bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late‐Stage Diversification of Pyrazoles as Antileishmanial Agents
Authors: Winge Tobias , Perry Ben , Matheeussen An , Caljon Guy , Wünsch Bernhard 
Published: January 2024

AbstractN‐Pyrazolylcarboxamides and N‐pyrazolylureas represent promising lead compounds for the development of novel antileishmanial drugs. Herein, we report the late‐stage diversification of 3‐bromopyrazoles 10 A/B and 14 A by Pd‐catalyzed Sonogashira and Suzuki‐Miyaura cross coupling reactions. The electron‐withdrawing properties of the cyano moiety in 4‐position of the pyrazole ring limited the acylation of the primary amino moiety in 5‐position. A large set of pyrazoles bearing diverse aryl and alkynyl substituents in 3‐position was prepared and the antileishmanial and antitrypanosomal activity was recorded. The urea 38 lacking the electron withdrawing cyano moiety in 4‐position and containing the large 4‐benzylpiperidinoo moiety exhibited a modest antileishmanial (IC50=19 μM) and antitrypanosomal activity (IC50=7.9 μM)). However, its considerable toxicity against the PMM and MRC‐5 cells indicates low selectivity, i. e. a small gap between the desired antiparasitic activity and undesired cytotoxicity of <2‐ to 4‐fold.
Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti–PD‐L1, for BRCA wild‐type, platinum‐sensitive, recurrent ovarian cancer
Authors: Mutch David , Voulgari Athina , Chen Xian (Marissa) , Bradley William H. , Oaknin Ana , Perez Fidalgo José Alejandro , Montosa Fernando Galvez , Herraez Antonio Casado , Holloway Robert W. , Powell Matthew A. , Nowicka Malgorzata , Schaefer Gabriele , Merchant Mark , Yan Yibing 
Published: January 2024

AbstractBackgroundThis phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD‐L1 inhibition, for BRCA wild‐type, platinum‐sensitive, recurrent ovarian cancer (PSROC).MethodsPatients with PSROC who had received one or two prior treatment lines were treated with 28‐day cycles of cobimetinib 60 mg daily (days 1–21) plus niraparib 200 mg daily (days 1–28) with or without atezolizumab 840 mg (days 1 and 15). Stage 1 assessed safety before expansion to stage 2, which randomized patients who had BRCA wild‐type PSROC to receive either doublet or triplet therapy, stratified by genome‐wide loss of heterozygosity status (<16% vs. ≥16%; FoundationOne CDx assay) and platinum‐free interval (≥6 to <12 vs. ≥12 months). Coprimary end points were safety and the investigator‐determined objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Potential associations between genetic parameters and efficacy were explored, and biomarker profiles of super‐responders (complete response or those with progression‐free survival [PFS] >15 months) and progressors (disease progression as the best response) were characterized.ResultsThe ORR in patients who had BRCA wild‐type PSROC was 35% (95% confidence interval, 20%–53%) with the doublet regimen (n = 37) and 27% (95% confidence interval, 14%–44%) with the triplet regimen (n = 37), and the median PFS was 6.0 and 7.4 months, respectively. Post‐hoc analyses indicated more favorable ORR and PFS in the homologous recombination‐deficiency‐signature (HRDsig)‐positive subgroup than in the HRDsig‐negative subgroup. Tolerability was consistent with the known profiles of individual agents. NF1 and MKNK1 mutations were associated with sustained benefit from the doublet and triplet regimens, respectively.ConclusionsChemotherapy‐free doublet and triplet therapy demonstrated encouraging activity, including among patients who had BRCA wild‐type, HRDsig‐positive or HRDsig‐negative PSROC harboring NF1 or MKNK1 mutations.
MoNP‐doped Defective Carbon Fibers with Bark‐like Nanosurface as Effective Bifunctional Electrocatalysts for Zn‐air Batteries
Authors: Wang Jiangbo , Zhang Yanan , Liao Shiqin , Chen Dongsheng , Mensah Alfred , Wei Qufu 
Published: January 2024

