bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Force Fitness: Making Holistic, Integrated Whole-Person Research a DoD Priority
Authors: Deuster Patricia A , Meyer Vanessa M , Langevin Helene M 
Published: September 2023

ABSTRACT
Total Force Fitness (TFF) was conceived as a holistic framework for building and sustaining Human Performance Optimization for Warfighters and their families. As such, TFF research must also be holistic in nature. During the research breakout, group barriers and challenges to TFF research were discussed, and critical research focus areas were prioritized. The top approaches discussed were (1) using big data to identify best practices and health trajectories; (2) applying community-based participatory research principles to military units; (3) focusing on “Whole-Person,” integrative research (physical, behavioral, spiritual, and biological) across the Department of Defense; and, finally, (4) prioritizing key opportunities to advance TFF across the active duty and Reserve/Guard enterprises and their families. The research group noted that coordinated action would be needed to move the prioritized agenda forward. Finally, translating research into action is essential because TFF is a way of honoring our service members as whole persons with careers, goals, and families.
Towards a History of the Eccentric Artist: Beethoven’s Bad Manners and the Lure of the Anecdote
Authors: Fine Abigail 
Published: September 2023

ABSTRACT
Since the late nineteenth century, Beethoven’s bad manners have been framed as a political act of resistance against the stilted affect of the nobility. Yet this posthumous view does not fully account for how Beethoven’s contemporaries understood his (mis)behaviour. This article situates reactions to Beethoven’s bad manners that originated during his lifetime, alongside anecdotes published shortly after his death, to show how the eccentric artist persona interfaced with a history of etiquette. The very act of noticing behavioural minutiae took part in a celebrity culture poised on the cusp of novelty and conformity, entertainment and moral instruction. In a period dominated by conduct books, Beethoven’s friends sought to reconcile his gaffes with sensibility and (mannered) naturalness, reframing him as an ideal bourgeois subject. The case of Beethoven not only sheds light on the formation of the eccentric artist, but on the lure of the anecdote as an imaginative form of re-enactment.
The linear response of stellar systems does not diverge at marginal stability
Authors: Hamilton Chris , Heinemann Tobias 
Published: September 2023

ABSTRACT
The linear response of a stellar system’s gravitational potential to a perturbing mass comprises two distinct contributions. Most famously, the system will respond by forming a polarization ‘wake’ around the perturber. At the same time, the perturber may also excite one or more ‘Landau modes’, i.e. coherent oscillations of the entire stellar system which are either stable or unstable depending on the system parameters. The amplitude of the first (wake) contribution is known to diverge as a system approaches marginal stability. In this paper, we consider the linear response of a homogeneous stellar system to a point mass moving on a straight line orbit. We prove analytically that the divergence of the wake response is in fact cancelled by a corresponding divergence in the Landau mode response, rendering the total response finite. We demonstrate this cancellation explicitly for a box of stars with Maxwellian velocity distribution. Our results imply that polarization wakes may be much less efficient drivers of secular evolution than previously thought. More generally, any prior calculation that accounted for wakes but ignored modes – such as those based on the Balescu-Lenard equation – may need to be revised.
A transient ultraviolet outflow in the short-period X-ray binary UW CrB
Authors: Fijma S , Castro Segura N , Degenaar N , Knigge C , Higginbottom N , Hernández Santisteban J V , Maccarone T J 
Published: September 2023

ABSTRACT
Accreting low-mass X-ray binaries (LMXBs) are capable of launching powerful outflows such as accretion disc winds. In disc winds, vast amounts of material can be carried away, potentially greatly impacting the binary and its environment. Previous studies have uncovered signatures of disc winds in the X-ray, optical, near-infrared, and recently even the ultraviolet (UV) band, predominantly in LMXBs with large discs (Porb ≥ 20 h). Here, we present the discovery of transient UV outflow features in UW CrB, a high-inclination (i ≥ 77°) neutron star LMXB (NS-LMXB) with an orbital period of only Porb ≈ 111 min. We present P-Cygni profiles identified for Si iv 1400 Å and tentatively for N v 1240 Å in one 15 min exposure, which is the only exposure covering orbital phase ϕ ≈ 0.7–0.8, with a velocity of ≈1500 km s−1. We show that due to the presence of blackbody emission from the neutron star surface and/or boundary layer, a thermal disc wind can be driven despite the short Porb, but explore alternative scenarios as well. The discovery that thermal disc winds may occur in NS-LMXBs with Porb as small as ≈111 min, and can potentially be transient on time-scales as short as ≈15 min, warrants further observational and theoretical work.
Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity
Authors: Syed Aleem , Filandr Frantisek , Patterson-Fortin Jeffrey , Bacolla Albino , Ravindranathan Ramya , Zhou Jia , McDonald Drew T , Albuhluli Mohammed E , Verway-Cohen Amy , Newman Joseph A , Tsai Miaw-Sheue , Jones Darin E , Schriemer David C , D’Andrea Alan D , Tainer John A 
Published: September 2023

