bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gens sans argent: A New Holograph Manuscript by Thomas Hoccleve
Authors: Sobecki Sebastian 
Published: October 2024

Abstract
This article introduces an unknown personal holograph manuscript by Thomas Hoccleve: Cambridge, Trinity College, MS O. 7. 43. The new manuscript, only recently digitized, has never been associated with Hoccleve; in fact, it has lived under the radar of literary scholarship for the last six hundred years. The manuscript is here described, then it is demonstrated palaeographically that it is written in Hoccleve’s hand; the contents are discussed with some of the implications of this discovery. In conclusion, it is suggested that the manuscripts bequeathed in 1738 by Roger Gale to Trinity College could preserve four others that the poet may have owned, raising the probability that the Gale bequest represents a portion of Hoccleve’s private library.
PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators
Authors: Wang Yuexi , Chembazhi Ullas Valiya , Yee Danielle , Chen Sijie , Ji Jie , Wang Yujie , Nguyen Ka Lam , Lin PoChing , Ratti Antonia , Hess Rex A , Qiao Huanyu , Ko CheMyong , Yang Jing , Kalsotra Auinash , Mei Wenyan 
Published: October 2024

Abstract
Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of the Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that the RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics are controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.
oriTDB: a database of the origin-of-transfer regions of bacterial mobile genetic elements
Authors: Liu Guitian , Li Xiaobin , Guan Jiahao , Tai Cui , Weng Yuqing , Chen Xiaohua , Ou Hong- Yu 
Published: October 2024

Abstract
Conjugation and mobilization are two important pathways of horizontal transfer of bacterial mobile genetic elements (MGEs). The origin-of-transfer (oriT) region is crucial for this process, serving as a recognition site for relaxase and containing the DNA nicking site (nic site), which initiates the conjugation or mobilization. Here, we present a database of the origin-of-transfer regions of bacterial MGEs, oriTDB (https://bioinfo-mml.sjtu.edu.cn/oriTDB2/). Incorporating data from text mining and genome analysis, oriTDB comprises 122 experimentally validated and 22 927 predicted oriTs within bacterial plasmids, Integrative and Conjugative Elements, and Integrative and Mobilizable Elements. Additionally, oriTDB includes details about associated relaxases, auxiliary proteins, type IV coupling proteins, and a gene cluster encoding the type IV secretion system. The database also provides predicted secondary structures of oriT sequences, dissects oriT regions into pairs of inverted repeats, nic sites, and their flanking conserved sequences, and offers an interactive visual representation. Furthermore, oriTDB includes an enhanced oriT prediction pipeline, oriTfinder2, which integrates a functional annotation module for cargo genes in bacterial MGEs. This resource is intended to support research on bacterial conjugative or mobilizable elements and promote an understanding of their cargo gene functions.
PhageDive: the comprehensive strain database of prokaryotic viral diversity
Authors: Rolland Clara , Wittmann Johannes , Reimer Lorenz C , Sardà Carbasse Joaquim , Schober Isabel , Dudek Christian-Alexander , Ebeling Christian , Koblitz Julia , Bunk Boyke , Overmann Jörg 
Published: October 2024

Abstract
Prokaryotic viruses represent the most diverse and abundant biological entities on Earth. So far, data on bacteriophages are not standardized, not readily available for comparative analyses and cannot be linked to the rapidly growing (meta)genomic data. We developed PhageDive (https://phagedive.dsmz.de), a comprehensive database for prokaryotic viruses gathering all existing data dispersed across multiple sources, like scientific publications, specialized databases or internal files of culture collections. PhageDive allows to link own research data to the existing information through an easy and central access, providing fields for various experimental data (host range, genomic data, etc.) and available metadata (e.g. geographical origin, isolation source). An important feature is the link between experimental data, the culture collection number and the repository of the corresponding physical bioresource. To date, PhageDive covers 1167 phages from three different world-renowned public collections (DSMZ, Félix d’Hérelle Reference Center for Bacterial Viruses and NCTC) and features an advanced search function using all data fields from the sections like taxonomy or morphology by controlled vocabulary and ontologies. PhageDive is fully interoperable with other resources including NCBI, the Viral Host Range database (VHRdb) of Institute Pasteur or the BacDive and MediaDive databases of DSMZ.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017–2021
Authors: Price Mackenzie , Ballard Christine , Benedetti Julia , Neff Corey , Cioffi Gino , Waite Kristin A , Kruchko Carol , Barnholtz-Sloan Jill S , Ostrom Quinn T 
Published: October 2024

