bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN
Authors: Shen John , Chowdhury Simon , Agarwal Neeraj , Karsh Lawrence I. , Oudard Stéphane , Gartrell Benjamin A. , Feyerabend Susan , Saad Fred , Pieczonka Christopher M. , Chi Kim N. , Brookman-May Sabine D. , Rooney Brendan , Bhaumik Amitabha , McCarthy Sharon A. , Bevans Katherine B. , Mundle Suneel D. , Small Eric J. , Smith Matthew R. , Graff Julie N. 
Published: November 2023

Abstract
Background
Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment.

Methods
Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures.

Results
Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40–0.80), 0.70 (0.54–0.91) and 0.74 (0.40–1.39) (TITAN) and 0.39 (0.19–0.78), 0.89 (0.69–1.16) and 0.81 (0.58–1.15) (SPARTAN) in patients aged <65, 65–79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups.

Conclusions
Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age.

Clinical trial registration
TITAN (NCT02489318); SPARTAN (NCT01946204).
FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment
Authors: Sun Xingzong , Qian Menghan , Li Hongliang , Wang Lei , Zhao Yunjie , Yin Min , Dai Lili , Bao Hongkun 
Published: November 2023

AbstractMultiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) that is characterized by myelin damage, followed by axonal and ultimately neuronal loss, which has been found to be associated with mitophagy. The etiology and pathology of MS remain elusive. However, the role of FK506 binding protein 5 (FKBP5, also called FKBP51), a newly identified gene associated with MS, in the progression of the disease has not been well defined. Here, we observed that the progress of myelin loss and regeneration in Fkbp5ko mice treated with demyelination for the same amount of time was significantly slower than that in wild-type mice, and that mitophagy plays an important regulatory role in this process. To investigate the mechanism, we discovered that the levels of FKBP5 protein were greatly enhanced in the CNS of cuprizone (CPZ) mice and the myelin-denuded environment stimulates significant activation of the PINK1/Parkin-mediated mitophagy, in which the important regulator, PPAR-γ, is critically regulated by FKBP5. This study reveals the role of FKBP5 in regulating a dynamic pathway of natural restorative regulation of mitophagy through PPAR-γ in pathological demyelinating settings, which may provide potential targets for the treatment of demyelinating diseases.
Constructing temporal networks with bursty activity patterns
Authors: Sheng Anzhi , Su Qi , Li Aming , Wang Long , Plotkin Joshua B. 
Published: November 2023

AbstractHuman social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions.
Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial
Authors: Lim Sun Min , Peters Solange , Ortega Granados Ana Laura , Pinto Gustavo dix Junqueira , Fuentes Christian Sebastián , Lo Russo Giuseppe , Schenker Michael , Ahn Jin Seok , Reck Martin , Szijgyarto Zsolt , Huseinovic Neda , Zografos Eleftherios , Buss Elena , Stjepanovic Neda , O’Donnell Sean , de Marinis Filippo 
Published: November 2023

AbstractPERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC.
The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization
Authors: Wang Wenshuai , Götte Benjamin , Guo Rong , Pyle Anna Marie 
Published: November 2023

AbstractRIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of which is ubiquitination of the RIG-I Caspase Recruitment Domains (CARDs) by E3 ligase Riplet. This is required for interaction between RIG-I and its downstream adapter protein MAVS, but the mechanism of action remains unclear. Here we show that Riplet is required for RIG-I signaling in the presence of both short and long dsRNAs, establishing that Riplet activation does not depend upon RIG-I filament formation on long dsRNAs. Likewise, quantitative Riplet-RIG-I affinity measurements establish that Riplet interacts with RIG-I regardless of whether the receptor is bound to RNA. To understand this, we solved high-resolution cryo-EM structures of RIG-I/RNA/Riplet complexes, revealing molecular interfaces that control Riplet-mediated activation and enabling the formulation of a unified model for the role of Riplet in signaling.
HSP47 levels determine the degree of body adiposity
Authors: Shin Jihoon , Toyoda Shinichiro , Okuno Yosuke , Hayashi Reiko , Nishitani Shigeki , Onodera Toshiharu , Sakamoto Haruyo , Ito Shinya , Kobayashi Sachiko , Nagao Hirofumi , Kita Shunbun , Otsuki Michio , Fukuhara Atsunori , Nagata Kazuhiro , Shimomura Iichiro 
Published: November 2023