Abstract
Polymerase theta (Polθ) acts in DNA replication and repair, and its inhibition is synthetic lethal in BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB) is a first-in-class inhibitor of the Polθ ATPase activity, and it is currently being tested in clinical trials as an anti-cancer drug. Here, we investigated the molecular mechanism of NVB-mediated Polθ inhibition. Using hydrogen deuterium exchange-mass spectrometry (HX-MS), biophysical, biochemical, computational and cellular assays, we found NVB is a non-competitive inhibitor of ATP hydrolysis. NVB sugar group deletion resulted in decreased potency and reduced HX-MS interactions, supporting a specific NVB binding orientation. Collective results revealed that NVB binds to an allosteric site to block DNA binding, both in vitro and in cells. Comparisons of The Cancer Genome Atlas (TCGA) tumors and matched controls implied that POLQ upregulation in tumors stems from its role in replication stress responses to increased cell proliferation: this can now be tested in fifteen tumor types by NVB blocking ssDNA-stimulation of ATPase activity, required for Polθ function at replication forks and DNA damage sites. Structural and functional insights provided in this study suggest a path for developing NVB derivatives with improved potency for Polθ inhibition by targeting ssDNA binding with entropically constrained small molecules.
Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group
Authors: Karschnia Philipp , Dietrich Jorg , Bruno Francesco , Dono Antonio , Juenger Stephanie T , Teske Nico , Young Jacob S , Sciortino Tommaso , Häni Levin , van den Bent Martin , Weller Michael , Vogelbaum Michael A , Morshed Ramin A , Haddad Alexander F , Molinaro Annette M , Tandon Nitin , Beck Juergen , Schnell Oliver , Bello Lorenzo , Hervey-Jumper Shawn , Thon Niklas , Grau Stefan J , Esquenazi Yoshua , Rudà Roberta , Chang Susan M , Berger Mitchel S , Cahill Daniel P , Tonn Joerg-Christian 
Published: September 2023

Abstract

Background
Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a ‘low-grade appearance’ on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

Methods
The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement.

Results
Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables.

Conclusions
The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.
Longitudinal analysis of serum-derived extracellular vesicle RNA to monitor dacomitinib treatment response in EGFR-amplified recurrent glioblastoma patients
Authors: Yekula Anudeep , Hsia Tiffaney , Kitchen Robert R , Chakrabortty Sudipto K , Yu Wei , Batool Syeda M , Lewis Brian , Szeglowski Antoni J , Weissleder Ralph , Lee Hakho , Chi Andrew S , Batchelor Tracy , Carter Bob S , Breakefield Xandra O , Skog Johan , Balaj Leonora 
Published: September 2023

Abstract

Background
Glioblastoma (GBM) is a highly aggressive and invasive brain tumor associated with high patient mortality. A large fraction of GBM tumors have been identified as epidermal growth factor receptor (EGFR) amplified and ~50% also are EGFRvIII mutant positive. In a previously reported multicenter phase II study, we have described the response of recurrent GBM (rGBM) patients to dacomitinib, an EGFR tyrosine kinase inhibitor (TKI). As a continuation of that report, we leverage the tumor cargo-encapsulating extracellular vesicles (EVs) and explore their genetic composition as carriers of tumor biomarker.

Methods
Serum samples were longitudinally collected from EGFR-amplified rGBM patients who clinically benefitted from dacomitinib therapy (responders) and those who did not (nonresponders), as well as from a healthy cohort of individuals. The serum EV transcriptome was evaluated to map the RNA biotype distribution and distinguish GBM disease.

Results
Using long RNA sequencing, we show enriched detection of over 10 000 coding RNAs from serum EVs. The EV transcriptome yielded a unique signature that facilitates differentiation of GBM patients from healthy donors. Further analysis revealed genetic enrichment that enables stratification of responders from nonresponders prior to dacomitinib treatment as well as following administration.

Conclusion
This study demonstrates that genetic composition analysis of serum EVs may aid in therapeutic stratification to identify patients with dacomitinib-responsive GBM.
Are we providing best-available care to newly diagnosed glioblastoma patients? Systematic review of phase III trials in newly diagnosed glioblastoma 2005–2022
Authors: Oster Christoph , Schmidt Teresa , Agkatsev Sarina , Lazaridis Lazaros , Kleinschnitz Christoph , Sure Ulrich , Scheffler Björn , Kebir Sied , Glas Martin 
Published: September 2023

Abstract

Background
Glioblastoma is the most aggressive primary brain cancer with a poor prognosis. Despite numerous studies in the past 17 years, effective treatment options for glioblastoma remain limited. In this study, we aimed to identify and compare phase III clinical trials for glioblastoma in terms of efficacy and baseline characteristics.

