bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental Fatigue: The Cost of Cognitive Loading on Weight Lifting, Resistance Training, and Cycling Performance
Authors: Staiano Walter , Bonet Lluis Raimon Salazar , Romagnoli Marco , Ring Christopher 
Published: March 2023

Purpose: Mental fatigue (MF) can impair physical performance in sport. We tested the hypothesis that cognitive load alone, and intermixed with standard resistance training, would induce MF, increase rating of perceived exertion (RPE), alter perception of weight lifting and training, and impair cycling time-trial performance. Methods: This 2-part study employed a within-participant design. In part 1, after establishing leg-extension 1-repetition maximum (1RM), 16 participants lifted and briefly held weights at 20%, 40%, 60%, and 80% of 1RM. RPE and electromyography (EMG) were measured for each lift. During the testing sessions, participants completed cognitive tasks (MF condition) or watched neutral videos (control condition) for 90 minutes before lifting the weights. In part 2, they completed submaximal resistance training comprising 6 weight training exercises followed by a 20-minute cycling time trial. In the MF condition, they completed cognitive tasks before and between weight training exercises. In the control condition, they watched neutral videos. Mood (Brunel Mood Scale), workload (National Aeronautics and Space Administration Task Load Index), MF-visual analogue scale (MF-VAS), RPE, psychomotor vigilance, distance cycled, power output, heart rate, and blood lactate were measured. Results: In part 1, the cognitive task increased lift-induced RPE (P = .011), increased MF-VAS (P = .002), and altered mood (P < .001) compared with control. EMG did not differ between conditions. In part 2, the cognitive tasks increased RPE (P < .001), MF-VAS (P < .001), and mental workload (P < .001), but reduced cycling time-trial power (P = .032) and distance (P = .023) compared with control. Heart rate and blood lactate did not differ between conditions. Conclusion: A state of MF induced by cognitive load, alone or intermixed with physical load, increased RPE during weight lifting and training and impaired subsequent cycling performance.
Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis
Authors: Joshi Gaurav , Arthur Nancy Beryl Janet , Geetha Thenral S , Datari Phaneendra Venkateswara Rao , Modak Kirti , Roy Debanjan , Chaudhury Anurag Dutta , Sundaraganesan Prasanth , Priyanka Sweety , NA Fouzia , Ramprasad Vedam , Abraham Aby , Srivastava Vivi M , Srivastava Alok , Kulkarni Uday Prakash , George Biju , Velayudhan Shaji R 
Published: March 2023

BackgroundFanconi anaemia (FA) is a rare inherited bone marrow failure disease caused by germline pathogenic variants in any of the 22 genes involved in the FA-DNA interstrand crosslink (ICL) repair pathway. Accurate laboratory investigations are required for FA diagnosis for the clinical management of the patients. We performed chromosome breakage analysis (CBA), FANCD2 ubiquitination (FANCD2-Ub) analysis and exome sequencing of 142 Indian patients with FA and evaluated the efficiencies of these methods in FA diagnosis.MethodsWe performed CBA and FANCD2-Ub analysis in the blood cells and fibroblasts of patients with FA. Exome sequencing with improved bioinformatics to detect the single number variants and CNV was carried out for all the patients. Functional validation of the variants with unknown significance was done by lentiviral complementation assay.ResultsOur study showed that FANCD2-Ub analysis and CBA on peripheral blood cells could diagnose 97% and 91.5% of FA cases, respectively. Exome sequencing identified the FA genotypes consisting of 45 novel variants in 95.7% of the patients with FA.FANCA(60.2%),FANCL(19.8%) andFANCG(11.7%) were the most frequently mutated genes in the Indian population. AFANCLfounder mutation c.1092G>A; p.K364=was identified at a very high frequency (~19%) in our patients.ConclusionWe performed a comprehensive analysis of the cellular and molecular tests for the accurate diagnosis of FA. A new algorithm for rapid and cost-effective molecular diagnosis for~90% of FA cases has been established.
Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial
Authors: Ilfeld Brian M , Khatibi Bahareh , Maheshwari Kamal , Madison Sarah , Ali Sakr Esa Wael , Mariano Edward R , Kent Michael , Hanling Steven , Sessler Daniel I , Eisenach James C , Cohen Steven P , Mascha Edward , Li Shuyi , Turan Alparslan 
Published: March 2023