AbstractThe flexible air electrode with high oxygen electrocatalytic performance and outstanding stability under various deformations plays a vital role in high‐performance flexible Zn‐air batteries (ZABs). Herein, a self‐supported Mo, N, and P co‐doped carbon cloth (CC) denoted as MoNP@CC with bark‐like surface structure is fabricated by a facile two‐step approach via a one‐pot method and pyrolysis. The surface of the electrode shows a nanoscale “rift valley” and uniformly distributed active sites. Taking advantage of the nano‐surface as well as transition metal and heteroatom doping, the self‐supported electrocatalysis air electrode exhibits considerable oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) performance in terms of low overpotential (388 mV at 10 mA cm−2) for OER and a much positive potential (0.74 V) at 1.0 mA cm−2 for ORR. Furthermore, MoNP@CC is further used for the flexible ZAB to demonstrate its practical application. The MoNP@CC‐based ZAB displays a good cycling performance for 2800 min and an open‐circuit voltage of 1.44 V. This work provides a new approach to the construction of a high‐performance, self‐supported electrocatalysis electrode used for a flexible energy storage device.
A sulfur‐modified pore‐blocking method to enhance the electrocatalytic stability of carbon‐supported platinum nanoparticles
Authors: Xie Yuhang , Wang Zhengluo , Xu Mingjie , Xiong Hongxi , Chen Yonglin , Wang Xiaohan , Yu Zelong , Zhou Weijiang , Tang Shuihua 
Published: January 2024

AbstractCurrently, the durability of electrode materials remains a big obstacle to the widespread adoption of proton exchange membrane fuel cells (PEMFCs). Herein thiourea and sodium dodecyl benzene sulfonate (SDS) were employed as sulfur source and carbon source to modify the pristine carbon black (Ketjen black EC300 J). A highly durable carbon supported Pt nanosized catalyst with higher platinum utilization for oxygen reduction reaction (ORR) in PEMFCs was produced by doping elemental sulfur into carbon supports and decreasing the carbon pore sizes and volume through a successive impregnation technique. The catalyst exhibits an initial activity of 0.167 A mgPt−1 at 0.90 V and demonstrates minimal activity loss after acceleration stress test (30,000 cycles of AST). The half‐wave potential loss for representative sample (Pt/S−C‐3) is only 14 mV with only 21.8 % ECSA decrease, 27.5 % MA loss and 5.9 % SA loss. A sintering test at various temperature shows a minor average size increase for sulfur‐doped carbon (S−C) supported one (from 2.09 to 2.52 nm). In single‐cell test, the MEA sample employing the platinum catalyst on modified carbon as cathode exhibited almost negligible performance loss after 30,000 cycles of AST.
γδ T cells mediate robust anti‐HIV functions during antiretroviral therapy regardless of immune checkpoint expression
Authors: Field Kirsty R , Wragg Kathleen M , Kent Stephen J , Lee Wen Shi , Juno Jennifer A 
Published: January 2024

AbstractObjectivesAlthough antiretroviral therapy (ART) efficiently suppresses HIV viral load, immune dysregulation and dysfunction persist in people living with HIV (PLWH). γδ T cells are functionally impaired during untreated HIV infection, but the extent to which they are reconstituted upon ART is currently unclear.MethodsUtilising a cohort of ART‐treated PLWH, we assessed the frequency and phenotype, characterised in vitro functional responses and defined the impact of immune checkpoint marker expression on effector functions of both Vδ1 and Vδ2 T cells. We additionally explore the in vitro expansion of Vδ2 T cells from PLWH on ART and the mechanisms by which such expanded cells may sense and kill HIV‐infected targets.ResultsA matured NK cell‐like phenotype was observed for Vδ1 T cells among 25 ART‐treated individuals (PLWH/ART) studied compared to 17 HIV‐uninfected controls, with heightened expression of 2B4, CD160, TIGIT and Tim‐3. Despite persistent phenotypic perturbations, Vδ1 T cells from PLWH/ART exhibited strong CD16‐mediated activation and degranulation, which were suppressed upon Tim‐3 and TIGIT crosslinking. Vδ2 T cell degranulation responses to the phosphoantigen (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate at concentrations up to 2 ng mL−1 were significantly impaired in an immune checkpoint‐independent manner among ART‐treated participants. Nonetheless, expanded Vδ2 T cells from PLWH/ART retained potent anti‐HIV effector functions, with the NKG2D receptor contributing substantially to the elimination of infected cells.ConclusionOur findings highlight that although significant perturbations remain within the γδ T cell compartment throughout ART‐treated HIV, both subsets retain the capacity for robust anti‐HIV effector functions.
Trichilemmal carcinoma metastatic to parotid gland: First report of fine needle aspiration cytology features
Authors: Jayakumar Priya , Kakkar Aanchal , Arava Sudheer , Mallick Supriya 
Published: January 2024

