bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Visual Analog Scale for Self-Reported Quality of Life
Authors: Redford Elizabeth , Heuer Sabine 
Published: September 2023

Purpose:
People with dementia (PWD) are one of the fastest-growing clinical populations for speech-language pathologists. Self-reported quality of life (QoL) assessments are critical patient-reported outcome measures that align with person-centered care principles. However, proxy-reporting is most often used due to assumptions that PWD cannot provide reliable self-report. Visual analog scales (VASs) have been successfully used with people with expressive and cognitive deficits to measure subjective constructs such as QoL, mood, and pain. The purpose of this project is to evaluate the feasibility and reliability of a VAS QoL assessment tool.

Methods:
Twenty older adults free of cognitive impairment were assessed using the quality of life in Alzheimer’s disease (QoL-AD) and the QoL-AD in combination with a VAS (VAS QoL-AD). The construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD were assessed by performing both assessments twice, 4 weeks apart.

Results:
Significant correlations between the overall VAS QoL-AD and the QoL-AD scale ratings, between most of the QoL-AD and VAS QoL-AD subtests, and between the first and second assessment scores were observed.

Conclusions:
Results indicated strong construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD in people without dementia. These results warrant further research into the development of a dementia-specific, self-reported VAS QoL scale for PWD.
Gender, Pain, and Function Associated With Physical Activity After Hospitalization in Persons Living With Dementia
Authors: Kuzmik Ashley , Boltz Marie , Resnick Barbara , Drazich Brittany F. , Galvin James E. 
Published: September 2023

Background:
The purpose of this study was to identify factors that are associated with physical activity after hospitalization in persons living with dementia.

Methods:
Multiple linear regressions were conducted to test factors associated with objective activity levels (sedentary, low, moderate, and vigorous) among 244 patients living with dementia from a randomized controlled trial.

Results:
Within 48 hours of hospital discharge, time in sedentary behavior was associated with increased pain (β=0.164, P=0.015). Time in low activity was associated with less pain (β=−0.130, P=0.049) and higher physical function (β=0.300, P=<0.001). Time in moderate activity was associated with increased physical function (β=0.190, P=0.008) and male gender (β=0.155, P=0.016). No significant associations of potential factors were found with time in vigorous activity.

Conclusions:
Our findings suggest that managing or reducing pain, encouraging individual functional level, and gender could influence time spent in physical activity after acute hospitalization in persons living with dementia.
National Multi-Institutional Validation of a Surgical Transfusion Risk Prediction Model
Authors: Lou Sunny S , Liu Yaoming , Cohen Mark E , Ko Clifford Y , Hall Bruce L , Kannampallil Thomas 
Published: September 2023

BACKGROUND:
Accurate estimation of surgical transfusion risk is important for many aspects of surgical planning, yet few methods for estimating are available for estimating such risk. There is a need for reliable validated methods for transfusion risk stratification to support effective perioperative planning and resource stewardship.

STUDY DESIGN:
This study was conducted using the American College of Surgeons NSQIP datafile from 2019. S-PATH performance was evaluated at each contributing hospital, with and without hospital-specific model tuning. Linear regression was used to assess the relationship between hospital characteristics and area under the receiver operating characteristic (AUROC) curve.

RESULTS:
A total of 1,000,927 surgical cases from 414 hospitals were evaluated. Aggregate AUROC was 0.910 (95% CI 0.904 to 0.916) without model tuning and 0.925 (95% CI 0.919 to 0.931) with model tuning. AUROC varied across individual hospitals (median 0.900, interquartile range 0.849 to 0.944), but no statistically significant relationships were found between hospital-level characteristics studied and model AUROC.