AbstractAdiposity varies among individuals with the influence of diverse physiological, pathological, environmental, hormonal, and genetic factors, but a unified molecular basis remains elusive. Here, we identify HSP47, a collagen-specific chaperone, as a key determinant of body adiposity. HSP47 expression is abundant in adipose tissue; increased with feeding, overeating, and obesity; decreased with fasting, exercise, calorie restriction, bariatric surgery, and cachexia; and correlated with fat mass, BMI, waist, and hip circumferences. Insulin and glucocorticoids, respectively, up- and down-regulate HSP47 expression. In humans, the increase of HSP47 gene expression by its intron or synonymous variants is associated with higher body adiposity traits. In mice, the adipose-specific knockout or pharmacological inhibition of HSP47 leads to lower body adiposity compared to the control. Mechanistically, HSP47 promotes collagen dynamics in the folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPARγ protein from proteasomal degradation, partly related to MDM2. The study highlights the significance of HSP47 in determining the amount of body fat individually and under various circumstances.
Emergence of task-related spatiotemporal population dynamics in transplanted neurons
Authors: Ghuman Harman , Kim Kyungsoo , Barati Sapeeda , Ganguly Karunesh 
Published: November 2023

AbstractLoss of nervous system tissue after severe brain injury is a main determinant of poor functional recovery. Cell transplantation is a promising method to restore lost tissue and function, yet it remains unclear if transplanted neurons can demonstrate the population level dynamics important for movement control. Here we present a comprehensive approach for long-term single neuron monitoring and manipulation of transplanted embryonic cortical neurons after cortical injury in adult male mice performing a prehension task. The observed patterns of population activity in the transplanted network strongly resembled that of healthy networks. Specifically, the task-related spatiotemporal activity patterns of transplanted neurons could be represented by latent factors that evolve within a low dimensional manifold. We also demonstrate reliable modulation of the transplanted networks using minimally invasive epidural stimulation. Our approach may allow greater insight into how restoration of cell-type specific network dynamics in vivo can restore motor function.
Condensation of preformed charge density waves in kagome metals
Authors: Park Changwon , Son Young-Woo 
Published: November 2023

AbstractCharge density wave (CDW) is a spontaneous spatial modulation of charges in solids whose general microscopic descriptions are yet to be completed. Kagome metals of AV3Sb5 (A = K, Rb, Cs) provide a chance to realize CDW intertwined with dimensional effects as well as their special lattice. Here, based on a state-of-the-art molecular dynamics simulation, we propose that their phase transition to CDW is a condensation process of incoherently preformed charge orders. Owing to unavoidable degeneracy in stacking charge orders, phases of preformed orders on each layer are shown to fluctuate between a limited number of states with quite slower frequencies than typical phonon vibrations until reaching their freezing temperature. As the size of interfacial alkali atom increases, the fluctuations are shown to counterbalance the condensation of orderings, resulting in a maximized transition temperature for RbV3Sb5. Our results resolve controversial observations on their CDWs, highlighting a crucial role of their interlayer interactions.
Enhancing breadth and durability of humoral immune responses in non-human primates with an adjuvanted group 1 influenza hemagglutinin stem antigen
Authors: Swart Maarten , Kuipers Harmjan , Milder Fin , Jongeneelen Mandy , Ritschel Tina , Tolboom Jeroen , Muchene Leacky , van der Lubbe Joan , Izquierdo Gil Ana , Veldman Daniel , Huizingh Jeroen , Verspuij Johan , Schmit-Tillemans Sonja , Blokland Sven , de Man Martijn , Roozendaal Ramon , Fox Christopher B. , Schuitemaker Hanneke , Capelle Martinus , Langedijk Johannes P. M. , Zahn Roland , Brandenburg Boerries 
Published: November 2023