Abstract
The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.
EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma
Authors: Koh Lynnette Wei Hsien , Pang Qing You , Novera Wisna , Lim See Wee , Chong Yuk Kien , Liu Jinyue , Ang Samantha Ya Lyn , Loh Ron Weng Yee , Shao Huilin , Ching Jianhong , Wang Yulan , Yip Stephen , Tan Patrick , Li Shang , Low David Chyi Yeu , Phelan Anne , Rosser Gabriel , Tan Nguan Soon , Tang Carol , Ang Beng Ti 
Published: October 2024

Abstract

Background
Enhancer of zeste homolog 2 (EZH2), well known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied noncanonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratification remain relatively unexplored. Current enzymatic EZH2 inhibitors (EZH2inh) targeting its canonical su(var)3–9, enhancer-of-zeste and trithorax domain show limited efficacy and lack durable response, suggesting that underlying differences in the noncanonical pathway may yield new knowledge. Here, we unveiled dual roles of the EZH2 CXC domain in therapeutically distinct, reactive oxygen species (ROS)-stratified tumors.

Methods
We analyzed differentially expressed genes between ROS classes by examining cis-regulatory elements as well as clustering of activities and pathways to identify EZH2 as the key mediator in ROS-stratified cohorts. Pull-down assays and CRISPR knockout of EZH2 domains were used to dissect the distinct functions of EZH2 in ROS-stratified GBM cells. The efficacy of NF-κB-inducing kinase inhibitor (NIKinh) and standard-of-care temozolomide was evaluated using orthotopic patient-derived GBM xenografts.

Results
In ROS(+) tumors, CXC-mediated co-interaction with RelB drives constitutive activation of noncanonical NF-κB2 signaling, sustaining the ROS(+) chemoresistant phenotype. In contrast, in ROS(−) subtypes, Polycomb Repressive Complex 2 methyltransferase activity represses canonical NF-κB. Addressing the lack of EZH2inh targeting its nonmethyltransferase roles, we utilized a brain-penetrant NIKinh that disrupts EZH2-RelB binding, consequently prolonging survival in orthotopic ROS(+)-implanted mice.

Conclusions
Our findings highlight the functional dichotomy of the EZH2 CXC domain in governing ROS-stratified therapeutic resistance, thereby advocating for the development of therapeutic approaches targeting its noncanonical activities and underscoring the significance of patient stratification methodologies.
Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate
Authors: Moini Katayoun , Seery Tara , Nangia Chaitali , MacDiarmid Jennifer , Brahmbhatt Himanshu , Spilman Patricia , Sender Lennie , Soon-Shiong Patrick 
Published: October 2024

Abstract
Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC). Here, we report the compassionate use treatment of this combination in a patient with recurrent, metastatic pancreatic cancer (mPC) after 3 lines of therapy. Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months. The patient’s disease became stable on this regimen, and a transient complete response was observed by ~14 months of therapy. Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient’s continued survival at the time this report was written. The patient’s extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity required for tumor response and extended survival.
Assessing the Adequacy of Morphological Models Using Posterior Predictive Simulations
Authors: Mulvey Laura P A , May Michael R , Brown Jeremy M , Höhna Sebastian , Wright April M , Warnock Rachel C M 
Published: October 2024

