bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Alterations in Pulmonary V˙O2 and Muscle Deoxygenation On-Kinetics During Heavy-Intensity Exercise in Competitive Youth Cyclists: A Cohort Study
Authors: Hovorka Matthias , Prinz Bernhard , Simon Dieter , Zöger Manfred , Rumpl Clemens , Nimmerichter Alfred 
Published: May 2024

Purpose: The aim of this investigation was to assess alterations of pulmonary oxygen uptake () and muscle deoxygenation on-kinetics during heavy-intensity cycling in youth cyclists over a period of 15 months. Methods: Eleven cyclists (initial age, 14.3 [1.6] y; peak , 62.2 [4.5] mL·min−1·kg−1) visited the laboratory twice on 3 occasions within 15 months. Participants performed an incremental ramp exercise test and a constant workrate test within the heavy-intensity domain during the first visit and second visit, respectively. Subsequently, parameter estimates of the and muscle deoxygenation on-kinetics were determined with mono-exponential models. Results: The phase II time constant decreased from occasion 1 (34 [4] s) to occasion 2 (30 [4] s, P = .005) and 3 (28 [4] s, P = .010). However, no significant alteration was observed between occasions 2 and 3 (P = .565). The slow component amplitude either expressed in absolute values (ie, L·min−1) or relative to end exercise (ie, %) showed no significant changes throughout the study (P = .972 and .996). Furthermore, the muscle deoxygenation on-kinetic mean response time showed no significant changes throughout the study (18 [8], 18 [3], and 16 [5] s for occasions 1, 2, and 3, respectively; P = .279). Conclusion: These results indicate proportional enhancements of local muscle oxygen distribution and utilization, which both contributed to the speeding of the on-kinetics herein.
The
Streptococcus pyogenes
stand-alone regulator RofA exhibits characteristics of a PRD-containing virulence regulator
Authors: Hart Meaghan T. , Rom Joseph S. , Le Breton Yoann , Hause Lara L. , Belew Ashton T. , El-Sayed Najib M. , McIver Kevin S. 
Published: May 2024

ABSTRACT

Streptococcus pyogenes
[group A streptococcus (GAS)] is a human pathogen capable of infecting diverse tissues. To successfully infect these sites, GAS must detect available nutrients and adapt accordingly. The phosphoenolpyruvate transferase system (PTS) mediates carbohydrate uptake and metabolic gene regulation to adapt to the nutritional environment. Regulation by the PTS can occur through phosphorylation of transcriptional regulators at conserved PTS-regulatory domains (PRDs). GAS has several PRD-containing stand-alone regulators with regulons encoding both metabolic genes and virulence factors [PRD-containing virulence regulators (PCVRs)]. One is RofA, which regulates the expression of virulence genes in multiple GAS serotypes. It was hypothesized that RofA is phosphorylated by the PTS in response to carbohydrate levels to coordinate virulence gene expression. In this study, the RofA regulon of M1T1 strain 5448 was determined using RNA sequencing. Two operons were consistently differentially expressed across growth in the absence of RofA; the pilus operon was downregulated, and the capsule operon was upregulated. This correlated with increased capsule production and decreased adherence to keratinocytes. Purified RofA-His was phosphorylated
in vitro
by PTS proteins EI and HPr, and phosphorylated RofA-FLAG was detected
in vivo
when GAS was grown in low-glucose C medium. Phosphorylated RofA was not observed when C medium was supplemented 10-fold with glucose. Mutations of select histidine residues within the putative PRDs contributed to the
in vivo
phosphorylation of RofA, although phosphorylation of RofA was still observed, suggesting other phosphorylation sites exist in the protein. Together, these findings support the hypothesis that RofA is a PCVR that may couple sugar metabolism with virulence regulation.
Comparison of BD Phoenix and disk diffusion to broth microdilution for determining cefepime susceptibility among carbapenem-resistant Enterobacterales
Authors: Fouad Aliaa , Simner Patricia J. , Nicolau David P. , Asempa Tomefa E. 
Published: May 2024

