bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herptile gut microbiomes: a natural system to study multi-kingdom interactions between filamentous fungi and bacteria
Authors: Vargas-Gastélum Lluvia , Romer Alexander S. , Ghotbi Marjan , Dallas Jason W. , Alexander N. Reed , Moe Kylie C. , McPhail Kerry L. , Neuhaus George F. , Shadmani Leila , Spatafora Joseph W. , Stajich Jason E. , Tabima Javier F. , Walker Donald M. 
Published: February 2024

ABSTRACT

Reptiles and amphibians (herptiles) are some of the most endangered and threatened species on the planet and numerous conservation strategies are being implemented with the goal of ensuring species recovery. Little is known, however, about the gut microbiome of wild herptiles and how it relates to the health of these populations. Here, we report results from the gut microbiome characterization of both a broad survey of herptiles, and the correlation between the fungus
Basidiobolus
, and the bacterial community supported by a deeper, more intensive sampling of
Plethodon glutinosus
, known as slimy salamanders. We demonstrate that bacterial communities sampled from frogs, lizards, and salamanders are structured by the host taxonomy and that
Basidiobolus
is a common and natural component of these wild gut microbiomes. Intensive sampling of multiple hosts across the ecoregions of Tennessee revealed that geography and host:geography interactions are strong predictors of distinct
Basidiobolus
operational taxonomic units present within a given host. Co-occurrence analyses of
Basidiobolus
and bacterial community diversity support a correlation and interaction between
Basidiobolus
and bacteria, suggesting that
Basidiobolus
may play a role in structuring the bacterial community. We further the hypothesis that this interaction is advanced by unique specialized metabolism originating from horizontal gene transfer from bacteria to
Basidiobolus
and demonstrate that
Basidiobolus
is capable of producing a diversity of specialized metabolites including small cyclic peptides.

IMPORTANCE
This work significantly advances our understanding of biodiversity and microbial interactions in herptile microbiomes, the role that fungi play as a structural and functional members of herptile gut microbiomes, and the chemical functions that structure microbiome phenotypes. We also provide an important observational system of how the gut microbiome represents a unique environment that selects for novel metabolic functions through horizontal gene transfer between fungi and bacteria. Such studies are needed to better understand the complexity of gut microbiomes in nature and will inform conservation strategies for threatened species of herpetofauna.
Impact of semen microbiota on the composition of seminal plasma
Authors: Baud D. , Zuber A. , Peric A. , Pluchino N. , Vulliemoz N. , Stojanov M. 
Published: February 2024

ABSTRACT

Several studies have found associations between specific bacterial genera and semen parameters. Bacteria are known to influence the composition of their niche and, consequently, could affect the composition of the seminal plasma. This study integrated microbiota profiling and metabolomics to explore the influence of seminal bacteria on semen metabolite composition in infertile couples, revealing associations between specific bacterial genera and metabolite profiles. Amino acids and acylcarnitines were the predominant metabolite groups identified in seminal plasma. Different microbiota profiles did not result in globally diverse metabolite compositions in seminal plasma. Nevertheless, levels of specific metabolites increased in the presence of a dysbiotic microbiota. Urocanate was significantly increased in abnormal semen samples (adjusted
P
-value < 0.001) and enriched in samples dominated by
Prevotella
spp. (
P
-value < 0.05), which was previously linked to a negative impact on semen. Therefore, varying microbiota profiles can influence the abundance of certain metabolites
,
potentially having an immunomodulatory effect, as seen with urocanate.

IMPORTANCE
Male infertility is often considered idiopathic since the specific cause of infertility often remains unidentified. Recently, variations in the seminal microbiota composition have been associated with normal and abnormal semen parameters and may, therefore, influence male infertility. Bacteria are known to alter the metabolite composition of their ecological niches, and thus, seminal bacteria might affect the composition of the seminal fluid, crucial in the fertilization process. Our research indicates that distinct seminal microbiota profiles are not associated with widespread changes in the metabolite composition of the seminal fluid. Instead, the presence of particular metabolites with immunomodulatory functions, such as urocanate, could shed light on the interplay between seminal microbiota and variations in semen parameters.
Two cases of linagliptin-associated bullous pemphigoid resulting in sepsis and endocarditis
Authors: Vanner Michael , Tanner Alexander , Chakera Ali 
Published: February 2024