AbstractTrichilemmal carcinoma is a rare malignant cutaneous adnexal neoplasm arising from the outer root sheath of the hair follicle. Majority of cases occur on sun‐exposed sites such as the face, scalp and neck, making them easily amenable to being biopsied and subjected to histological examination for definitive diagnosis. Thus, cytological features of trichilemmal carcinoma have not been described till date. Trichilemmal carcinoma is a low‐grade malignancy, albeit with potential to metastasize to regional lymph nodes and distant sites. We report the case of trichilemmal carcinoma of scalp that metastasized to cervical lymph nodes and parotid gland and underwent fine‐needle aspiration cytology (FNAC) from the parotid lesion. The aspirate showed tightly cohesive cell clusters with sharp borders. Tumour cells ranged from basaloid with scant cytoplasm to those with abundant cytoplasm. Nuclei were vesicular, with inconspicuous to prominent nuclei. Intercellular bridges, masses of keratin, and fragments of desmoplastic stroma were present, closely recapitulating histological features of trichilemmal carcinoma, which enabled diagnosis as metastasis. Cell block showed similar tumour fragments with evidence of differentiation towards outer root sheath. FNAC is the first‐line investigation to obtain a tissue diagnosis of masses in the head and neck region. Although rarely encountered, the lack of knowledge of cytological features of trichilemmal carcinoma may hamper its FNAC diagnosis at metastatic sites. When intraparotid metastases occur, they may be mistaken as primary salivary gland carcinoma. Thus, awareness of the cytological features of this tumour must be raised among cytopathologists to enable accurate diagnosis and further management.
Diurnal temperature variation impacts energetics but not reproductive effort across seasons in a temperate dung beetle
Authors: Fleming J. Morgan , Marshall Katie E. , Coverley Alexander J. , Sheldon Kimberly S. 
Published: January 2024

AbstractTemperature varies on multiple timescales and ectotherms must adjust to these changes to survive. These adjustments may lead to energetic trade‐offs between self‐maintenance and reproductive investment. However, we know little about how diurnal and seasonal temperature changes impact energy allocation. Here we used a combination of empirical data and modeling of both thermoregulatory behaviors and body temperature to examine potential energetic trade‐offs in the dung beetle Onthophagus taurus. Beginning in March 2020, universities and laboratories were officially closed due to the COVID‐19 pandemic. We thus performed experiments at a private residence near Knoxville, Tennessee, USA, leveraging the heating, ventilation and air conditioning of the home to manipulate temperature and compare beetle responses to stable indoor temperatures versus variable outdoor temperatures. We collected O. taurus beetles in the early‐, mid‐, and late‐breeding seasons to examine energetics and reproductive output in relation to diurnal and seasonal temperature fluctuations. We recorded the mass of field fresh beetles before and after a 24‐h fast and used the resulting change in mass as a proxy for energetic costs of self‐maintenance across seasons. To understand the impacts of diurnal fluctuations on energy allocation, we held beetles either indoors or outdoors for 14‐day acclimation trials, fed them cow dung, and recorded mass change and reproductive output. Utilizing biophysical models, we integrated individual‐level biophysical characteristics, microhabitat‐specific performance, respirometry data, and thermoregulatory behaviors to predict temperature‐induced changes to the allocation of energy toward survival and reproduction. During 24 h of outdoor fasting, we found that beetles experiencing reduced temperature variation lost more mass than those experiencing greater temperature variation, and this was not affected by season. By contrast, during the 14‐day acclimation trials, we found that beetles experiencing reduced temperature variation (i.e., indoors) gained more mass than those experiencing greater temperature variation (i.e., outdoors). This effect may have been driven by shifts in the metabolism of the beetles during acclimation to increased temperature variation. Despite the negative relationship between temperature variation and energetic reserves, the only significant predictor of reproductive output was mean temperature. Taken together, we find that diurnal temperature fluctuations are important for driving energetics, but not reproductive output.
Taking a walk on the heart failure side: comparison of metabolic variables during walking and maximal exertion
Authors: Mapelli Massimo , Salvioni Elisabetta , Bonomi Alice , Paneroni Mara , Raimondo Rosa , Gugliandolo Paola , Mattavelli Irene , Bidoglio Jacopo , Mirza Kiran K. , La Rovere Maria Teresa , Gustafsson Finn , Agostoni Piergiuseppe 
Published: January 2024