ABSTRACT

There are increasing reports of carbapenem-resistant Enterobacterales (CRE) that test as cefepime-susceptible (S) or susceptible-dose dependent (SDD). However, there are no data to compare the cefepime testing performance of BD Phoenix automated susceptibility system (BD Phoenix) and disk diffusion (DD) relative to reference broth microdilution (BMD) against carbapenemase-producing (CP

bla

KPC
-CRE) and non-producing (non-CP CRE) isolates. Cefepime susceptibility results were interpreted according to CLSI M100Ed32. Essential agreement (EA), categorical agreement (CA), minor errors (miEs), major errors (MEs), and very major errors (VMEs) were calculated for BD Phoenix (NMIC-306 Gram-negative panel) and DD relative to BMD. Correlates were also analyzed by the error rate-bounded method. EA and CA for CP

bla

KPC
-CRE isolates (
n
= 64) were <90% with BD Phoenix while among non-CP CRE isolates (
n
= 58), EA and CA were 96.6%, and 79.3%, respectively. CA was <90% with DD for both cohorts. No ME or VME was observed for either isolate cohort; however, miEs were >10% for CP

bla

KPC
-CRE and non-CP CRE with BD Phoenix and DD tests. For error rate-bounded method, miEs were <40% for I
High
+ 1 to I
Low
− 1 ranges for CP

bla

KPC
-CRE and non-CP CRE with BD Phoenix. Regarding disk diffusion, miEs were unacceptable for all MIC ranges among CP

bla

KPC
-CRE. For non-CP CRE isolates, only I
High
+ 1 to I
Low
− 1 range was acceptable at 37.2%. Using this challenge set of genotypic-phenotypic discordant CRE, the BD Phoenix MICs and DD susceptibility results trended higher (toward SDD and resistant phenotypes) relative to reference BMD results yielding lower CA. These results were more prominent among CP

bla

KPC
-CRE than non-CP CRE.
Unveiling the connection between lode gold mineralization and the metamorphic core complex evolution from the large Yangzhaiyu gold deposit, North China Craton
Authors: Li Wen-Tian , Jiang Shao-Yong 
Published: May 2024

Abstract
The Xiaoqinling gold province, located in the Neoarchean–Paleoproterozoic uplifted footwalls of the Xiaoqinling metamorphic core complex (XMCC), is one of China’s largest gold producers; however, achieving a consensus regarding their metallogenic model remains elusive. Scheelite is an indicator mineral that commonly occurs in lode gold deposits worldwide used to recognize deposit types and understand hydrothermal evolution and the origin of features. Xenotime, monazite, and rutile are common hydrothermal minerals in association with lode gold deposits worldwide. Here, we provide textual, in situ U-Pb geochronology of xenotime, monazite, and rutile, and in situ elemental and Sr-Nd isotopic compositions of scheelite within different stages from the large Yangzhaiyu lode gold deposit, aiming to elucidate its genesis and, for the first time, establish a holistic correlation between the lode gold mineralization and the evolution of the XMCC. Notably low εNd(t) values (−30.7 to −23.7), high 87Sr/86Sr ratios (0.72659–0.75914), and distinct rare earth elements, Sr, Mo, and As contents of scheelite confirm a metamorphic crustal source. Xenotime U-Pb dating and pre-ore (Stage I) scheelite reveal that ore-barren metamorphic fluids at ca. 140 Ma were oxidized with low Bi contents and buffered by greenschist facies metamorphism when the XMCC initiated. Monazite and rutile U-Pb dating combined with ore-stage scheelite geochemistry indicate a compositional shift in the more reduced auriferous metamorphic fluids, which dominated during major gold deposition periods (stages II and III) from 130 Ma to 120 Ma, characterized by significantly depleted Na and increased Bi contents. This resulted from the prograde greenschist-to-amphibolite metamorphism at mid-lower crustal depths as the result of the XMCC isostatic doming and the lithospheric mantle thinning after 130 Ma. This study highlights the crucial role of metamorphic core complexes in governing the timing, locations, and resources of the lode gold metallogenic system.
Original investigation: manipulating energy availability in male endurance runners: a randomised controlled trial
Authors: Sim Alexiaa , Tan Hui Qing , Ali Yusuf , Burns Stephen F. 
Published: May 2024

