bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composition and functional profiles of gut microbiota reflect the treatment stage, severity, and etiology of acute pancreatitis
Authors: Wang Zhenjiang , Guo Mingyi , Li Jing , Jiang Chuangming , Yang Sen , Zheng Shizhuo , Li Mingzhe , Ai Xinbo , Xu Xiaohong , Zhang Wenbo , He Xingxiang , Wang Yinan , Chen Yuping 
Published: September 2023

ABSTRACT

Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host’s metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways’ changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e.,
Bacteroides xylanisolvens
,
Clostridium lavalense,
and
Roseburia inulinivorans
) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species’ relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e.,
Oscillibacter
sp
.
57_20
, Parabacteroides johnsonii, Bacteroides stercoris, Methanobrevibacter smithii, Ruminococcus lactaris, Coprococcus comes,
and
Dorea formicigenerans
, which have the potential to identify the SAP at an early stage.

Importance
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host’s metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
Escherichia coli
cells are primed for survival before lethal antibiotic stress
Authors: Hossain Tahmina , Singh Abhyudai , Butzin Nicholas C. 
Published: September 2023

ABSTRACT
Non-genetic factors can cause significant fluctuations in gene expression levels. Regardless of growing in a stable environment, this fluctuation leads to cell-to-cell variability in an isogenic population. This phenotypic heterogeneity allows a tiny subset of bacterial cells in a population called persister cells to tolerate long-term lethal antibiotic effects by entering into a non-dividing, metabolically repressed state. We occasionally noticed a high variation in persister levels, and to explore this, we tested clonal populations starting from a single cell using a modified Luria-Delbrück fluctuation test. Although we kept the conditions same, the diversity in persistence level among clones was relatively consistent: varying from ~60- to 100- and ~40- to 70-fold for ampicillin and apramycin, respectively. Then, we divided and diluted each clone to observe whether the same clone had comparable persister levels for more than one generation. Replicates had similar persister levels even when clones were divided, diluted by 1:20, and allowed to grow for approximately five generations. This result explicitly shows a cellular memory passed on for generations and eventually lost when cells are diluted to 1:100 and regrown (>seven generations). Our result demonstrates (1) the existence of a small population prepared for stress (“primed cells”) resulting in higher persister numbers; (2) the primed memory state is reproducible and transient, passed down for generations but eventually lost; and (3) a heterogeneous persister population is a result of a transiently primed reversible cell state and not due to a pre-existing genetic mutation.

IMPORTANCE
Antibiotics have been highly effective in treating lethal infectious diseases for almost a century. However, the increasing threat of antibiotic resistance is again causing these diseases to become life-threatening. The longer a bacteria can survive antibiotics, the more likely it is to develop resistance. Complicating matters is that non-genetic factors can allow bacterial cells with identical DNA to gain transient resistance (also known as persistence). Here, we show that a small fraction of the bacterial population called primed cells can pass down non-genetic information (“memory”) to their offspring, enabling them to survive lethal antibiotics for a long time. However, this memory is eventually lost. These results demonstrate how bacteria can leverage differences among genetically identical cells formed through non-genetic factors to form primed cells with a selective advantage to survive antibiotics.
Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis
Authors: Roilides Emmanuel , Bradley John S. , Lonchar Julia , Huntington Jennifer A. , Wickremasingha Prachi , Su Feng-Hsiu , Bruno Christopher J. , Johnson Matthew G. 
Published: September 2023

ABSTRACT

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis included only neonates and young infants < 3 mo of age. The microbiologic modified intent-to-treat population (mMITT) included 20 patients (ceftolozane/tazobactam,
n
= 14; meropenem,
n
= 6). All patients had pyelonephritis at baseline; two patients in each treatment group had bacteremia (overall 4/20, 20%).
Escherichia coli
was the most common baseline pathogen (overall 16/20, 80%). Safety and efficacy results were similar between treatment groups and consistent with the overall pediatric population. There were no serious drug-related adverse events (AEs), no discontinuations due to AEs, and no AEs leading to death in either treatment group. For the ceftolozane/tazobactam and meropenem treatment groups, clinical cure rates in the mMITT population were 92.9% and 100%, respectively. The population PK analysis of neonates and young infants demonstrated similar ceftolozane and tazobactam exposures to those of adults, achieving pharmacodynamic targets associated with clinical and microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and achieves high clinical cure and microbiologic eradication rates in neonates and young infants < 3 mo of age with cUTI and pyelonephritis.