IntroductionWe previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design.MethodsThe original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale.ResultsAmong patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p<0.001) for average and 25% (p<0.001) for worst pain in patients given a placebo infusion. At 4 weeks, the percentage of participants rating their pain as improved was 53% for the active vs 30% for the placebo groups (95% CI 1.7 (1.1, 2.7), p=0.008). For all patients combined, the median (IQR) phantom pain Numeric Rating Scale improvements at 4 weeks considered small, medium, and large were 2 (0–2), 3 (2–5), and 5 (3–7), respectively. The median improvements in the Brief Pain Inventory interference subscale (0–70) associated with small, medium, and large analgesic changes were 8 (1–18), 22 (14–31), and 39 (26–47).ConclusionsAmong patients with postamputation phantom pain, a continuous peripheral nerve block more than doubles the chance of a clinically relevant improvement in pain intensity. Amputees with phantom and/or residual limb pain rate analgesic improvements as clinically relevant similarly to other chronic pain etiologies, although their smallest relevant improvement in the Brief Pain Inventory was significantly larger than previously published values.Trial registration numberNCT01824082.
Global Interconnect Optimization
Authors: Daboul Siad , Held Stephan , Natura Bento , Rotter Daniel 
Published: March 2023

We propose a new comprehensive solution to global interconnect optimization. Traditional buffering algorithms mostly insert repeaters on a net-by-net basis based on slacks and possibly guided by global wires.
We show how to integrate routing congestion, placement congestion, global timing constraints, power consumption, and additional constraints into a single resource sharing formulation. The core of our algorithm is a new buffered routing subroutine. Given a net and Lagrangean resource prices for routing, timing, placement, and power, it computes a buffered Steiner tree. The resource sharing framework provides a special multiplicative price update for fast convergence.
Our algorithm is fast enough for practical instances. We demonstrate experimentally on 7nm microprocessor units that it significantly improves timing while reducing netlength and power consumption in an industrial design flow. Our implementation scales well under parallelization with up to 128 threads.
Factors Impacting Diversity and Effectiveness of Evolved Modular Robots
Authors: Pigozzi Federico , Medvet Eric , Bartoli Alberto , Rochelli Marco 
Published: March 2023

In many natural environments, different forms of living organisms successfully accomplish the same task while being diverse in shape and behavior. This biodiversity is what made life capable of adapting to disrupting changes. Being able to reproduce biodiversity in artificial agents, while still optimizing them for a particular task, might increase their applicability to scenarios where human response to unexpected changes is not possible. In this work, we focus onVoxel-based Soft Robots(VSRs), a form of robots that grants great freedom in the design of both morphology and controller and is hence promising in terms of biodiversity. We useevolutionary computationfor optimizing, at the same time, morphology and controller of VSRs for the task of locomotion. We investigate experimentally whether three key factors—representation, Evolutionary Algorithm (EA), and environment—impact the emergence of biodiversity and if this occurs at the expense of effectiveness. We devise an automatic machine learning pipeline for systematically characterizing the morphology and behavior of robots resulting from the optimization process. We classify the robots into species and then measure biodiversity in populations of robots evolved in a multitude of conditions resulting from the combination of different morphology representations, controller representations, EAs, and environments. The experimental results suggest that, in general, EA and environment matter more than representation. We also propose a novel EA based on a speciation mechanism that operates on morphology and behavior descriptors and we show that it allows to jointly evolve morphology and controller of effective and diverse VSRs.
Evaluation of Four Malaria Rapid Diagnostic Test Kits Used at the Enyiresi Government Hospital in the Eastern Region of Ghana
Authors: Domfeh Seth A. , Darkwa Boateng Y. , Gablah Raymond K. , Adu-Asamoah Evans , Obirikorang Christian 
Published: March 2023