AbstractSeasonal influenza vaccines must be updated annually and suboptimally protect against strains mismatched to the selected vaccine strains. We previously developed a subunit vaccine antigen consisting of a stabilized trimeric influenza A group 1 hemagglutinin (H1) stem protein that elicits broadly neutralizing antibodies. Here, we further optimized the stability and manufacturability of the H1 stem antigen (H1 stem v2, also known as INFLUENZA G1 mHA) and characterized its formulation and potency with different adjuvants in vitro and in animal models. The recombinant H1 stem antigen (50 µg) was administered to influenza-naïve non-human primates either with aluminum hydroxide [Al(OH)3] + NaCl, AS01B, or SLA-LSQ formulations at week 0, 8 and 34. These SLA-LSQ formulations comprised of varying ratios of the synthetic TLR4 agonist ‘second generation synthetic lipid adjuvant’ (SLA) with liposomal QS-21 (LSQ). A vaccine formulation with aluminum hydroxide or SLA-LSQ (starting at a 10:25 µg ratio) induced HA-specific antibodies and breadth of neutralization against a panel of influenza A group 1 pseudoviruses, comparable with vaccine formulated with AS01B, four weeks after the second immunization. A formulation with SLA-LSQ in a 5:2 μg ratio contained larger fused or aggregated liposomes and induced significantly lower humoral responses. Broadly HA stem-binding antibodies were detectable for the entire period after the second vaccine dose up to week 34, after which they were boosted by a third vaccine dose. These findings inform about potential adjuvant formulations in clinical trials with an H1 stem-based vaccine candidate.
3D surgical instrument collection for computer vision and extended reality
Authors: Luijten Gijs , Gsaxner Christina , Li Jianning , Pepe Antonio , Ambigapathy Narmada , Kim Moon , Chen Xiaojun , Kleesiek Jens , Hölzle Frank , Puladi Behrus , Egger Jan 
Published: November 2023

AbstractThe availability of computational hardware and developments in (medical) machine learning (MML) increases medical mixed realities’ (MMR) clinical usability. Medical instruments have played a vital role in surgery for ages. To further accelerate the implementation of MML and MMR, three-dimensional (3D) datasets of instruments should be publicly available. The proposed data collection consists of 103, 3D-scanned medical instruments from the clinical routine, scanned with structured light scanners. The collection consists, for example, of instruments, like retractors, forceps, and clamps. The collection can be augmented by generating likewise models using 3D software, resulting in an inflated dataset for analysis. The collection can be used for general instrument detection and tracking in operating room settings, or a freeform marker-less instrument registration for tool tracking in augmented reality. Furthermore, for medical simulation or training scenarios in virtual reality and medical diminishing reality in mixed reality. We hope to ease research in the field of MMR and MML, but also to motivate the release of a wider variety of needed surgical instrument datasets.
Integrated flood risk assessment of properties and associated population at county scale for Nebraska, USA
Authors: Srivastava Shivendra , Roy Tirthankar 
Published: November 2023

AbstractRisk assessment of properties and associated population was conducted for the state of Nebraska, leveraging only open-source datasets. The flood risk framework consisted of interactions among drivers, i.e. hazard, exposure, vulnerability, and response, to assess the risks related to properties and associated populations. To quantify hazard on a county scale, we considered properties at risk of flooding based on a flood score (a higher score represents a greater chance of flooding). Exposure was quantified by considering population density at the county level. We quantified vulnerability under four categories: social, ecological, economic, and health. Response, a relatively newer component in flood risk assessment, was also quantified under three distinct categories: structural, non-structural, and emergency. Overall, we found that counties in eastern Nebraska (Sarpy, Dakota, Wayne, and Adams) have a higher risk of flooding consequences due to more exposure to vulnerable assets such as population and property. The assessment also observed that counties in eastern Nebraska are in the process of improving their flood control measures with dams, levees, and higher insurance coverage that can subdue the risks associated with flooding. The results from this study are anticipated to guide water managers and policymakers in making more effective and locally relevant policies and measures to mitigate flood risks and consequences.
Polaritonic and excitonic semiclassical time crystals based on TMDC strips in an external periodic potential
Authors: Martins Gabriel P. , Berman Oleg L. , Gumbs Godfrey 
Published: November 2023

AbstractWe investigated the dynamics of Bose–Einstein condensates (BECs) under an external periodic potential. We consider two such systems, the first being made of exciton–polaritons in a nanoribbon of transition metal dichalcogenides (TMDCs), such as MoSe$$_2$$

