bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caffeine, but Not Creatine, Improves Anaerobic Power Without Altering Anaerobic Capacity in Healthy Men During a Wingate Anaerobic Test
Authors: Marinho Alisson Henrique , Silva-Cavalcante Marcos David , Cristina-Souza Gislaine , Sousa Filipe Antonio de Barros , Ataide-Silva Thays , Bertuzzi Romulo , de Araujo Gustavo Gomes , Lima-Silva Adriano Eduardo 
Published: March 2024

There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p < .05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p = .01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p > .05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity.
Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Authors: Jogiraju Vamshi , Weber Elijah , Hindman Jason , West Steve , Ling John , Rhee Martin , Girish Sandhya , Palaparthy Ramesh , Singh Renu 
Published: March 2024

ABSTRACT

Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child–Pugh–Turcotte (CPT) Class B: score 7–9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal (
n
= 10) or impaired (
n
= 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration–time curve from time 0 to infinity (AUC
inf
) and maximum concentration (C
max
)] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUC
inf
and C
max
were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe and well tolerated in both studies. These results support the use of approved lenacapavir dosing regimen in patients with mild (CPT Class A: score 5–6) or moderate hepatic impairment as well as in patients with mild (60 ≤ CLcr ≤ 89 mL/min), moderate (30 ≤ CLcr ≤ 59 mL/min), and severe renal impairment.
Exploring the prokaryote-eukaryote interplay in microbial mats from an Andean athalassohaline wetland
Authors: Cubillos Carolina F. , Aguilar Pablo , Moreira David , Bertolino Paola , Iniesto Miguel , Dorador Cristina , López-García Purificación 
Published: March 2024

ABSTRACT

Microbial community assembly results from the interaction between biotic and abiotic factors. However, environmental selection is thought to predominantly shape communities in extreme ecosystems. Salar de Huasco, situated in the high-altitude Andean Altiplano, represents a poly-extreme ecosystem displaying spatial gradients of physicochemical conditions. To disentangle the influence of abiotic and biotic factors, we studied prokaryotic and eukaryotic communities from microbial mats and underlying sediments across contrasting areas of this athalassohaline ecosystem. The prokaryotic communities were primarily composed of bacteria, notably including a significant proportion of photosynthetic organisms like Cyanobacteria and anoxygenic photosynthetic members of Alpha- and Gammaproteobacteria and Chloroflexi. Additionally, Bacteroidetes, Verrucomicrobia, and Deltaproteobacteria were abundantly represented. Among eukaryotes, photosynthetic organisms (Ochrophyta and Archaeplastida) were predominant, alongside relatively abundant ciliates, cercozoans, and flagellated fungi. Salinity emerged as a key driver for the assembly of prokaryotic communities. Collectively, abiotic factors influenced both prokaryotic and eukaryotic communities, particularly those of algae. However, prokaryotic communities strongly correlated with photosynthetic eukaryotes, suggesting a pivotal role of biotic interactions in shaping these communities. Co-occurrence networks suggested potential interactions between different organisms, such as diatoms with specific photosynthetic and heterotrophic bacteria or with protist predators, indicating influences beyond environmental selection. While some associations may be explained by environmental preferences, the robust biotic correlations, alongside insights from other ecosystems and experimental studies, suggest that symbiotic and trophic interactions significantly shape microbial mat and sediment microbial communities in this athalassohaline ecosystem.

IMPORTANCE
How biotic and abiotic factors influence microbial community assembly is still poorly defined. Here, we explore their influence on prokaryotic and eukaryotic community assembly within microbial mats and sediments of an Andean high-altitude polyextreme wetland system. We show that, in addition to abiotic elements, mutual interactions exist between prokaryotic and eukaryotic communities. Notably, photosynthetic eukaryotes exhibit a strong correlation with prokaryotic communities, specifically diatoms with certain bacteria and other protists. Our findings underscore the significance of biotic interactions in community assembly and emphasize the necessity of considering the complete microbial community.
Improving medical record completeness at Wallaga University Referral Hospital: a multidimensional quality improvement project
Authors: Bayisa Gedefa , Gonfaa Lammii , Badasa Ketema , Dugasa Nemomsa , Abebe Mulugeta , Deressa Habtamu , Teshoma Regassa Misganu , Takele Amsalu , Tilahun Temesgen 
Published: March 2024