Microscopic identification of Plasmodium spp. is the gold standard for malaria diagnosis. However, malaria rapid diagnostic test kits are also available for prompt diagnosis. This study evaluated four routinely used malaria rapid diagnostic test kits at the Enyiresi Government Hospital in the Eastern Region of Ghana. This cross-sectional study was conducted among 238 patients suspected of malaria. Venous blood samples were collected to identify Plasmodium falciparum using microscopic techniques. Further, the performances of four malaria rapid diagnostic test kits, First Response Malaria Ag Pf, Carestart Malaria Pf, SD Bioline Ag Pf, and ABON Malaria Pf, were evaluated using the results from the microscopy as the standard reference. As confirmed by microscopy, 65.5% (156/238) of the patients have falciparum malaria. All malaria rapid diagnostic test kits had sensitivities and specificities over 75% compared to microscopy results as the reference standard. However, the SD Bioline Ag Pf kit recorded the highest agreement with the microscopy (

Cohe
n
’
s

kappa
=
0.879

). All the malaria rapid diagnostic test kits performed quite well and can be used in emergencies. However, results from these kits need to be confirmed by microscopy.
Minimal Residual Disease Data in Hematologic Malignancy Drug Applications and Labeling: An FDA Perspective
Authors: Baines Andrea C. , Yazdy Maryam Sarraf , Kasamon Yvette L. , Ershler Rachel , Jen Emily Y. , Kanapuru Bindu , Richardson Nicholas C. , Lane Ashley , Carioti Theresa , Theoret Marc R. , Pazdur Richard , Gormley Nicole J. 
Published: March 2023

Abstract
Minimal residual disease (MRD) is increasingly used as a prognostic biomarker, a measure of clinical efficacy, and a guide for treatment decisions in various hematologic malignancies. We sought to characterize MRD data in registrational trials in hematologic malignancies submitted to the U.S. Food and Drug Administration (FDA) with the ultimate goal of expanding the utility of MRD data in future drug applications. We descriptively analyzed MRD data collected in registrational trials, including the type of MRD endpoint, assay, disease compartment(s) assessed, and the acceptance of MRD data in the U.S. prescribing information (USPI). Of 196 drug applications submitted between January 2014 and February 2021, 55 (28%) included MRD data. Of the 55 applications, MRD data was proposed by the Applicant for inclusion in the USPI in 41 (75%) applications but was included in only 24 (59%). Despite an increasing number of applications that proposed to include MRD data in the USPI, the acceptance rate decreased over time. Although MRD data have the potential to expedite drug development, our analysis identified challenges and specific areas for improvement, including assay validation, standardization of collection methods to optimize performance, and considerations in trial design and statistical methodology.
Structurally Complex Osteosarcoma Genomes Exhibit Limited Heterogeneity within Individual Tumors and across Evolutionary Time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew V. , Cam Maren , Gross Amy C. , Raphael Benjamin J. , Roberts Ryan D. 
Published: March 2023

Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNA) are the genetic drivers of disease. Models around genomic instability conflict—it is unclear whether osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization of the fitness landscape or an early catastrophic event followed by stable maintenance of an abnormal genome. We address this question by investigating SCNAs in &gt;12,000 tumor cells obtained from human osteosarcomas using single-cell DNA sequencing, with a degree of precision and accuracy not possible when inferring single-cell states using bulk sequencing. Using the CHISEL algorithm, we inferred allele- and haplotype-specific SCNAs from this whole-genome single-cell DNA sequencing data. Surprisingly, despite extensive structural complexity, these tumors exhibit a high degree of cell-cell homogeneity with little subclonal diversification. Longitudinal analysis of patient samples obtained at distant therapeutic timepoints (diagnosis, relapse) demonstrated remarkable conservation of SCNA profiles over tumor evolution. Phylogenetic analysis suggests that the majority of SCNAs were acquired early in the oncogenic process, with relatively few structure-altering events arising in response to therapy or during adaptation to growth in metastatic tissues. These data further support the emerging hypothesis that early catastrophic events, rather than sustained genomic instability, give rise to structural complexity, which is then preserved over long periods of tumor developmental time.Significance:Chromosomally complex tumors are often described as genomically unstable. However, determining whether complexity arises from remote time-limited events that give rise to structural alterations or a progressive accumulation of structural events in persistently unstable tumors has implications for diagnosis, biomarker assessment, mechanisms of treatment resistance, and represents a conceptual advance in our understanding of intratumoral heterogeneity and tumor evolution.
Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells
Authors: Yang Chunsong , Wierbiłowicz Krzysztof , Dworak Natalia M. , Bae Song Yi , Tengse Sachi B. , Abianeh Nicki , Drake Justin M. , Abbas Tarek , Ratan Aakrosh , Wotton David , Paschal Bryce M. 
Published: March 2023

The ADP-ribosyltransferase PARP7 modulates protein function by conjugating ADP-ribose to the side chains of acceptor amino acids. PARP7 has been shown to affect gene expression in prostate cancer cells and certain other cell types by mechanisms that include transcription factor ADP-ribosylation. Here, we use a recently developed catalytic inhibitor to PARP7, RBN2397, to study the effects of PARP7 inhibition in androgen receptor (AR)-positive and AR-negative prostate cancer cells. We find that RBN2397 has nanomolar potency for inhibiting androgen-induced ADP-ribosylation of the AR. RBN2397 inhibits the growth of prostate cancer cells in culture when cells are treated with ligands that activate the AR, or the aryl hydrocarbon receptor, and induce PARP7 expression. We show that the growth-inhibitory effects of RBN2397 are distinct from its enhancement of IFN signaling recently shown to promote tumor immunogenicity. RBN2397 treatment also induces trapping of PARP7 in a detergent-resistant fraction within the nucleus, which is reminiscent of how inhibitors such as talazoparib affect PARP1 compartmentalization. Because PARP7 is expressed in AR-negative metastatic tumors and RBN2397 can affect cancer cells through multiple mechanisms, PARP7 may be an actionable target in advanced prostate cancer.Significance:RBN2397 is a potent and selective inhibitor of PARP7 that reduces the growth of prostate cancer cells, including a model for treatment-emergent neuroendocrine prostate cancer. RBN2397 induces PARP7 trapping on chromatin, suggesting its mechanism of action might be similar to clinically used PARP1 inhibitors.
Urine Cell Transcriptomes Implicate Specific Renal Inflammatory Pathways Associated With Difficult‐to‐Control Hypertension
Authors: Umanath Kausik , She Ruicong , Hassett Clare , Adrianto Indra , Levin Albert M. , Savickas Gina , Yee Jerry , Ortiz Pablo 
Published: March 2023

Background
The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first‐morning urine samples from individuals who were hypertensive who exhibited difficult‐to‐control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome‐wide associations with BP. We also analyzed nephron‐specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult‐to‐control hypertension.

Methods and Results

Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first‐morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP‐difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy‐to‐control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2‐fold change in the BP‐difficult group. In BP‐difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76;
P
=0.006) and Serpin Family B Member 9 (fold change, 5.10;
P
=0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP‐difficult group (
P
<0.001).

Conclusions
We conclude that transcriptomes from cells shed in first‐morning urine identify a gene expression profile in difficult‐to‐control hypertension that associates with renal inflammation.
Diabetes Induces Cardiac Fibroblast Activation, Promoting a Matrix‐Preserving Nonmyofibroblast Phenotype, Without Stimulating Pericyte to Fibroblast Conversion
Authors: Alex Linda , Tuleta Izabela , Hanna Anis , Frangogiannis Nikolaos G. 
Published: March 2023

Background
Interstitial and perivascular fibrosis may contribute to diabetes‐associated heart failure. Pericytes can convert to fibroblasts under conditions of stress and have been implicated in the pathogenesis of fibrotic diseases. We hypothesized that in diabetic hearts, pericytes may convert to fibroblasts, contributing to fibrosis and to the development of diastolic dysfunction.