Importance

Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and young infants may not be appropriate; similarly, the clinical manifestations of infectious diseases and outcomes following antibacterial treatment may not be similar. Ceftolozane/tazobactam is an antibacterial drug combination active against
Pseudomonas aeruginosa
and other multidrug-resistant gram-negative bacteria. A clinical study led to the approval for ceftolozane/tazobactam in patients from birth to 18 y of age who have complicated urinary tract infections, including those with serious kidney infections. Based on data collected during that clinical study, we compared newborns and young infants who were treated with ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 patients). We found that ceftolozane/tazobactam treatment of newborns and young infants up to 3 mo of age who have complicated urinary tract infections demonstrated a favorable safety profile and high clinical cure and microbiologic eradication rates, similar to meropenem.
A unique record of prokaryote cell pyritization
Authors: Barling Nathan , Saleh Farid , Ma Xiaoya 
Published: September 2023

Abstract
Prokaryotes, including bacteria, are a major component of both modern and ancient ecosystems. Although fossilized prokaryotes are commonly discovered in sedimentary rocks, it is rare to find them preserved in situ alongside macrofossils, particularly as pyritized cells in sites of exceptional fossil preservation. We examined prokaryotes preserved in the Lower Cretaceous Crato Formation of Brazil and demonstrate the widespread presence of spherical microorganisms preserved on the surface of Crato invertebrate fossils. These microorganisms were pyritized, covering decaying carcasses, 1.14 ± 0.01 μm in size, hollow with smooth surfaces, and can be found as aggregates resembling modern prokaryotes, particularly, coccoid bacterial colonies. It is likely that the observed microorganisms covered the carcasses before permissive conditions were established for pyritization, which must have been so rapid as to inhibit the autolysis of their delicate membranes. This is a new record of prokaryote fossils preserved in pyrite in association with macrofossils, which highlights the unique diagenetic and paleoenvironmental conditions of the Crato Formation that facilitated this mode of fossilization.
Mustela strandi (Mustelidae, Carnivora) from the Early Pleistocene of Crimea
Authors: Gimranov D. O. , Jiangzuo Q. , Lavrov A. V. , Lopatin A. V. 
Published: September 2023

AbstractThe dentary of Mustela strandi Kormos, 1934 is described from the Lower Pleistocene deposits (Late Villafranchian, 1.8–1.5 Ma) of the Taurida cave in Crimea. It is the first finding of M. strandi in Russia. This extinct mustelid species is rarely found in the Lower and Middle Pleistocene of Central Europe.
Tumour-infiltrating lymphocyte subsets and their individual prognostic impact in oral squamous cell carcinoma
Authors: Kakkar Aanchal , Thakur Rishikesh , Roy Diya , Sood Ridhi , Sharma Atul , Malhotra Rajeev Kumar , Thakar Alok 
Published: September 2023

AimsCurrent understanding of oral squamous cell carcinoma (OSCC) is incomplete with regard to prognostic factors that lead to the considerable heterogeneity in treatment response and patient outcomes. We aimed to evaluate the impact of individual tumour-infiltrating lymphocyte (TIL) subsets on prognosis as a possible rationale for this, in a retrospective observational study.MethodsImmunohistochemistry was performed to quantitatively assess cell densities of CD3+, CD20+, CD4+, CD8+ and FOXP3+TIL subsets in 50 surgically treated OSCC cases. Results were correlated with disease-free survival (DFS) and overall survival (OS). Receiver operating characteristic curve analysis and Youden index were applied to determine prognostically significant cut-off values.ResultsMean counts for CD3+, CD4+, CD8+, CD20+ and FOXP3+TILs were 243, 52, 132, 53 and 116 cells per high power field, respectively. High CD8+ and low FOXP3+TIL counts, and high ratio of CD8:FOXP3 were significantly associated with longer DFS and OS, as well as with improved tumour–host interface parameters.ConclusionsHost immune response and its interaction with cancer cells have a significant impact on OSCC outcomes, with some TIL subsets being more clinically relevant than others. High cytotoxic T-cell (CD8) and low Treg (FOXP3) counts, and high cytotoxic T-cell to Treg (CD8:FOXP3) ratio are significantly associated with favourable prognosis. These results may serve as a leading point in identifying novel therapeutic agents that can redesign the tumour immune microenvironment by reducing infiltrating FOXP3-lymphocytes, and modifying their signalling pathways.
Astrophysical and electromagnetic emissivity properties of black holes surrounded by a quintessence type exotic fluid in the scalar–vector–tensor modified gravity
Authors: Sheikhahmadi Haidar , Soroushfar Saheb , Sajadi S. N. , Harko Tiberiu 
Published: September 2023