BackgroundAppropriately documented medical records enhance coordination, patient outcomes and clinical research.ObjectiveThe aim of this project was to improve Wallaga University Referral Hospital’s (WURH) medical record completeness rate from 53% to 80% from 1 January 2023 to 31 August 2023.MethodsA hospital-based interventional study was conducted at WURH. The Plan-Do-Study-Act cycle was used to test change ideas. A fishbone diagram and a driver diagram were used to identify root causes and address them. Key interventions consisted of supportive supervision, developing and distributing standardised formats, orientation for staff, establishing a chart audit team and assigning data owners.ResultOn the completion of the project, the overall implementation of inpatient medical record completeness increased from 53% to 82%. This improvement varies from department-to-department. It increased from 51% to 79%, 53% to 79%, 46% to 81% and 64% to 91% in the departments of internal medicine, paediatrics, obstetrics and gynaecology and surgery, respectively. The project brought improvements in the completeness of physician notes (84% to 100%), physician order sheet (54% to 84%), nursing care plan (26% to 69%), admission sheet (76% to 98%), discharge summary (94% to 98%), progress note (38% to 91%), medication administration (80% to 100%), appropriate attachment of documents (78% to 93%) and documentation of vital signs (50% to 100%).Conclusion and recommendationThe rate of medical record completeness was significantly improved in the study area. This was achieved through the application of multidimensional change ideas related to health professionals, supplies, health management information systems and leadership. However, in some of the parameters, the national targets were not met. Therefore, we recommend providing regular technical updates, conducting frequent chart audits and providing supportive supervision for the enhancement of medical record completeness. It is also advisable for the hospital management to work on its sustainability.
Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases
Authors: Oltmanns Friederike , Vieira Antão Ana , Irrgang Pascal , Viherlehto Vera , Jörg Leticia , Schmidt Anna , Wagner Jannik T , Rückert Michael , Flohr Ann-Sophie , Geppert Carol Imanuel , Frey Benjamin , Bayer Wibke , Gravekamp Claudia , Tenbusch Matthias , Gaipl Udo , Lapuente Dennis 
Published: March 2024

BackgroundGenerally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome.MethodsHere, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1β to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model.ResultsThe mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice.ConclusionIn summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments.
“QGP Signatures” revisited
Authors: Harris John W. , Müller Berndt 
Published: March 2024

AbstractWe revisit the graphic table of QCD signatures in our 1996 Annual Reviews article “The Search for the Quark–Gluon Plasma” and assess the progress that has been made since its publication towards providing quantitative evidence for the formation of a quark–gluon plasma in relativistic heavy-ion collisions and its characteristic properties.
NLO electroweak corrections to doubly-polarized $$W^+W^-$$ production at the LHC
Authors: Dao Thi Nhung , Le Duc Ninh 
Published: March 2024

AbstractWe present new results of next-to-leading order (NLO) electroweak corrections to doubly-polarized cross sections of $$W^+W^-$$

W
+

W
-

production at the LHC. The calculation is performed for the leptonic final state of $$e^{+}\mu _{e} \mu ^{-} {\bar{\nu }}_{\mu }$$

e
+

μ
e

μ
-

ν

¯

μ

using the double-pole approximation in the diboson center-of-mass frame. NLO QCD corrections and subleading contributions from the gg, $$b{\bar{b}}$$

b

b

¯

, $$\gamma \gamma $$

γ
γ

induced processes are taken into account in the numerical results. We found that NLO EW corrections are small for angular distributions but can reach tens of percent for transverse momentum distributions at high energies, e.g. reaching $$-40\%$$

-
40
%

at $$p_{T,e}\approx 300$$

p

T
,
e

≈
300

GeV. In these high $$p_T$$

p
T

regions, EW corrections are largest for the doubly-transverse mode.
Sharp spectral gap estimates for higher-order operators on Cartan–Hadamard manifolds
Authors: Farkas Csaba , Kajántó Sándor , Kristály Alexandru 
Published: March 2024

The goal of this paper is to provide sharp spectral gap estimates for problems involving higher-order operators (including both the clamped and buckling plate problems) on Cartan–Hadamard manifolds. The proofs are symmetrization-free — thus no sharp isoperimetric inequality is needed — based on two general, yet elementary functional inequalities. The spectral gap estimate for clamped plates solves a sharp asymptotic problem from [Q.-M. Cheng and H. Yang, Universal inequalities for eigenvalues of a clamped plate problem on a hyperbolic space, Proc. Amer. Math. Soc. 139(2) (2011) 461–471] concerning the behavior of higher-order eigenvalues on hyperbolic spaces, and answers a question raised in [A. Kristály, Fundamental tones of clamped plates in nonpositively curved spaces, Adv. Math. 367(39) (2020) 107113] on the validity of such sharp estimates in high-dimensional Cartan–Hadamard manifolds. As a byproduct of the general functional inequalities, various Rellich inequalities are established in the same geometric setting.
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors
Authors: Corcoran Ryan B. , Do Khanh T. , Kim Jeong E. , Cleary James M. , Parikh Aparna R. , Yeku Oladapo O. , Xiong Niya , Weekes Colin D. , Veneris Jennifer , Ahronian Leanne G. , Mauri Gianluca , Tian Jun , Norden Bryanna L. , Michel Alexa G. , Van Seventer Emily E. , Siravegna Giulia , Camphausen Kyle , Chi Gary , Fetter Isobel J. , Brugge Joan S. , Chen Helen , Takebe Naoko , Penson Richard T. , Juric Dejan , Flaherty Keith T. , Sullivan Ryan J. , Clark Jeffrey W. , Heist Rebecca S. , Matulonis Ursula A. , Liu Joyce F. , Shapiro Geoffrey I. 
Published: March 2024