CONCLUSIONS:
S-PATH demonstrated excellent discriminative performance, although there was variation across hospitals that was not well-explained by hospital-level characteristics. These results highlight the S-PATH’s viability as a generalizable surgical transfusion risk prediction tool.
Pyruvate dehydrogenase kinase expression profile is a biomarker for cancer sensitivity to dichloroacetate-mediated growth inhibition
Authors: Gang Bevan P , Rooke Melissa , Sun Ramon C , Banskota Samagya , Mishra Sheenu , Dahlstrom Jane E , Blackburn Anneke C 
Published: September 2023

AbstractBackgroundCancer cells favour glycolysis and lactate production over mitochondrial metabolism despite the presence of oxygen (the Warburg effect). Increased pyruvate dehydrogenase kinase (PDK) activity contributes to this glycolytic phenotype. Dichloroacetate (DCA) is a PDK inhibitor with anti-cancer potential that inhibits all four isoforms of PDK but with differing potencies, thus expression of different isoforms may determine sensitivity to DCA.MethodsThe association of sensitivity to growth inhibition by DCA, on-target effects of DCA and expression of all four isoforms of PDKs in a range of epithelial cancer cell lines was investigatedin vitroandin vivo.ResultsDCA inhibited growth of cancer cellsin vivoandin vitro,reduced pyruvate dehydrogenase phosphorylation and reduced lactate production. The magnitude of the effect of DCA on growth was variable and correlated with the PDK expression profiles of the cells, with low expression of PDK3 (highest Kifor DCA) conferring the highest sensitivity towards DCA. PDK2 siRNA-knockdown inhibited growth to a similar extent to DCA, whilst PDK3 knockdown significantly increased sensitivity to DCA.ConclusionThe PDK expression profile is a potential biomarker for sensitivity to DCA, and should be considered when translating PDK inhibitors into clinical use.
Testing Adaptive Therapy Protocols using Gemcitabine and Capecitabine on a Mouse Model of Endocrine-Resistant Breast Cancer
Authors: Seyedi Sareh , Teo Ruthanne , Foster Luke , Saha Daniel , Mina Lida , Northfelt Donald , Anderson Karen S. , Shibata Darryl , Gatenby Robert , Cisneros Luis , Troan Brigid , Anderson Alexander R. A. , Maley Carlo C. 
Published: September 2023

ABSTRACTHighly effective cancer therapies often face limitations due to acquired resistance and toxicity. Adaptive therapy, an ecologically inspired approach, seeks to control therapeutic resistance and minimize toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life over maximum cell kill. In preparation for a clinical trial in breast cancer, we used large populations of MCF7 cells to rapidly generate endocrine-resistance breast cancer cell line. We then mimicked second line therapy in ER+ breast cancers by treating the endocrine-resistant MCF7 cells in a mouse xenograft model to test adaptive therapy with capecitabine, gemcitabine, or the combination of those two drugs. Dose-modulation adaptive therapy with capecitabine alone increased survival time relative to MTD, but not statistically significant (HR: 0.22, 95% CI 0.043-1.1 P = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI: 0.024 - 0.55, P = 0.007) and intermittent adaptive therapies significantly increased survival time compared to high dose combination therapy (HR = 0.07, 95% CI: 0.013 - 0.42; P = 0.003). Overall, survival time increased with reduced dose for both single drugs (P < 0.01) and combined drugs (P < 0.001). Adaptive therapy protocols resulted in tumors with lower proportions of proliferating cells (P = 0.0026) and more apoptotic cells (P = 0.045). The results show that Adaptive therapy outperforms high-dose therapy in controlling endocrine-resistant breast cancer, favoring slower-growing tumors, and showing promise in two-drug alternating regimens.
Enhancing Luciferase Activity and Stability through Generative Modeling of Natural Enzyme Sequences
Authors: Xie Wen Jun , Liu Dangliang , Wang Xiaoya , Zhang Aoxuan , Wei Qijia , Nandi Ashim , Dong Suwei , Warshel Arieh 
Published: September 2023