We describe two patients, in their 70s, each presenting to the emergency department, with 6-week histories of progressively developing pruritic bullae. Both individuals had multiple comorbidities, including type 2 diabetes—for which they took linagliptin, chronic kidney disease, hypertension and prosthetic heart valves. Owing to systemic illness and endocarditis secondary to superadded bacterial infections, they both required intensive treatment and prolonged hospital admissions.Despite the beneficial effect of linagliptin on glycaemic control and its reported cardiovascular and renal safety profiles, we add our cases as evidence of the significant risk of developing bullous pemphigoid while taking this medication. Secondary infection of bullous pemphigoid increased the risk of developing endocarditis, particularly among individuals with a medical history of valve replacement surgery. Considering this, we advocate caution when prescribing this medication.
Clinicopathological characterisation ofMTAPalterations in gastrointestinal cancers
Authors: Mauri Gianluca , Patelli Giorgio , Roazzi Laura , Valtorta Emanuele , Amatu Alessio , Marrapese Giovanna , Bonazzina Erica , Tosi Federica , Bencardino Katia , Ciarlo Gabriele , Mariella Elisa , Marsoni Silvia , Bardelli Alberto , Bonoldi Emanuela , Sartore-Bianchi Andrea , Siena Salvatore 
Published: February 2024

BackgroundMethylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer,MTAPgene copy number loss (MTAPloss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact ofMTAPalterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable. Here, we aim to investigate the prevalence, clinicopathological features and prognosis ofMTAPloss GI cancers.MethodsCases withMTAPalterations were retrieved from The Cancer Genome Atlas (TCGA) and a real-world cohort of GI cancers profiled by next-generation sequencing. IfMTAPalterations other than loss were found, immunohistochemistry was performed. Finally, we set a case–control study to assessMTAPloss prognostic impact.ResultsFindings across the TCGA dataset (N=1363 patients) and our cohort (N=508) were consistent. Gene loss was the most commonMTAPalteration (9.4%), mostly co-occurring withCDKN2A/Bloss (97.7%). Biliopancreatic and gastro-oesophageal cancers had the highest prevalence ofMTAPloss (20.5% and 12.7%, respectively), being mostly microsatellite stable (99.2%). In colorectal cancer,MTAPloss was rare (1.1%), while mostMTAPalterations were mutations (5/7, 71.4%); among the latter, onlyMTAP-CDKN2Btruncation led to protein loss, thus potentially actionable.MTAPloss did not confer worse prognosis.ConclusionsMTAPalterations are found in 5%–10% of GI cancers, most frequently biliopancreatic and gastro-oesophageal.MTAPloss is the most common alteration, identified almost exclusively in MSS,CDKN2A/Bloss, upper-GI cancers. OtherMTAPalterations were found in colorectal cancer, but unlikely to cause protein loss and drug susceptibility.
Interferon Gamma Induces Higher Neutrophil Extracellular Traps Leading to Tumor-Killing Activity in Microsatellite Stable Colorectal Cancer
Authors: Teng Hao-Wei , Wang Tean-Ya , Lin Chun-Chi , Tong Zhen-Jie , Cheng Hsiao-Wei , Wang Hsiang-Tsui 
Published: February 2024