This study investigated the effect of 4 days low energy availability (LEA) on physiological markers and mood states in male endurance runners. Twelve participants (mean (standard deviation); age: 25.8 (3.8) years; fat-free mass (FFM): 52.8 (5.5) kg) completed three 4-day conditions: adequate energy availability (AEA): 45 kcal/kg FFM/day; LEA1: 30 kcal/kg FFM/day; and LEA2: 15 kcal/kg FFM/day, in a randomized order. Participants ran on a treadmill at 65% of V̇O2max until they expended 15 kcal/kg FFM/day of energy. Energy intake was adjusted to achieve the desired energy availability. Pre- and post-measurements of bone turnover, metabolism, testosterone and estradiol (plasma), resting metabolic rate (indirect calorimetry), and mood states (Brunel Mood Scale) were assessed. The results reported a significant decrease in testosterone (condition × time interaction, p = 0.03) occurred on LEA2 (Pre: 23.8 (7.0) nmol/L vs. Post: 20.3 (7.7) nmol/L) compared with AEA (Pre: 22.9 (5.5) nmol/L vs. Post: 23.3 (6.1) nmol/L) or LEA1 (Pre: 23.6 (8.6) nmol/L vs. Post: 20.9 (8.8) nmol/L). Fatigue level significantly increased (condition × time interaction, p = 0.02) in LEA2 (Pre: 3.5 (1.7) vs. Post: 6.5 (2.9)) but did not change in AEA (Pre: 2.8 (1.5) vs. Post: 2.5 (2.7)) or LEA1 (Pre: 2.8(2.4) vs. Post: 2.9 (2.0)). Other measures were unaffected by the interventions. In conclusion, this study suggests that testosterone and fatigue may serve as early indicators of LEA in male runners. However, other physiological markers and mood states appeared largely unaffected, aligning with existing literature indicating minimal disruption of physiological functions during acute LEA in male athletes. Study registration: Australian New Zealand Clinical Trials Registry (Trial No.: 381278).
A primary evaporite weld revealed in the late Paleozoic Antigonish sub-basin of Nova Scotia
Authors: Thomas Alison K. , Waldron John W.F. 
Published: May 2024

The Antigonish sub-basin lies within the late Paleozoic Maritimes Basin of Atlantic Canada. Late Devonian to early Carboniferous basin development resulted in a basin-and-range topography, within which the clastic Horton Group was deposited in grabens and half-grabens. The overlying Viséan Windsor Group contains substantial evaporite units; later basin development was accompanied by expulsion of these evaporites. In the Antigonish sub-basin, a significant stratigraphic omission surface initially described as a thrust was subsequently reinterpreted as the extensional Ainslie Detachment. This surface can be examined in drill-core, where the halite-bearing interval is reduced to 3.8 m of halite-cemented breccia of sedimentary rock fragments. The halite cement is sub-horizontally foliated and lineated. At Lakevale, an outcrop section of the Windsor Group is reduced in thickness to tens of metres. Above a basal limestone unit containing pseudomorphs of gypsum, most of the Windsor Group is represented by sedimentary-clast breccias that resemble those seen in core, but with the halite removed by solution in the near-surface environment. The stratigraphic record within the sub-basin implies that expulsion of lower Windsor salt was initially toward the edges of the basin where rising diapirs blocked the deposition of middle Windsor group, but in the basin centre a second salt unit was deposited. Subsequently, during contractional inversion of basin-bounding faults, the middle Windsor salt was expelled into diapirs near the centre of the basin. The Ainslie Detachment is reinterpreted as a primary salt weld: a boundary between units formerly above and below expelled lower Windsor evaporites. The resulting stratigraphic omissions and structures match those seen above expelled evaporite layers on continental margins.
Finslerian extension of an anisotropic strange star in the domain of modified gravity
Authors: Chowdhury Sourav Roy , Deb Debabrata , Rahaman Farook , Ray Saibal 
Published: May 2024