AbstractThe availability of natural protein sequences synergized with generative artificial intelligence (AI) provides new paradigms to create enzymes. Although active enzyme variants with numerous mutations have been produced using generative models, their performance often falls short compared to their wild-type counterparts. Additionally, in practical applications, choosing fewer mutations that can rival the efficacy of extensive sequence alterations is usually more advantageous. Pinpointing beneficial single mutations continues to be a formidable task. In this study, using the generative maximum entropy model to analyzeRenillaluciferase homologs, and in conjunction with biochemistry experiments, we demonstrated that natural evolutionary information could be used to predictively improve enzyme activity and stability by engineering the active center and protein scaffold, respectively. The success rate of designed single mutants is ∼50% to improve either luciferase activity or stability. These finding highlights nature’s ingenious approach to evolving proficient enzymes, wherein diverse evolutionary pressures are preferentially applied to distinct regions of the enzyme, ultimately culminating in an overall high performance. We also reveal an evolutionary preference inRenillaluciferase towards emitting blue light that holds advantages in terms of water penetration compared to other light spectrum. Taken together, our approach facilitates navigation through enzyme sequence space and offers effective strategies for computer-aided rational enzyme engineering.
Neurorehabilitation of the upper extremity – Immersive virtual reality vs. robot-assisted training. A comparative study
Authors: Lülsdorff Kira , Junker Frederick Benjamin , Studer Bettina , Wittenberg Heike , Pickenbrock Heidrun , Schmidt-Wilcke Tobias 
Published: September 2023

AbstractBackgroundSevere paresis of the contralesional upper extremity is one of the most common and debilitating post-stroke impairments. The need for cost-effective high-intensity training is driving the development of new technologies, which can complement and extent conventional therapies. Apart from established methods using robotic devices, immersive virtual reality (iVR) systems hold promise to provide cost-efficient high-intensity arm training.ObjectiveWe investigated whether iVR-based arm training yields at least equivalent effects on upper extremity function as compared to a robot-assisted training in stroke patients with severe arm paresis.Methods52 stroke patients with severe arm paresis received a total of ten daily group therapy sessions over a period of three weeks, which consisted of 20 minutes of conventional therapy and 20 minutes of either robot-assisted (ARMEOSpring®) or iVR-based (CUREO®) arm training. Changes in upper extremity function was assessed using the Action Research Arm Test (ARAT) and user acceptance was measured with the User Experience Questionnaire (UEQ).ResultsiVR-based training was not inferior to robot-assisted training. We found that 84% of patients treated with iVR and 50% of patients treated with robot-assisted arm training showed a clinically relevant improvement of upper extremity function. This difference could neither be attributed to differences between the groups regarding age, gender, duration after stroke, affected body side or ARAT scores at baseline, nor to differences in the total amount of therapy provided.ConclusionThe present study results show that iVR-based arm training seems to be a promising addition to conventional therapy. Potential mechanisms by which iVR unfolds its effects are discussed.Registry numberDRKS00032489
Comparison of Inter-Joint Coordination Strategies during Activities of Daily Living with Prosthetic and Anatomical Limbs
Authors: Lee Christina , Gates Deanna 
Published: September 2023

AbstractWhile healthy individuals have redundant degrees of freedom of the joints, they coordinate their multi-joint movements such that the redundancy is effectively reduced. Achieving high inter-joint coordination may be difficult for upper limb prosthesis users due to the lack of proprioceptive feedback and limited motion of the terminal device. This study compared inter-joint coordination between prosthesis users and individuals without limb loss during different upper limb activities of daily living (ADLs). Nine unilateral prosthesis users (five males) and nine age- and sex-matched controls without limb loss completed three unilateral and three bilateral ADLs. Principal component analysis was applied to the three-dimensional motion trajectories of the trunk and arms to identify coordinative patterns. For each ADL, we quantified the cumulative variance accounted for (VAF) of the first five principal components (pcs), which was the lowest number of pcs that could achieve 90% VAF in control limb movements across all ADLs (5 < n < 9). The VAF was lower for movements involving a prosthesis compared to those completed by controls across all ADLs (p < 0.001). The pc waveforms were similar between movements involving a prosthesis and movements completed by control participants for pc1 (r > 0.78, p < 0.001). The magnitude of the relationship for pc2 and pc3 differed between ADLs, with the strongest correlation for symmetric bilateral ADLs (0.67 < r < 0.97, p < 0.001). Collectively, this study demonstrates that activities of daily living are less coordinated for prosthesis users compared to individuals without limb loss. Future work should explore how device features, such as the availability of sensory feedback or motorized wrist joints influence multi-joint coordination.
Development of a Neoadjuvant Treatment Pathway to Standardize Pancreatic Cancer Care and Improve Outcomes Across a Large Diverse Health System
Authors: Parakrama Ruwan , Sidiqi Baho U. , Demyan Lyudmyla , Standring Oliver , Cooper Dylan J. , Pasha Shamsher , Pinto Danielle M , Zavadsky Tiffany , Zou Xianghui , Patruni Sunita , Kapusta Adrianna , Nosrati Jason , Tchelebi Leila T. , Weiss Matthew J. , Herman Joseph M. , King Daniel A. 
Published: September 2023