Abstract
Many patients with colorectal cancer do not respond to immune checkpoint blockade (ICB) therapy, highlighting the urgent need to understand tumor resistance mechanisms. Recently, the link between the IFNγ signaling pathway integrity and ICB resistance in the colorectal cancer tumor microenvironment has been revealed. The immunosuppressive microenvironment poses a significant challenge to antitumor immunity in colorectal cancer development. Tumor-associated neutrophils found in tumor tissues exhibit an immunosuppressive phenotype and are associated with colorectal cancer patient prognosis. Neutrophil extracellular traps (NET), DNA meshes containing cytotoxic enzymes released into the extracellular space, may be promising therapeutic targets in cancer. This study showed increased NETs in tumor tissues and peripheral neutrophils of high levels of microsatellite instability (MSI-H) patients with colorectal cancer compared with microsatellite stable (MSS) patients with colorectal cancer. IFNγ response genes were enriched in MSI-H patients with colorectal cancer compared with patients with MSS colorectal cancer. Co-culturing neutrophils with MSI-H colorectal cancer cell lines induced more NET formation and higher cellular apoptosis than MSS colorectal cancer cell lines. IFNγ treatment induced more NET formation and apoptosis in MSS colorectal cancer cell lines. Using subcutaneous or orthotopic CT-26 (MSS) tumor-bearing mice models, IFNγ reduced tumor size and enhanced PD-1 antibody-induced tumor-killing activity, accompanied by upregulated NETs and cellular apoptosis. These findings suggest that IFNγ could be a therapeutic strategy for MSS colorectal cancer.
SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter
Authors: Zhu Minhui , Ma Yi , Wang Wei , Li Meng , Chen Shicai , Liu Fei , Shi Xiaoqiong , Bi Hongsen , Zhang Chen , Nie Fangfei , Zheng Hongliang , Zhang Caiyun 
Published: February 2024

Abstract

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells.

Implications:
Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.
EFFICIENCY OF APPLICATION OF THE COMBINED HEPATOPROTECTOR IN COMPLEX TREATMENT OF CHRONIC PANCREATITIS WITH CONCOMITANT LIVER DAMAGE
Authors: Babinets L. S. , Kovalchuk K. M. 
Published: February 2024

SUMMARY. Comorbidity of chronic pancreatitis (CP) and chronic viral hepatitis C (CVHC) is quite common and problematic, even after etiotropic treatment of viral hepatitis C infection.
The aim – to investigate the state of the functional capacity of the pancreas and general clinical and selected biochemical parameters of patients with CP against the background of treated CVHC under the influence of the proposed complex treatment with the additional inclusion of the hepatotrophic drug heparizin (HZ).
Material and Methods. 45 patients with CP comorbid with CVHC were studied. All patients were examined according to generally accepted algorithms and received a generally accepted complex of treatment according to the protocol (GAT) for CP in accordance with the order of the Ministry of Health of Ukraine No. 638 dated 2014 and CVHC – according to the Clinical Guideline of the Ministry of Health of Ukraine, based on evidence "Viral Hepatitis C" dated 2020. All outpatient patients with a comorbid course of CP and CVHC were divided into 2 groups to study the effectiveness of the proposed correction programs: 1 group (20 patients) received a generally accepted complex of treatment according to the protocol (GAT) for three months, Group 2 (GAT+HZ) – 25 patients with CP and CVHC) – received GAT with the additional inclusion of the hepatotrophic agent Heparizin PLC, 1 capsule 3 times a day after meals for 3 months.
Results. A more significant level of effectiveness of the treatment complex with the additional inclusion of the hepatotrophic drug heparizin was established in relation to this protocol treatment for the restoration of the functional and structural state of the pancreas according to the studied parameters: the content of fecal α-elastase increased by 54.4 % vs. 39.9 %, respectively, and glucose content decreased – by 15.6 % vs. 10.0 %, the co-program score decreased – by 40.2 % vs. 25.1 %, the US score of the software structure decreased – by 74.4 % vs. 33.6 % (p <0.05).
Conclusions: The reliable positive effect of heparizin on the disturbed parameters of the functional state of the pancreas and liver in CP in combination with CVHC was proven and allowed to assert the anti-inflammatory activity of heparizin, optimizing its effect on protein metabolism and functions of the pancreas and liver. It is recommended to additionally include the hepatotrophic agent heparizin to the protocol complex therapy of patients with chronic pancreatitis against the background of treated etiologically CVHC at the stage of outpatient rehabilitative treatment.
ЗНАЧЕННЯ ПАРАМЕТРІВ ДОБОВОГО МОНІТОРУВАННЯ АРТЕРІАЛЬНОГО ТИСКУ В ПАЦІЄНТІВ ІЗ ЦУКРОВИМ ДІАБЕТОМ 2 ТИПУ Й АРТЕРІАЛЬНОЮ ГІПЕРТЕНЗІЄЮ
Authors: Батюх О. В. , Мазур Л. П. 
Published: February 2024