AbstractAimsAlthough cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e., 6‐min walk test, 6MWT) are also commonly used. The aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicentre, heterogeneous population.MethodsWe included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement.ResultsWe enrolled 186 subjects (16 athletes, 40 healthy, 115 non‐LVAD HF patients, and 15 LVAD carriers). CPET‐peakV̇O2 was 41.0 [35.0–45.8], 26.2 [23.1–31.0], 12.8 [11.1–15.3], and 15.2 [13.6–15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (P < 0.001). During 6MWT they used 63.5 [56.3–76.8], 72.0 [57.8–81.0], 95.5 [80.3–109], and 95.0 [92.0–99.0] % of their peakV̇O2, respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT‐V̇O2 higher than their CPET‐peakV̇O2. Both 6MWT‐V̇O2 and walked distance were significantly associated with CPET‐peakV̇O2 in the whole population (R2 = 0.637 and R2 = 0.533, P ≤ 0.001) but not in the sub‐groups. This was confirmed after adjustment for groups.ConclusionsThe 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine.
The impact of different warm‐up strategies on acceleration and deceleration demands in highly trained soccer players
Authors: Silva Hugo , Nakamura Fábio Yuzo , Bajanca Catarina , Pinho Gonçalo , Loturco Irineu , Marcelino Rui 
Published: January 2024

AbstractThis study compared the differences in acceleration and deceleration demands between three different warm‐up (WU) strategies (Reaction speed [exercises with reaction to a stimulus], Run [self‐paced running], and Speed [exercises such as shuttle running or circuits]) applied to highly trained soccer players. Nineteen players were monitored for 4 weeks using a 10 Hz Global Positioning System. Accelerations and decelerations magnitudes were classified as low (25%–50%), moderate (50%–75%), and high (>75%) intensities. Additionally, efforts were analyzed according to their respective starting speeds (<5, 5–10, 10–15, 15–20, 20–25, and >25 km h−1). Differences between WU strategies were estimated via paired mean differences along with effect sizes. The three WU strategies led to few efforts starting >15 km h−1 and high‐intensity efforts (<1 effort per minute). Players performed more high‐intensity accelerations during Speed than Reaction Speed (ES: 0.74 [90% CI: 0.21, 1.33]); more moderate‐intensity accelerations during Reaction Speed than Run (ES: 1.29 [90% CI: 0.72, 2.00]); more moderate‐intensity decelerations during Reaction Speed than Run (ES: 0.64 [90% CI: 0.04, 1.32]) and Speed (ES: 0.89 [90% CI: 0.37, 1.50]); more decelerations started at 20–25 km h−1 during Speed than Reaction Speed (ES: 0.81 [90% CI: 0.20, 1.49]) and Run (ES: 0.76 [90% CI: 0.42, 1.18]); and more decelerations started at >25 km h−1 during Speed than Reaction Speed (ES: 3.57 [90% CI: 2.88, 4.58]). In conclusion, Speed elicited higher acceleration and deceleration demands than the Reaction Speed and Run WU strategies, and this should be considered when designing training sessions.
Enhancement of yogurt functionality by adding Mentha piprita phenolic extract and evaluation of its quality during cold storage
Authors: Guemidi Chafika , Ait Saada Djamal , Ait Chabane Ouiza , Elmastas Mahfuz , Erenler Ramazan , Yilmaz Mustafa Abdullah , Tarhan Abbas , Akkal Salah , Khelifi Haroune 
Published: January 2024

