease caused by feline coronaviruses. The causative agent is Feline Infectious Peritonitis Virus, a mutation of Feline Enteric Coronavirus. Feline Corona Virus is very common in the cat population. In Feline Corona Virus infected cats, the development of FIP depends on the cat's immune response. FIP disease is more common in young and old cats because young and old animals have a weaker immune system. The acute phase response is a complex systemic reaction that occurs as a response to acute or chronic inflammatory processes such as infection, neoplasia or immunological disorders, tissue damage, trauma and surgery. The study material included 15 cat with presumptive FIP (study group) and 10 healthy cats (control group). Of the 15 cats, 9 (60%) showed dry and 6 (40%) effusive form. Serum amyloid A (SAA), haptoglobin (Hp), α1-acid glycoprotein (AGP), albumin, interleukin-6 (IL-6), hepcidin, alanine-amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen(BUN), and creatinine levels were measured in the serum collected from both groups. There were no difference between the wet and dry FIP in albumin values; haptoglobin, α1-acid glycoprotein, SAA and hepcidin values were significantly different between the two groups. IL-6, showed significant difference in both wet and dry FIP groups. It was also concluded that hepcidin may be used as a biomarker in Feline Infectious Peritonitis disease like other acute phase proteins.
Study on the frequency and chemical composition of urinary stones of Moghani sheep in Northwest of Iran
Authors: Nozohour Y , Najarnezhad V 
Published: January 2023

Nephrolithiasis is one of the most important urinary tract diseases of ruminants and a costly problem for many sheep and goat owners. Therefore, it is important to analyse the composition of renal stone to prevent the formation of these kind of stones. The aim of the present study was to determine the frequency and the chemical constituents of urinary stones of Moghani sheep in Northwest of Iran. The kidneys, ureters, and urinary bladders of 384 Moghani sheep were examined carefully. The prevalence of urinary stones was 3.7%. All the stones were in the pelvis of the kidney and no stones were found in the ureter or urinary bladder. Macroscopically, 85.7% of the urinary stones showed a rough (jagged) appearance and 12.3% of them a smooth appearance. The largest and smallest urinary stones were 7 mm and 2 mm in diameter and 0.600 g and 0.087 g in weight, respectively. The composition of calculi were pure or mixed and included calcium oxalate (44.44%), magnesium ammonium phosphate (33.33%) and calcium carbonate (22.22%). Calcium oxalate was the major constituent in the urinary stone, hence, grazing on the pasture plants containing oxalate should be limited. More detail studies should be designed to clarify the contribution of environmental and nutritional factors in development of urinary stones.
Effects of Beta Vinasse Supplementation on Performance, Meat Quality and Ilio- Caecal Microflora in Quail Rations
Authors: Yeşilbağ DY , Cetin I , Cengiz SS , Cetin E , Sarpasar M 
Published: January 2023

The aim of this study was to evaluate the effects of β-vinasse supplementation on the live weight (LW), live weight gain (LWG), feed intake (FI), feed conversion ratio (FCR), carcass yield, meat quality and ilio-caecal bacteriological flora of quails. A total of 240 5-d-old Japanese (Coturnix coturnix Japonica) quails, including both males and females, were divided into 3 groups 80 quails and treated as follow: a control group with 0 g β-vinasse/kg ration; (2) 15 g/kg β-vinasse and (3) 30 g/kg β-vinasse. The study lasted for 6 weeks. At the end of the experiment, suplementation with β-vinasse did not have significant effect on FI and FCR. Dietary supplementation with 30 g/kg β-vinasse significantly (P < 0.05) increased LW (21 d) and LWG (5 to 21 d). The dietary treatment of quails with different levels of β- vinasse did not effect on hot carcass weight, cold carcass weights, hot and cold carcass yields and breast and thigh pH. The lightness (L*) and yellowness (b*) of breast values were significantly (P<0.05) increased of 30 g/kg supplementation. Different levels of β-vinasse significantly increased Lactobacillus spp. in faeces. As a result, it was concluded that β-vinasse (by-product obtained from molasses) can be used in quail diets as an alternative feed source that will meet the nutritional needs of the animal and have positive effects on the digestive system, especially on the intestinal health ( an increase in Lactobacillus spp. counts).
Pre- and post -exercise variation of blood parameters on performance endurance horses: a first race study from Algeria
Authors: Chikhaoui M , Fadhéla S , Belalia CZA , Ayad N 
Published: January 2023

Abstract: This paper presents the first study conducted in Algeria to determine the pre and post-race hematological and biochemical parameters of horses of a 90 km endurance race for eliminated horses’ category and those who completed the races with good performance. This study was conducted on 15 endurance horses (10 Arabian Thoroughbred, 4 Arabian-Barb and 1 Barb). Nine (9) horses successfully completed the endurance race, whereas the other 6 were eliminated. Blood samples were collected from each animal before and after the end of the race. Whole blood samples were used for measuring the blood-biochemical parameters. Our results showed a significant increase in the hematological parameters (RBC, HB, Ht and MCV), the total leucocyte count, neutrophils and platelets for the group of horses who finished the race successfully. A significant decrease was noticed for the lymphocytes and eosinophils numbers while serum biochemical parameters showed a significant increase of Ca, TG, urea, U-A, AST and CK and a decrease of Mg, CHE, GLU and ƔGT. This study showed that, for the eliminated horses, there were significant changes in values of the total leucocytic count, lymphocytes, neutrophils, HB and Ht as compared to good performance horses. Serum biochemical parameters showed a significant increase of TG, U-A, AST and CK and a significant decrease of Ca, Mg, CHE and ƔGT. Most of the hemato-biochemical parameters of both the eliminated horses and those who completed the race successfully depicted significant differences. The results of this study suggested that biochemical findings could help identify horses with an increased risk of developing metabolic alterations before their elimination during competitive endurance races of different distances. Therefore, proper management protocols, standard feeding and watering with proper preparation of animals before the race could prevent electrolytes imbalance and pathological affections during racing.