Важливим фактором ризику виникнення серцево-судинних захворювань вважають цукровий діабет 2 типу (ЦД 2 типу). Контроль артеріального тиску (АТ) і маси тіла є важливим елементом у системі заходів боротьби з розвитком можливих серцево-судинних ускладнень у пацієнтів із ЦД 2 типу.
Мета роботи – проаналізувати особливості добового індексу АТ, показники добового моніторування АТ у пацієнтів із ЦД 2 типу й артеріальною гіпертензією.
Основна частина. У дослідженні взяли участь 25 пацієнтів віком 39–74 роки. Обстежуваних поділили на дві групи. До 1-ї дослідної групи ввійшли 13 пацієнтів із ЦД 2 типу й артеріальною гіпертензією, з них 9 жінок віком 52–74 роки та 4 чоловіків віком 61–72 роки, до 2-ї – 12 хворих на ЦД 2 типу, з них 7 жінок віком 39–66 років і 5 чоловіків віком 41–64 роки. Для дослідження використовували монітор добового артеріального тиску «Heaco ABPM50». Інтервал вимірювання під час сну становив 60 хв, у період неспання – 30 хв. При визначенні добового індексу АТ профіль типу «дипер» виявлено в 4 обстежуваних 1-ї групи і 7 осіб 2-ї групи, профіль «нон дипер» – у 4 пацієнтів 1-ї групи та 5 хворих 2-ї групи, профілі «овер дипер» і «найт пікер» – лише у пацієнтів 1-ї групи (відповідно, 3 та 2 осіб). Середньодобові значення систолічного та діастолічного АТ у пацієнтів 1-ї групи достовірно перевищували показники хворих 2-ї групи. Середньодобовий пульс у пацієнтів 1-ї групи був дещо більший, але перебував у межах норми і становив 72,04 уд./хв, у хворих 2-ї групи – 70,44 уд./хв. Середньодобовий показник пульсового тиску в обстежуваних 1-ї групи становив 62,95 одиниці, що перевищувало допустимі межі, а в осіб 2-ї групи – 45,93 одиниці, що в межах допустимої норми.
Висновки. Аналіз показників холтерівського моніторування свідчить про значно вищі показники середньодобових значень артеріального тиску, пульсу, пульсового тиску в пацієнтів 1-ї групи (цукровий діабет 2 типу й артеріальна гіпертензія), що може бути пов’язано з рядом факторів ризику. Визначено, що моніторування параметрів артеріального тиску має прогностичне значення та дозволяє вчасно відкоригувати лікування пацієнтів з метою запобігання розвитку ускладнень.
ПОШИРЕНІСТЬ ЗАПАЛЬНИХ ЗАХВОРЮВАНЬ ОРГАНІВ МАЛОГО ТАЗА У ХВОРИХ НА ЦУКРОВИЙ ДІАБЕТ
Authors: Бадюк О. О. , Палапа В. В. , Оксюта В. М. , Габор Г. Г. 
Published: February 2024