AbstractThe astrophysical consequences of the presence of a quintessence scalar field on the evolution of the horizon and on the accretion disk surrounding a static black hole, in the scalar–vector–tensor version of modified gravity (MOG), are investigated. The positions of the stable circular orbits of the massive test particles, moving around the central object, are obtained from the extremum of the effective potential. Detailed calculations are also presented to investigate the light deflection, shadow and Shapiro effect for such a black hole. The electromagnetic properties of the accretion disks that form around such black holes are considered in detail. The energy flux and efficiency parameter are estimated analytically and numerically. A comparison with the disk properties in Schwarzschild geometry is also performed. The quantum properties of the black hole are also considered, and the Hawking temperature and the mass loss rate due to the Hawking radiation are considered. The obtained results may lead to the possibility of direct astrophysical tests of black hole type objects in modified gravity theories.
Shadow and deflection angle of asymptotic, magnetically-charged, non-singular black hole
Authors: Kumaran Yashmitha , Övgün Ali 
Published: September 2023

AbstractIn this paper, we investigate a solution for an asymptotic, magnetically-charged, non-singular (AMCNS) black hole. By utilizing the Gauss–Bonnet theorems, we aim to unravel the intricate astrophysics associated with this unique black hole. The study explored various aspects including the black hole’s gravitational field, intrinsic properties, light bending, the shadow and greybody bounding of the black hole. Through rigorous calculations and simulations, we derive the weak deflection angle of the optical metric of AMCNS black hole. Additionally, we investigate the impact of the dark matter medium on the deflection angle, examined the distinctive features of the black hole’s shadow, and bound its greybody factors. Our findings not only deepen our understanding of gravitational lensing but also pave the way for future improvements in black hole theories by minimizing restrictive assumptions and incorporating a more realistic representation of these cosmic phenomena.
Interleukin-6 Facilitates Acute Myeloid Leukemia Chemoresistance via Mitofusin 1–Mediated Mitochondrial Fusion
Authors: Hou Diyu , Zheng Xiaoming , Cai Danni , You Ruolan , Liu Jingru , Wang Xiaoting , Liao Xinai , Tan Maoqing , Lin Liyan , Wang Jin , Zhang Shuxia , Huang Huifang 
Published: September 2023

Abstract

Acute myeloid leukemia (AML), an aggressive hematopoietic malignancy, exhibits poor prognosis and a high recurrence rate largely because of primary and secondary drug resistance. Elevated serum IL6 levels have been observed in patients with AML and are associated with chemoresistance. Chemoresistant AML cells are highly dependent on oxidative phosphorylation (OXPHOS), and mitochondrial network remodeling is essential for mitochondrial function. However, IL6-mediated regulation of mitochondrial remodeling and its effectiveness as a therapeutic target remain unclear. We aimed to determine the mechanisms through which IL6 facilitates the development of chemoresistance in AML cells. IL6 upregulated mitofusin 1 (MFN1)-mediated mitochondrial fusion, promoted OXPHOS, and induced chemoresistance in AML cells. MFN1 knockdown impaired the effects of IL6 on mitochondrial function and chemoresistance in AML cells. In an MLL::AF9 fusion gene-induced AML mouse model, IL6 reduced chemosensitivity to cytarabine (Ara-C), a commonly used antileukemia drug, accompanied by increased MFN1 expression, mitochondrial fusion, and OXPHOS status. In contrast, anti-IL6 antibodies downregulated MFN1 expression, suppressed mitochondrial fusion and OXPHOS, enhanced the curative effects of Ara-C, and prolonged overall survival. In conclusion, IL6 upregulated MFN1-mediated mitochondrial fusion in AML, which facilitated mitochondrial respiration, in turn, inducing chemoresistance. Thus, targeting IL6 may have therapeutic implications in overcoming IL6-mediated chemoresistance in AML.

Implications:
IL6 treatment induces MFN1-mediated mitochondrial fusion, promotes OXPHOS, and confers chemoresistance in AML cells. Targeting IL6 regulation in mitochondria is a promising therapeutic strategy to enhance the chemosensitivity of AML.
Change in Neighborhood Socioeconomic Status and Adherence to the Cancer Prevention Lifestyle Guidelines in Hispanic/Latino Adults: Results from the HCHS/SOL Study
Authors: Pichardo Margaret S. , Pichardo Catherine M. , Talavera Gregory A. , Gallo Linda C. , Kuo Charlene C. , Castañeda Sheila F. , Chambers Earle C. , Daviglus Martha L. , Pirzada Amber , Perreira Krista M. , Sotres-Alvarez Daniela , Peña Ortiz Tania Yadhira , Plascak Jesse J. 
Published: September 2023