AbstractBackgroundManagement of localized pancreatic cancer is variable. We describe the development of a neoadjuvant therapy pathway (NATP) to standardize care across a large healthcare system.MethodsWe conducted an IRB-approved retrospective analysis of NATP patients between June 2019 and March 2022. The primary endpoint was NATP completion, and secondary endpoints included overall survival (OS) and quality measures.ResultsFifty-nine patients began NATP, median age 70, locally advanced 44.1%. Median time on NATP was 6.1 months. The initial chemotherapy was FOLFIRINOX (64.2%) and gemcitabine/nab-paclitaxel (GnP; (35.6%)) followed by radiation in 32 (54.2%) patients. Forty-four (74.6%) completed the NATP and 30 (50.8%) underwent surgical exploration with 86.7% undergoing successful resection (61.5% R0, 23.1% R1) while 14 remained unresectable. NATP completion was associated with increased likelihood of resection (p<0.001). At median follow-up of 13.4 months, median OS was 20.9 months (95% CI 13.3- 28.5) and 1- and 2-year OS was 82.5% and 49.7%. NATP completion resulted in improved OS with median OS not reached and 1- and 2-year OS of 89.7% and 59.4% (p=0.004). Median time to NATP start was 20 days after MDR and median time to surgery was 35 days. Age, ECOG, surgical stage, chemotherapy regimen and NATP completion were significant univariable predictors of OS with ECOG status remaining significant on multivariable analysis.ConclusionOur outcomes provide a baseline for future guidance in improving care across a large system. Efforts to complete NATP and improve patient ECOG may result in more patients undergoing surgery and improve survival.
Rare variation in noncoding regions with evolutionary signatures contributes to autism spectrum disorder risk
Authors: Shin Taehwan , Song Janet H.T. , Kosicki Michael , Kenny Connor , Beck Samantha G. , Kelley Lily , Qian Xuyu , Bonacina Julieta , Papandile Frances , Antony Irene , Gonzalez Dilenny , Scotellaro Julia , Bushinsky Evan M. , Andersen Rebecca E. , Maury Eduardo , Pennacchio Len A. , Doan Ryan N. , Walsh Christopher A. 
Published: September 2023

AbstractLittle is known about the role of noncoding regions in the etiology of autism spectrum disorder (ASD). We examined three classes of noncoding regions: Human Accelerated Regions (HARs), which show signatures of positive selection in humans; experimentally validated neural Vista Enhancers (VEs); and conserved regions predicted to act as neural enhancers (CNEs). Targeted and whole genome analysis of >16,600 samples and >4900 ASD probands revealed that likely recessive, rare, inherited variants in HARs, VEs, and CNEs substantially contribute to ASD risk in probands whose parents share ancestry, which enriches for recessive contributions, but modestly, if at all, in simplex family structures. We identified multiple patient variants in HARs nearIL1RAPL1and in a VE nearSIM1and showed that they change enhancer activity. Our results implicate both human-evolved and evolutionarily conserved noncoding regions in ASD risk and suggest potential mechanisms of how changes in regulatory regions can modulate social behavior.
Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions
Authors: Yoshimura Saori , Shimada Ryuki , Kikuchi Koji , Kawagoe Soichiro , Abe Hironori , Iisaka Sakie , Fujimura Sayoko , Yasunaga Kei-ichiro , Usuki Shingo , Tani Naoki , Ohba Takashi , Kondoh Eiji , Saio Tomohide , Araki Kimi , Ishiguro Kei-ichiro 
Published: September 2023

ABSTRACTMeiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identified HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyses and single-cell RNA-sequencing demonstrated that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress. Chromatin binding analysisin vivoand DNA-binding assaysin vitrosuggested that HSF5 binds to promoters in a subset of genes associated with chromatin organization. HSF5 recognizes a DNA motif different from typical heat shock elements recognized by other canonical HSFs. This study suggests that HSF5 is an atypical HSF that enforces the gene expression program for pachytene transition during meiotic prophase in males.
Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors
Authors: van Belzen Ianthe A.E.M. , van Tuil Marc , Badloe Shashi , Janse Alex , Verwiel Eugène T.P. , Santoso Marcel , de Vos Sam , Baker-Hernandez John , Kerstens Hindrik H.D. , Solleveld-Westerink Nienke , Meister Michael T. , Drost Jarno , van den Heuvel-Eibrink Marry M. , Merks Johannes H. M. , Molenaar Jan J. , Peng Weng Chuan , Tops Bastiaan B.J. , Holstege Frank C.P. , Kemmeren Patrick , Hehir-Kwa Jayne Y. 
Published: September 2023

AbstractBackgroundIn pediatric cancer, structural variants (SVs) and copy number alterations can contribute to cancer initiation and progression, and hence aid diagnosis and treatment stratification. The few studies into complex rearrangements have found associations with tumor aggressiveness or poor outcome. Yet, their prevalence and biological relevance across pediatric solid tumors remains unknown.ResultsIn a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy and chromothripsis across five pediatric solid cancer types: neuroblastoma, Ewing sarcoma, Wilms tumor, hepatoblastoma and rhabdomyosarcoma. Complex SVs were identified in 56 tumors (47%) and different classes occurred across multiple cancer types. Recurrently mutated regions tend to be cancer-type specific and overlap with cancer genes, suggesting that selection contributes to shaping the SV landscape. In total, we identified potentially pathogenic complex SVs in 42 tumors that affect cancer driver genes or result in unfavorable chromosomal alterations. Half of which were known drivers, e.g.MYCNamplifications due to ecDNA andEWSR1::FLI1fusions due to chromoplexy. Recurrent novel candidate complex events include chromoplexy inWT1in Wilms tumors, focal chromothripsis with 1p loss in hepatoblastomas and complexMDM2amplifications in rhabdomyosarcomas.ConclusionsComplex SVs are prevalent and pathogenic in pediatric solid tumors. They represent a type of genomic variation which currently remains unexplored. Moreover, carrying complex SVs seems to be associated with adverse clinical events. Our study highlights the potential for complex SVs to be incorporated in risk stratification or exploited for targeted treatments.
Hippocampal ripples linked to recognition memory judgments in children
Authors: Norman Yitzhak , Dorfmüller Georg , Taussig Delphine , Dorison Nathalie , Fohlen Martine , Chipaux Mathilde , Ferrand-Sorbets Sarah , Bulteau Christine , Harel Michal , Malach Rafael , Levy Mikael 
Published: September 2023

AbstractIntracranial studies have demonstrated significant roles for hippocampal ripples in human declarative memory. Yet, the developmental trajectory and contribution of ripples to memory processes in children remain unknown. We studied hippocampal ripple activity using intracranial recordings in 14 children (age: 6-14) undergoing epilepsy monitoring. After watching a pink panther cartoon twice, participants engaged in an old/new recognition test, determining whether events portrayed in short (4s) videoclips stemmed from the cartoon they had just viewed. Our results reveal a significant rise in ripple rate during successful recognition of familiar events. An anticipatory decline in ripple rate preceded recognition errors. Interestingly, when participants viewed the cartoon passively during the initial full-length screenings, the overall temporal pattern of ripple activation remained consistent across repetitions, and significantly distinct from explicit recognition. We conclude that hippocampal ripples in children play a key role in declarative memory, supporting the explicit identification of previously encountered events.