AbstractIn this article, we apply the Finsler spacetime to develop the Einstein field equations in the extension of modified geometry. Following Finsler geometry, which is focused on the tangent bundle with a scalar function, a scalar equation should be the field equation that defines this structure. This spacetime maintains the required causality properties on the generalized Lorentzian metric manifold. The matter field is coupled with the Finsler geometry to produce the complete action. The developed Einstein field equations are employed on the strange stellar system to improve the study. The interior of the system is composed of a strange quark matter, maintained by the MIT bag equation of state. In addition, the modified Tolman–Oppenheimer–Volkov (TOV) equation is formulated. In particular, the anisotropic stress attains the maximum at the surface. The mass-central density variation confirms the stability of the system.
Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok 
Published: May 2024

Abstract
Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC–alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs.
Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs.
The Fate(s) of CAR T-Cell Therapy: Navigating the Risks of CAR+ T-Cell Malignancy
Authors: Abou-el-Enein Mohamed 
Published: May 2024

Abstract
The introduction of chimeric antigen receptor (CAR) T-cell therapy represents a landmark advancement in treating resistant forms of cancer such as leukemia, lymphoma, and myeloma. However, concerns about long-term safety have emerged following an FDA investigation into reports of second primary malignancies (SPM) after CAR-T cell treatment. This review offers a thorough examination of how genetically modified T cells might transform into CAR+ SPM. It explores genetic and molecular pathways leading to T-cell lymphomagenesis, the balance between CAR T-cell persistence, stemness, and oncogenic risk, and the trade-off of T-cell exhaustion, which may limit therapy efficacy but potentially reduce lymphomagenesis risk.
Significance: An FDA probe into 22 cases of second primary T-cell malignancies following CAR T-cell therapy stresses the need to investigate their origins. Few may arise from preexisting genetic and epigenetic alterations and those introduced during therapeutic engineering. Technological advances, regulatory oversight, and patient monitoring are essential to mitigate potential risks.
Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension
Authors: Zafeiropoulos Stefanos , Ahmed Umair , Bekiaridou Alexandra , Jayaprakash Naveen , Mughrabi Ibrahim T. , Saleknezhad Nafiseh , Chadwick Chrystal , Daytz Anna , Kurata-Sato Izumi , Atish-Fregoso Yemil , Carroll Kaitlin , Al-Abed Yousef , Fudim Marat , Puleo Christopher , Giannakoulas George , Nicolls Mark R. , Diamond Betty , Zanos Stavros 
Published: May 2024

BACKGROUND:
Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension.

METHODS:
Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model). Animals were randomized to receive either 12-minute-long sessions of sFUS daily or sham stimulation for 14 days. Catheterizations, echocardiography, indices of autonomic function, lung and heart histology and immunohistochemistry, spleen flow cytometry, and lung single-cell RNA sequencing were performed after treatment to assess the effects of sFUS.

RESULTS:

Splenic denervation right before induction of pulmonary hypertension results in a more severe disease phenotype. In both sugen/hypoxia and monocrotaline models, sFUS treatment reduces right ventricular systolic pressure by 25% to 30% compared with sham treatment, without affecting systemic pressure, and improves right ventricular function and autonomic indices. sFUS reduces wall thickness, apoptosis, and proliferation in small pulmonary arterioles, suppresses CD3
+
and CD68
+
cell infiltration in lungs and right ventricular fibrosis and hypertrophy and lowers BNP (brain natriuretic peptide). Beneficial effects persist for weeks after sFUS discontinuation and are more robust with early and longer treatment. Splenic denervation abolishes sFUS therapeutic benefits. sFUS partially normalizes CD68
+
and CD8
+
T-cell counts in the spleen and downregulates several inflammatory genes and pathways in nonclassical and classical monocytes and macrophages in the lung. Differentially expressed genes in those cell types are significantly enriched for human pulmonary arterial hypertension–associated genes.