Methods and Results

Using pericyte:fibroblast dual reporter (NG2
Dsred
[neuron‐glial antigen 2 red fluorescent protein variant]; PDGFRα
EGFP
[platelet‐derived growth factor receptor alpha enhanced green fluorescent protein]) mice in a type 2 diabetic db/db background, we found that diabetes does not significantly affect pericyte density but reduces the myocardial pericyte:fibroblast ratio. Lineage tracing using the inducible NG2
CreER
driver, along with reliable labeling of fibroblasts with the PDGFRα reporter system, showed no significant pericyte to fibroblast conversion in lean and db/db hearts. In addition, db/db mouse cardiac fibroblasts did not undergo myofibroblast conversion and had no significant induction of structural collagens but exhibited a matrix‐preserving phenotype, associated with increased expression of antiproteases, matricellular genes, matrix cross‐linking enzymes, and the fibrogenic transcription factor
cMyc
. In contrast, db/db mouse cardiac pericytes had increased expression of
Timp3
, without any changes in expression of other fibrosis‐associated genes. The matrix‐preserving phenotype of diabetic fibroblasts was associated with induction of genes encoding oxidative (
Ptgs2
/cycloxygenase‐2, and
Fmo2
) and antioxidant proteins (
Hmox1
,
Sod1
). In vitro, high glucose partially recapitulated the in vivo changes in diabetic fibroblasts.

Conclusions
Diabetic fibrosis is not mediated through pericyte to fibroblast conversion but involves acquisition of a matrix‐preserving fibroblast program, which is independent of myofibroblast conversion and is only partially explained by the effects of the hyperglycemic environment.
Association of Thoracic Aortic Aneurysm Versus Aortic Dissection on Outcomes After Thoracic Endovascular Aortic Repair
Authors: Hasan Irsa S. , Brown James A. , Serna‐Gallegos Derek , Aranda‐Michel Edgar , Yousef Sarah , Wang Yisi , Sultan Ibrahim 
Published: March 2023

Background
Because thoracic endovascular aortic repair (TEVAR) has become the standard of care for complicated type B aortic dissection (TBAD) and descending thoracic aortic (DTA) aneurysm, it is important to understand outcomes and use of TEVAR across thoracic aortic pathologies.

Methods and Results

This was an observational study of patients with TBAD or DTA undergoing TEVAR from 2010 to 2018, using the Nationwide Readmissions Database. In‐hospital mortality, postoperative complications, admission costs, and 30‐ and 90‐day readmissions were compared between the groups. Mixed model logistic regression was used to identify variables associated with mortality. An estimated total of 12 824 patients underwent TEVAR nationally, of which 6043 had an indication of TBAD and 6781 of DTA. Patients with aneurysms were more likely to be older, women, have cardiovascular disease, and have chronic pulmonary disease compared with patients with TBAD. Weighted in‐hospital mortality was higher for TBAD (8% [1054/12 711] versus 3% [433/14 407],
P
<0.001), compared with DTA, as were all postoperative complications. Patients with TBAD had a higher cost of care during their index admission (57.3 versus 38.8 × $1000,
P
<0.001), compared with DTA. The 30‐day and 90‐day weighted readmissions were more frequent for the TBAD group compared with DTA (20% [1867/12 711] and 30% [2924/12 711] versus 15% [1603/14 407] and 25% [2695/14 407], respectively,
P
<0.001). On multivariable adjustment, TBAD was independently associated with mortality (odds ratio, 2.06 [95% CI, 1.68–2.52];
P
<0.001).

Conclusions
After TEVAR, patients who presented with TBAD had higher rates of postoperative complications, in‐hospital mortality, and cost compared with DTA. The incidence of early readmission was substantial for patients undergoing TEVAR, faring worse for those undergoing TEVAR for TBAD as compared with DTA.