2

, embedded in a microcavity with a spatial curvature, which serves as the source of the external periodic potential. The second, made of bare excitons in a nanoribbon of twisted TMDC bilayer, which naturally creates a periodic Moiré potential that can be controlled by the twist angle. We proved that such systems behave as semiclassical time crystals (TCs). This was demonstrated by the fact that the calculated BEC spatial density profile shows a non-trivial long-range two-point correlator that oscillates in time. These BECs density profiles were calculated by solving the quantum Lindblad master equations for the density matrix within the mean-field approximation. We then go beyond the usual mean-field approach by adding a stochastic term to the master equation which corresponds to quantum corrections. We show that the TC phase is still present.
Reconfiguration and loss of peritubular capillaries in chronic kidney disease
Authors: Gaupp Charlotte , Schmid Benjamin , Tripal Philipp , Edwards Aurélie , Daniel Christoph , Zimmermann Stefan , Goppelt-Struebe Margarete , Willam Carsten , Rosen Seymour , Schley Gunnar 
Published: November 2023

AbstractFunctional and structural alterations of peritubular capillaries (PTCs) are a major determinant of chronic kidney disease (CKD). Using a software-based algorithm for semiautomatic segmentation and morphometric quantification, this study analyzes alterations of PTC shape associated with chronic tubulointerstitial injury in three mouse models and in human biopsies. In normal kidney tissue PTC shape was predominantly elongated, whereas the majority of PTCs associated with chronic tubulointerstitial injury had a rounder shape. This was reflected by significantly reduced PTC luminal area, perimeter and diameters as well as by significantly increased circularity and roundness. These morphological alterations were consistent in all mouse models and human kidney biopsies. The mean circularity of PTCs correlated significantly with categorized glomerular filtration rates and the degree of interstitial fibrosis and tubular atrophy (IFTA) and classified the presence of CKD or IFTA. 3D reconstruction of renal capillaries revealed not only a significant reduction, but more importantly a substantial simplification and reconfiguration of the renal microvasculature in mice with chronic tubulointerstitial injury. Computational modelling predicted that round PTCs can deliver oxygen more homogeneously to the surrounding tissue. Our findings indicate that alterations of PTC shape represent a common and uniform reaction to chronic tubulointerstitial injury independent of the underlying kidney disease.
m6A regulator-mediated methylation modification patterns and tumor microenvironment immune infiltration with prognostic analysis in esophageal cancer
Authors: Sheng Gaohong , Wang Tianqi , Gao Yuan , Wu Hua , Wu Jianhong 
Published: November 2023

AbstractEsophageal cancer is a highly malignant disease with poor prognosis. Despite recent advances in the study of esophageal cancer, there has been only limited improvement in the treatment and prognosis. N6-methyladenosine (m6A), a type of RNA modification, has been extensively investigated and is involved in many biological behaviors, including tumorigenesis and progression. Thus, more research on m6A modification may increase our understanding of esophageal cancer pathogenesis and provide potential targets. In our study, we integrated the public data of esophageal cancer from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO) databases. Unsupervised clustering analysis was used to classify patients into different groups. Gene set variation analysis (GSVA) was performed in a nonparametric and unsupervised mode. We evaluated immune cell infiltration by single sample gene set enrichment analysis (ssGSEA). Differentially expressed genes (DEGs) among m6A clusters were identified using Empirical Bayesian approach. Both multivariate and univariate Cox regression models were used for prognostic analysis. We provided an overview of gene variation and expression of 23 m6A regulators in esophageal cancer, as well as their effects on survival. Based on the overall expression level of m6A regulators, patients were classified into three m6A clusters (A-C) with different immune cell infiltration abundance, gene expression signatures and prognosis. Among m6A clusters, we identified 206 DEGs, according to which patients were classified into 4 gene clusters (A-D). Quantitative m6A score was calculated for each patient based on those DEGs with significant impact on survival. The infiltration of all types of immune cells except type 2 T helper (Th2) cells were negatively correlated with m6A score. M6Acluster C exhibited the lowest m6A score, the most abundant immune cell infiltration, and the worst prognosis, suggesting an immune excluded phenotype. Consistently, gene cluster D with the lowest m6A score showed the worst prognosis. In short, patients with esophageal cancer showed different m6A modification patterns. Quantitative scoring indicated that patients with the lowest m6A score exhibited the most abundant immune cell infiltration and the poorest prognosis. This m6A scoring system is promising to assess m6A modification pattern, characterize immune infiltration and guide personalized treatment and prognostic prediction.