CONCLUSIONS:
sFUS causes dose-dependent, sustained improvement of hemodynamic, autonomic, laboratory, and pathological manifestations in 2 models of experimental pulmonary hypertension. Mechanistically, sFUS normalizes immune cell populations in the spleen and downregulates inflammatory genes and pathways in the lung, many of which are relevant in human disease.
Synthesising Diverse and Discriminatory Sets of Instances Using Novelty Search in Combinatorial Domains
Authors: Marrero Alejandro , Segredo Eduardo , León Coromoto , Hart Emma 
Published: May 2024

Abstract
Gathering sufficient instance data to either train algorithm-selection models or understand algorithm footprints within an instance space can be challenging. We propose an approach to generating synthetic instances that are tailored to perform well with respect to a target algorithm belonging to a predefined portfolio but are also diverse with respect to their features. Our approach uses a novelty search algorithm with a linearly weighted fitness function that balances novelty and performance to generate a large set of diverse and discriminatory instances in a single run of the algorithm. We consider two definitions of novelty: (1) with respect to discriminatory performance within a portfolio of solvers; (2) with respect to the features of the evolved instances. We evaluate the proposed method with respect to its ability to generate diverse and discriminatory instances in two domains (knapsack and bin-packing), comparing to another well-known quality diversity method, Multi-dimensional Archive of Phenotypic Elites (MAP-Elites) and an evolutionary algorithm that only evolves for discriminatory behaviour. The results demonstrate that the novelty search method outperforms its competitors in terms of coverage of the space and its ability to generate instances that are diverse regarding the relative size of the “performance gap” between the target solver and the remaining solvers in the portfolio. Moreover, for the Knapsack domain, we also show that we are able to generate novel instances in regions of an instance space not covered by existing benchmarks using a portfolio of state-of-the-art solvers. Finally, we demonstrate that the method is robust to different portfolios of solvers (stochastic approaches, deterministic heuristics, and state-of-the-art methods), thereby providing further evidence of its generality.
A Layered Learning Approach to Scaling in Learning Classifier Systems for Boolean Problems
Authors: Alvarez Isidro M. , Nguyen Trung B. , Browne Will N. , Zhang Mengjie 
Published: May 2024

Abstract
Evolutionary Computation (EC) often throws away learned knowledge as it is reset for each new problem addressed. Conversely, humans can learn from small-scale problems, retain this knowledge (plus functionality), and then successfully reuse them in larger-scale and/or related problems. Linking solutions to problems has been achieved through layered learning, where an experimenter sets a series of simpler related problems to solve a more complex task. Recent works on Learning Classifier Systems (LCSs) has shown that knowledge reuse through the adoption of Code Fragments, GP-like tree-based programs, is plausible. However, random reuse is inefficient. Thus, the research question is how LCS can adopt a layered-learning framework, such that increasingly complex problems can be solved efficiently. An LCS (named XCSCF*) has been developed to include the required base axioms necessary for learning, refined methods for transfer learning and learning recast as a decomposition into a series of subordinate problems. These subordinate problems can be set as a curriculum by a teacher, but this does not mean that an agent can learn from it; especially if it only extracts over-fitted knowledge of each problem rather than the underlying scalable patterns and functions. Results show that from a conventional tabula rasa, with only a vague notion of which subordinate problems might be relevant, XCSCF* captures the general logic behind the tested domains and therefore can solve any n-bit Multiplexer, n-bit Carry-one, n-bit Majority-on, and n-bit Even-parity problems. This work demonstrates a step towards continual learning as learned knowledge is effectively reused in subsequent problems.