Abstract

Purpose:
MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi.

Patients and Methods:
We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non–small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed.

Results:
A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit.

Conclusions:
Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.
Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry
Authors: Earle Nikki J. , Winbo Annika , Crawford Jackie , Wheeler Miriam , Stiles Rachael , Donoghue Tom , Stiles Martin K. , Hayes Ian , Marcondes Luciana , Martin Andrew , Skinner Jonathan R. 
Published: March 2024

BACKGROUND:
Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity.

METHODS:
Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed.

RESULTS:

Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Māori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the
MYBPC3
gene (60%) followed by the
MYH7
gene (24%). A P/LP variant was identified in 27% of Māori or Pacific probands versus 43% European or other ethnicity probands (
P
=0.022); 16% of Māori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (
P
=0.092). Women more often had a P/LP variant identified than men (48% versus 35%;
P
=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years;
P
<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (
P
=0.002).

CONCLUSIONS:
Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Māori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.
Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis
Authors: Manzo Onorina L. , Nour Jasmine , Sasset Linda , Marino Alice , Rubinelli Luisa , Palikhe Sailesh , Smimmo Martina , Hu Yang , Bucci Maria Rosaria , Borczuk Alain , Elemento Olivier , Freed Julie K. , Norata Giuseppe Danilo , Di Lorenzo Annarita 
Published: March 2024

BACKGROUND:
Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood.

METHODS:
We used an established model of coronary atherosclerosis in mice, combined with sphingolipidomics, RNA-sequencing, flow cytometry, and immunostaining to investigate the contribution of sphingolipid metabolism and signaling to endothelial cell (EC) activation and dysfunction.

RESULTS:

We demonstrated that hemodynamic stress induced an early metabolic rewiring towards endothelial sphingolipid de novo biosynthesis, favoring S1P signaling over ceramides as a protective response. This finding is a paradigm shift from the current belief that ceramide accrual contributes to endothelial dysfunction. The enzyme SPT (serine palmitoyltransferase) commences de novo biosynthesis of sphingolipids and is inhibited by NOGO-B (reticulon-4B), an ER membrane protein. Here, we showed that NOGO-B is upregulated by hemodynamic stress in myocardial EC of ApoE
−/−
mice and is expressed in the endothelium lining coronary lesions in mice and humans. We demonstrated that mice lacking NOGO-B specifically in EC (Nogo-A/B
ECKO
ApoE
−/−
) were resistant to coronary atherosclerosis development and progression, and mortality. Fibrous cap thickness was significantly increased in Nogo-A/B
ECKO
ApoE
−/−
mice and correlated with reduced necrotic core and macrophage infiltration. Mechanistically, the deletion of NOGO-B in EC sustained the rewiring of sphingolipid metabolism towards S1P, imparting an atheroprotective endothelial transcriptional signature.

CONCLUSIONS:
These data demonstrated that hemodynamic stress induced a protective rewiring of sphingolipid metabolism, favoring S1P over ceramide. NOGO-B deletion sustained the rewiring of sphingolipid metabolism toward S1P protecting EC from activation under hemodynamic stress and refraining coronary atherosclerosis. These findings also set forth the foundation for sphingolipid-based therapeutics to limit atheroprogression.
Epidermal Growth Factor‐Like Repeats and Discoidin I‐Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination
Authors: Zhao Mengmeng , Zheng Zihui , Peng Shanshan , Xu Yao , Zhang Jishou , Liu Jianfang , Pan Wei , Yin Zheng , Xu Shuwan , Wei Cheng , Wang Menglong , Wan Jun , Qin Juan‐Juan 
Published: March 2024

Background
Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor‐like repeats and discoidin I‐like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear.

Methods and Results
A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL‐1β (interleukin 1β) and TGF‐β (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin‐induced EndMT by promoting Smad4 deubiquitination in HUVECs.

Conclusions
Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.