Methods
A systematic literature search was conducted using PubMed and ClinicalTrials.gov to identify phase III clinical trials for glioblastoma in adult patients. The target population included adult patients aged 18 years and above (younger cohort) and patients ≥60 years of age (elderly cohort). The search results were screened based on predefined inclusion criteria, and the included trials were analyzed for their study design, baseline characteristics, and survival results.

Results
Eleven trials met the inclusion criteria in the younger cohort. Of these, three reported a statistically significant improvement in overall survival (OS), including the EORTC/NCIC study (NCT00006353), EF-14 (NCT00916409), and CeTeG (NCT01149109). Of the 11 trials, eight were open-label randomized trials, including all of the positive ones, while three negative trials employed treatment blinding and a placebo control. The baseline characteristics of the trials [such as extent of resection, age, gender, and O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status] did not significantly differ between positive and negative trials. Isocitrate dehydrogenase (IDH) mutation status was analyzed in only two trials, with a small percentage of IDH-mutated tumors in each. Additionally, three more trials in the elderly cohort showed a statistically significant improvement of OS, the NOA-08 trial, the ISRCTN81470623-trial by Malmström et al. and NCT00482677-trial by Perry et al. Their baseline characteristics and implications are also analyzed.

Conclusion
This analysis of phase III clinical trials for glioblastoma conducted since 2005 showed that the majority of trials did not result in a significant improvement in OS. Among the trials included in this analysis, only the EORTC/NCIC, EF-14, and CeTeG studies demonstrated a positive OS outcome in the younger cohort.
Prognostic impact of malnutrition in patients with coronary artery disease: a systematic review and meta-analysis
Authors: He Fengling , Huang Haoxiang , Xu Wenlong , Cui Kai , Ruan Yifei , Guo Yuetong , Wang Junfen , Bin Jianping , Wang Yuegang , Chen Yanmei 
Published: September 2023

AbstractContextConflicting predictions of malnutrition for the long-term prognosis of coronary artery disease (CAD) exist.ObjectiveThis study aimed to investigate the relationship between malnutrition and long-term prognosis of patients with CAD.Data SourcesFour databases were searched for articles from February 11, 1936, to September 10, 2022.Data ExtractionCohort studies adjusting for multiple cardiovascular risk factors with data on CAD and malnutrition were included. Malnutrition was measured and defined by different nutritional evaluation tools. The hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality and major adverse cardiovascular events (MACEs) were synthesized. Subgroup analyses were performed based on study design, assessment tools, ethnicity/race, follow-up, sample size, and types of CAD. Meta-regression was used to compare whether the effect sizes of the 2 subgroups were statistically significant.Data AnalysisA total of 30 cohort studies were included, totaling 81 361 participants with CAD. Nutritional evaluation tools, including the Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), Nutritional Risk Screening 2002, Mini-Nutritional Assessment, and Prognostic Nutritional Index, were used. Malnutrition increased all-cause mortality (HR = 1.72; 95% CI: 1.53, 1.93) and MACEs (HR = 1.47; 95% CI: 1.35, 1.60) in patients with CAD. Subgroup analysis revealed the results were consistent across study design, ethnicity/race, follow-up, sample size, and types of CAD. Subgroup analyses and meta-regression revealed that malnutrition was associated with a higher risk of all-cause mortality (HR = 2.26; 95% CI: 1.91, 2.68) and MACEs (HR = 2.28; 95% CI: 1.69, 3.08) in patients with stable CAD than those with other types of CAD. Meta-regression revealed that the GNRI (HR = 2.20; 95% CI: 1.65, 2.93) was more effective than CONUT (HR = 1.47; 95% CI: 1.21, 1.78) in predicting all-cause mortality.ConclusionMalnutrition independently increased all-cause mortality by 72% and MACEs by 47% in patients with CAD, especially with stable CAD. The GNRI is a more effective nutritional evaluation tool than CONUT in predicting all-cause mortality.
Microorganisms Detected in Intussusception Cases and Controls in Children &lt;3 Years in South Africa From 2013 to 2017
Authors: Page Nicola Anne , Netshikweta Rembuluwani , Tate Jacqueline E , Madhi Shabir A , Parashar Umesh D , Groome Michelle J ,   the South African Intussusception Surveillance Group, Arnold Marion , Chitnis Milind , Cox Sharon , de Vos Corné , Kirsten Mari , le Grange Susanna M , Loveland Jerome , Machaea Sello , Maharaj Ashwini , Withers Aletha 
Published: September 2023