Neighborhood conditions are dynamic; the association of changing neighborhood socioeconomic factors with cancer preventive behaviors remains unclear. We examined associations of neighborhood socioeconomic deprivation, gentrification, and change in income inequality with adherence to the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention in The Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The HCHS/SOL enrolled 16,415 adults, ages 18–74 years, at baseline (2008–2011), from communities in the Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA. Geocoded baseline addresses were linked to the 2000 decennial Census and 5-year American Community Survey (2005–2009 and 2012–2016) tracts to operationalize neighborhood deprivation index (NDI), gentrification, and income inequality. Complex survey multinominal logistic regression models estimated the relative risk ratio (RRR) with overall guideline adherence level (low, moderate, high) and by components—diet, physical activity, body mass index (BMI), and alcohol intake. Overall, 14%, 60%, and 26% of the population had low, moderate, and high ACS guideline adherence, respectively. NDI was negatively associated with risk of high (vs. low) guideline adherence [RRR = 0.87, 95% confidence interval (CI) = 0.78–0.98], although attenuated after controlling for individual socioeconomic status (SES; RRR = 0.89, 95% CI = 0.80–1.00), and associated with lower adherence to BMI recommendations (low vs. moderate RRR = 0.90, 95% CI = 0.84–0.97; high RRR = 0.86, 95% CI = 0.77–0.97). Gentrification was associated with higher likelihood of meeting the dietary recommendations (low vs. moderate RRR = 1.04, 95% CI = 1.01–1.07), but not with overall adherence or individual components. Change in income inequality was not associated with outcomes. Neighborhood deprivation may be negatively associated with ACS guideline adherence among Hispanic/Latino adults.

Significance:
This study provides new evidence on the link between neighborhood gentrification, changing income inequality and adoption and maintenance of cancer preventive behaviors in an understudied population in cancer research. We observed that while neighborhood deprivation may deter from healthy lifestyle behaviors, positive changes in neighborhood SES via the process of gentrification, may not influence lifestyle guideline adherence among Hispanic/Latino adults.
ВПРОВАДЖЕННЯ ЗАКОНУ УКРАЇНИ «ПРО ЛІКАРСЬКІ ЗАСОБИ» ЯК ФАКТОР РОЗВИТКУ ФАРМАЦЕВТИЧНОЇ ІНФОРМАТИКИ В НАЦІОНАЛЬНІЙ СИСТЕМІ ОХОРОНИ ЗДОРОВ’Я
Authors: Boiko A. I. 
Published: September 2023

Мета роботи. Провести аналіз ефективності та перспектив використання фундаментальних теоретичних досліджень з наукової дисципліни «Фармацевтична інформатика» (ФІ) при імплементації положень та реалізації вимог нового Закону України «Про лікарські засоби» (далі – Закон) (на моделі функціонування Львівської наукової школи з фармацевтичної інформатики (ЛНШФІ)) та інших вищих закладів освіти України.
Матеріали і методи. На основі системного підходу, використовуючи бібліосемантичний та структурно-логічний аналіз, виконано дослідження в якому використано результати теоретичних та експериментальних досліджень з ФІ впродовж 1978–2022 рр., законодавчі та нормативні акти в частинах, що регулюють систему фармацевтичної інформації.
Результати й обговорення. У статті проведено аналіз Закону щодо впровадження в ОЗ інтегрального комплексу фармацевтичної та медичної допомоги на основі методології ФІ. Системно розглянуті основні етапи та напрями комплексного функціонування фармацевтичних знань. Детально проаналізовано принципові, з позиції впровадження Закону, результати наукових досліджень з ФІ за встановленими автором напрямами. Обґрунтовано необхідність, відповідно до розглянутих регламентованих Законом проблемних питань розвитку фармацевтичної інформаційної складової в охороні здоров’я, системного вивчення інтеграції медичної та фармацевтичної допомоги хворим на цукровий діабет у вищій фармацевтичній школі України.
Висновки. Впроваджена в закладах вищої освіти України нова багатоаспектна наукова дисципліна ФІ інтегрує актуальні питання медичної та фармацевтичної теорії і практики в системі ОЗ. Відповідно, новий Закон акцентує необхідність активізації процесів інтеграції медичної та фармацевтичної допомоги. Систему теоретичних досліджень із ФІ реалізовано у комплексі дисертаційних досліджень, 6-ти монографіях та політематичних монографіях із профільними розділами; тезах доповідей у матеріалах з’їздів фармацевтів України; українському довідковому виданні «Фармацевтична енциклопедія»; актуальних ідеологічно інноваційних, оглядових та проблемних публікаціях у провідних медичних та фармацевтичних виданнях. Актуальними напрямами процесів інтеграції медичної та фармацевтичної допомоги є створення та використання в системі охорони здоров’я комп’ютерних фармацевтичних баз знань. Обґрунтовано актуальність використання комп’ютеризації рецептурного обігу для вивчення доцільності впровадження в Україні позитивно апробованого на міжнародному рівні досвіду індивідуалізації (персоніфікації) лікування пацієнтів.