Вступ. Як свідчать результати досліджень, жінки із запальними захворюваннями органів малого таза в анамнезі мали значно вищий ризик розвитку гіпертензії та цукрового діабету 2 типу. Соціальна значущість цієї групи патологій полягає у зниженні фертильності внаслідок виникнення серйозних ускладнень, що призводить до зниження якості життя пацієнток. У цьому дослідженні опрацьовано наукові публікації за останні роки, які доступні в мережі “Інтернет”, ключовими були слова “запальні захворювання органів малого таза”, “цукровий діабет”, “кардіометаболічні захворювання”, “ендометрит”, “параметрит”, “сальпінгіт”, “оофорит”. Незважаючи на порівняно меншу тривалість цукрового діабету 2 типу порівняно із цукровим діабетом 1 типу, ці пацієнтки однаково схильні до ризику розвитку репродуктивної дисфункції, що може бути пов’язано із супутнім ожирінням, синдромом полікістозних яєчників та ендо- або екзогенною гіперінсулінемією. Науково доведено, що, крім інфекцій статевих шляхів, такі захворювання, як ожиріння, порушення ліпідного метаболізму, й анамнез абортів також пов’язані з підвищеним ризиком безпліддя при запальних захворюваннях органів малого таза. Частота цукрового діабету також більша в жінок, які перенесли ці захворювання, тоді як у жінок із цукровим діабетом теж відзначають підвищений ризик їх розвитку. Встановлено помірні, значні статистичні зв’язки між інфекцією сечовивідних шляхів і запальними захворюваннями органів малого таза, інфекцією сечовивідних шляхів та цукровим діабетом. Інфекційні чинники запальних захворювань органів малого таза можуть сприяти розвитку кардіометаболічних розладів шляхом прямого впливу на судинну систему або непрямого системного впливу реакції на інфекцію. Мета дослідження – проаналізувати частоту розповсюдження та особливості перебігу запальних захворювань органів малого таза у хворих на цукровий діабет. Висновки. Аналіз наукової літератури свідчить про обмежені дані щодо епідеміології запальних захворювань органів малого таза та їх асоціацію із цукровим діабетом.
Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease
Authors: Marquis‐Gravel Guillaume , Stebbins Amanda , Wruck Lisa M. , Roe Matthew T. , Effron Mark B. , Hammill Bradley G. , Whittle Jeff , VanWormer Jeffrey J. , Robertson Holly R. , Alikhaani Jacqueline D. , Kripalani Sunil , Farrehi Peter M. , Girotra Saket , Benziger Catherine P. , Polonsky Tamar S. , Merritt J. Greg , Gupta Kamal , McCormick Thomas E. , Knowlton Kirk U. , Jain Sandeep K. , Kochar Ajar , Rothman Russell L. , Harrington Robert A. , Hernandez Adrian F. , Jones W. Schuyler 
Published: February 2024

Background
In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease.

Methods and Results

In the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow‐up: 26.2 months; interquartile range: 19.0–34.9 months). Median age was 67.6 years (interquartile range: 60.7–73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01–1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82–1.10]). The age–dose interaction was not significant (
P
=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (
P
>0.05 for all).

Conclusions
Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.
C1q/Tumor Necrosis Factor–Related Protein‐9 Is a Novel Vasculoprotective Cytokine That Restores High Glucose‐Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase
Authors: Hu Qingsong , Qu Wan , Zhang Tao , Feng Jianyi , Dong Xiaobian , Nie Ruqiong , Chen Junyu , Wang Xiaoqing , Peng Changnong , Ke Xiao 
Published: February 2024

Background
This study investigated whether gCTRP9 (globular C1q/tumor necrosis factor–related protein‐9) could restore high‐glucose (HG)‐suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS).

Methods and Results
EPCs were treated with HG (25 mmol/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed. Adiponectin receptor 1, adiponectin receptor 2, and N‐cadherin expression and AMP‐activated protein kinase, protein kinase B, and eNOS phosphorylation were measured by Western blotting. eNOS activity was determined using nitrite production measurement. In vivo reendothelialization and EPC homing assays were performed using Evans blue and immunofluorescence in mice. Treatment with gCTRP9 at physiological levels enhanced migration, adhesion, and tube formation of EPCs. gCTRP9 upregulated the phosphorylation of AMP‐activated protein kinase, protein kinase B, and eNOS and increased nitrite production in a concentration‐dependent manner. Exposure of EPCs to HG‐attenuated EPC functions induced cellular senescence and decreased eNOS activity and nitric oxide synthesis; the effects of HG were reversed by gCTRP9. Protein kinase B knockdown inhibited eNOS phosphorylation but did not affect gCTRP9‐induced AMP‐activated protein kinase phosphorylation. HG impaired N‐cadherin expression, but treatment with gCTRP9 restored N‐cadherin expression after HG stimulation. gCTRP9 restored HG‐impaired EPC functions through both adiponectin receptor 1 and N‐cadherin‐mediated AMP‐activated protein kinase /protein kinase B/eNOS signaling. Nude mice that received EPCs treated with gCTRP9 under HG medium showed a significant enhancement of the reendothelialization capacity compared with those with EPCs incubated under HG conditions.

Conclusions
CTRP9 promotes EPC migration, adhesion, and tube formation and restores these functions under HG conditions through eNOS‐mediated signaling mechanisms. Therefore, CTRP9 modulation could eventually be used for vascular healing after injury.