Abstract
A matched case-control evaluated infectious etiologies in children &lt;3 years in post-rotavirus vaccine intussusception surveillance. Adenovirus and adenovirus types C, A, and B were detected more frequently in cases versus controls at statistically significant values. Wild-type rotavirus, rotavirus vaccine strains, and human herpesvirus were not associated with intussusception.
Oryza glumaepatula: A wild relative to improve drought tolerance in cultivated rice
Authors: Thathapalli Prakash Parthiban , Chebotarov Dmytro , Zhang Jianwei , Kudrna David A , Torres Rolando O , Natividad Mignon A , Quintana Marinell R , Song Jiaming , Maldonado Carlos E , Hechanova Sherry Lou , Jena Kshirod , Wing Rod A , Henry Amelia 
Published: September 2023

Abstract
Developing drought-resistant rice (Oryza sativa, L.) is essential for improving field productivity, especially in rain-fed areas affected by climate change. Wild relatives of rice are potential sources for drought-resistant traits. Therefore, we compared root growth and drought response among 22 wild Oryza species, from which Oryza glumaepatula was selected as a promising source for further exploration. A geographically diverse panel of 69 O. glumaepatula accessions was then screened for drought stress-related traits, and 6 of these accessions showed lower shoot dry weight (SDW) reduction, greater percentage of deep roots, and lower stomatal density (STO) under drought than the drought tolerant O. sativa variety, Sahbhagi dhan. Based on whole-genome resequencing of all 69 O. glumaepatula accessions and variant calling to a high-quality O. glumaepatula reference genome, we detected multiple genomic loci colocating for SDW, root dry weight at 30 to 45 cm depth, and STO in consecutive drought trials. Geo-referencing indicated that the potential drought donors originated in flood-prone locations, corroborating previous hypotheses about the coexistence of flood and drought tolerance within individual Oryza genomes. These findings present potential donor accessions, traits, and genomic loci from an AA genome wild relative of rice that, together with the recently developed reference genome, may be useful for further introgression of drought tolerance into the O. sativa backgrounds.
Abstract 1 Clinical and Imaging Outcomes After Allogenic Umbilical Cord Blood Transfusions in a Young Adult with Cerebral Palsy
Authors: Tseng Sung Hui , Lu Long-Sheng , Kuo Chen-Yuan , Lin Ching Po , Yeh Tu-Hsueh 
Published: September 2023

Abstract

Introduction
Umbilical cord blood transplant is an emerging promising therapy for cerebral palsy. Here we report a case of a 23-year-old spastic quadriplegic young adult whose motor and cognitive function improved after allogenic umbilical cord blood transfusion.

Methods
The patient received three times of cord blood transfusion intravenously (2022/2/15, 2022/05/16, 2022/8/15). Each cord blood was 4/6 HLA-matched and contained 10 × 107 total nucleated cells (TNC)/kg.

Results
The young man was born preterm. Due to motor developmental delay, he began rehabilitation when 1-year-old. His best mobility function was GMFCS III. At the age of 18, there was a rapid decline of his mobility. EEG showed seizure like waves and TRODAT brain scan on 2018/9/28 revealed symmetric mild striatal dopaminergic neuron loss. He was totally ADL dependent and mobility and communication severely restricted due to strong spasticity and rigidity. 3 days after 1st cord blood transfusion, he walked 500 steps (1 km/h) on LOKOMAT with 100% guidance force and 50% body weight supported. In the 16th session (when he also completed the 3rd cord blood transfusion), he walked1000 steps (1.5 km/h) on LOKOMAT with 90% guidance force and 50% body weight supported. Afterward, he regained sufficient motor function to maintain daily training with traditional physiotherapy. There was no adverse event during all the transplant procedures. Brain images taken before and after cord blood transfusion were compared with a brain-age predicting model to obtain differences in predicted and chronological age in 3 sets of brain images. The result showed reduced differences between predicted and chronological brain age (Figure 1). His mother reported that he became more alert and more responsive during interaction.

Discussio
This case highlights the therapeutic effect of allogenic umbilical cord blood transfusion to benefit adult CP manifest deterioration in physical activity and cognitive function. The specific mechanisms involved in this process are not yet fully understood. Therefore, any use of stem cell transplantation for the treatment of cerebral palsy should be done under the guidance of good clinical practice to accumulate robust real-world data, and more research is needed to fully understand its mechanisms of action.