AbstractNew functional food products with health benefits are currently in high demand among health‐conscious consumers. The present research aims to improve the functional properties of yogurt by adding peppermint hydroethanolic extract (PHE) at different doses. The impact of PHE (0%, 2%, 4%, and 6%) on yogurt was studied for acidity, pH, organoleptic quality, antioxidant activity, lipid peroxidation, and fatty acid profile. The results revealed that PHE is rich in phenolic compounds, of which rosmarinic acid was the main one (339.88 mg/g lyophilized extract) and has considerable antioxidant potential, which remarkably (p < .01) increased antioxidant capacity in yogurt by over 39.51%, even at a low dose of 2%, giving the product better protection against lipid peroxidation and preserving its physicochemical and sensory quality. At 4%, PHE increased significantly (p < .01) the content of omega‐3 fatty acids, notably alpha‐linolenic acid, in fortified yogurt compared with the control, and reduced (p < .01) the ratio of omega‐6/omega‐3, which dropped from 5.21 to 4.11. It looks feasible to prepare a yogurt with health‐giving properties by adding Mentha piperita hydroethanolic extract at a concentration of up to 4% as an alternative to synthetic antioxidants, which would also extend its shelf life.
Production of low‐protein cocoa powder with enzyme‐assisted hydrolysis
Authors: Cerit İnci , Mehdizade Könül , Avcı Ayşe , Demirkol Omca 
Published: January 2024

AbstractAmino acid‐related disorders are caused by a defect in the metabolic pathways of amino acid groups. These patients must follow a lifelong protein diet. The objective of this study was to produce a low‐protein cocoa powder (LPP) with enzymatic hydrolysis and precipitation method. First, the solubility of cocoa powder was increased by heat and enzyme treatments (Amylase, Viscozyme, and Alcalase). Then, the protein level was decreased by isoelectric precipitation. According to the obtained results, the solubility of cocoa powder rose from 28.61% to 50.69%. Protein content decreased by almost 40% and significant reductions in the amino acid profile were also provided; the highest ones were detected in methionine (100%), lysine (73.65%), leucine (53.64%), alanine (46.17%), and isoleucine (44.73%) levels. LPP had high phenolic content (25.10 mg/g GAE) and the changes in the antioxidant activities were not significant (p > .05). Moreover, chocolate production with LPP and control powder was also carried out under laboratory conditions. Hardness (1732.52 g), moisture content (0.60%), and water activity (0.37) of chocolate samples produced with low‐protein cocoa powder (LPC) were lower than those of the control sample. The Casson model well fitted to the rheological data (R2 > .990) and chocolate samples showed elastic behavior. The removal of proteins from the cocoa was verified with Fourier transform infrared spectroscopy analyses. The melting temperatures of chocolates (31.84 and 31.54°C for control and LPC samples, respectively) did not change with the applied process. As a conclusion, it was revealed that the production of low‐protein cocoa powder and chocolate is feasible for patients with amino acid disorders with this study.
The trend of mortality rates following hospitals downgrading and closures due to outbreak of COVID‐19 in Fars province: A comparative cohort study
Authors: Fallahi Mohammad Javad , Seifbehzad Sarvin , Fereidooni Mehran , Farrokhi Amirmohammad , Ranjbar Keivan , Shahriarirad Reza 
Published: January 2024

AbstractBackground and AimsHospitals are one of the most important healthcare centers for providing the patients with different medical needs. Several different factors might cause hospitals to downgrade their services or departments or close down overall. One of the most multifaceted reasons for hospital downgrading or closure is infectious disease outbreaks. In this regard, we aimed to evaluate the effects of hospital closure and downgrading due to the COVID‐19 pandemic on the mortality rate of the people residing in Fars province, Iran.MethodsWe gathered mortality information, including the cause of death, age, sex, place, and time of death of all deceased cases occurring during a period of 3 years, from February 20, 2018 to March 2021 from the forensic medicine and also the Department of Biostatistics in Shiraz University of Medical Sciences.ResultsA total of 71,331 deaths have been reported since 2018 through the first quarter of 2021, with 57.9% of total mortality cases attributed to male gender. The total mortality counts ranged from 4229 to 9809 deaths per quarter, from which the minimum rate was reported in the first quarter of 2018 and the maximum in the fourth quarter of 2020. Based on the causes of death, diseases of the circulatory system were shown to be the all‐time most frequent cause of death, accounting for a total of 42.8% of recorded deaths, followed by neoplasms (9.77%) and diseases of the respiratory system (9.45%).ConclusionAlthough the large number of deaths at the time of the pandemic are immediately due to COVID‐19 infection, deaths due to a notable number of other causes have had a significant increase which, along with the specific trend of place and causes of death, shows that the downgrading and closure of hospitals have had a significant impact on overall population mortality.