Abstract
Reconstructing the evolutionary history of different groups of organisms provides insight into how life originated and diversified on Earth. Phylogenetic trees are commonly used to estimate this evolutionary history. Within Bayesian phylogenetics a major step in estimating a tree is in choosing an appropriate model of character evolution. While the most common character data used is molecular sequence data, morphological data remains a vital source of information. The use of morphological characters allows for the incorporation fossil taxa, and despite advances in molecular sequencing, continues to play a significant role in neontology. Moreover, it is the main data source that allows us to unite extinct and extant taxa directly under the same generating process. We therefore require suitable models of morphological character evolution, the most common being the Mk Lewis model. While it is frequently used in both palaeobiology and neontology, it is not known whether the simple Mk substitution model, or any extensions to it, provide a sufficiently good description of the process of morphological evolution. In this study we investigate the impact of different morphological models on empirical tetrapod datasets. Specifically, we compare unpartitioned Mk models with those where characters are partitioned by the number of observed states, both with and without allowing for rate variation across sites and accounting for ascertainment bias. We show that the choice of substitution model has an impact on both topology and branch lengths, highlighting the importance of model choice. Through simulations, we validate the use of the model adequacy approach, posterior predictive simulations, for choosing an appropriate model. Additionally, we compare the performance of model adequacy with Bayesian model selection. We demonstrate how model selection approaches based on marginal likelihoods are not appropriate for choosing between models with partition schemes that vary in character state space (i.e., that vary in Q-matrix state size). Using posterior predictive simulations, we found that current variations of the Mk model are often performing adequately in capturing the evolutionary dynamics that generated our data. We do not find any preference for a particular model extension across multiple datasets, indicating that there is no “one size fits all” when it comes to morphological data and that careful consideration should be given to choosing models of discrete character evolution. By using suitable models of character evolution, we can increase our confidence in our phylogenetic estimates, which should in turn allow us to gain more accurate insights into the evolutionary history of both extinct and extant taxa.
Epidemiology, Process of Care, and Associated Outcomes of Pediatric Out-of-Hospital Cardiac Arrest in China: Results From a Prospective, Multicenter, Population-Based Registry
Authors: Zhao Xiangkai , Zheng Wen , Ma Yu , Hou Yaping , Zhu Yimin , Zheng Jiaqi , Wang Quan , Pan Chang , Zhang Jianbo , Wang Chunyi , Bian Yuan , Liu Rugang , Cheng Kai , Ma Jingjing , Ong Marcus Eng Hock , Xu Feng , Chen Yuguo ,   on behalf of the Baseline Investigation of Out-of-Hospital Cardiac Arrest (BASIC-OHCA) Coordinators and Investigators
Published: October 2024

OBJECTIVES:
To comprehensively describe the incidence, process of care, outcomes, and variation among different age groups of pediatric out-of-hospital cardiac arrest (OHCA) in China.

DESIGN:
The Baseline Investigation of Out-of-Hospital Cardiac Arrest (BASIC-OHCA) is a prospective, multicenter, population-based registry of emergency medical services (EMS)-assessed OHCA in China.

SETTING:
A total of 25 monitoring sites of all seven geographical regions were included, covering a pediatric population (age ≤ 19) of around 22.3 million in China.

PATIENTS:
Pediatric patients enrolled in BASIC-OHCA from August 2019 to December 2020 were included.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
A total of 1493 pediatric patients with EMS-assessed OHCA were enrolled, and resuscitation was attempted in 651 cases (43.6%). The crude incidence of EMS-assessed and EMS-treated OHCA was 5.5 (95% CI, 5.2–5.9) and 2.4 (95% CI, 2.2–2.6) per 100,000 pediatric population. Among 651 EMS-treated OHCA cases, 434 patients (66.7%) were male, and 353 (54.2%) had nonmedical causes (trauma, asphyxia, and drowning being the most common). There were 396 patients (60.8%) who collapsed at home, and the proportion of cases that occurred in public places such as streets and schools increased with age. There were 26 patients (4.0%) who had an initial shockable rhythm. For 626 non-EMS-witnessed patients, 152 patients (24.3%) received bystander cardiopulmonary resuscitation (CPR), 68 (10.9%) received dispatcher-assisted CPR, and 3 (0.5%) had automated external defibrillator applied. The survival to discharge or 30 days was 3.5% (23/651), and the favorable neurologic prognosis was 3.1% (20/651), with no differences among age groups.

CONCLUSIONS:
This study provides the first national exploration of pediatric OHCA in China. The high proportion of nonmedical causes underscores the importance of preventing accidents in children. Gaps in the chain of survival and patient outcomes provide a focus for improving the treatment of pediatric OHCA in China and other developing countries.
Geometric mechanics of kiri-origami-based bifurcated mechanical metamaterials
Authors: Li Yanbin , Zhou Caizhi , Yin Jie 
Published: October 2024

We explore a new design strategy of leveraging kinematic bifurcation in creating origami/kirigami-based three-dimensional (3D) hierarchical, reconfigurable, mechanical metamaterials with tunable mechanical responses. We start from constructing three basic, thick, panel-based structural units composed of 4, 6 and 8 rigidly rotatable cubes in close-looped connections. They are modelled, respectively, as 4R, 6R and 8R (R stands for revolute joint) spatial looped kinematic mechanisms, and are used to create a library of reconfigurable hierarchical building blocks that exhibit kinematic bifurcations. We analytically investigate their reconfiguration kinematics and predict the occurrence and locations of kinematic bifurcations through a trial-correction modelling method. These building blocks are tessellated in 3D to create various 3D bifurcated hierarchical mechanical metamaterials that preserve the kinematic bifurcations in their building blocks to reconfigure into different 3D architectures. By combining the kinematics and considering the elastic torsional energy stored in the folds, we develop the geometric mechanics to predict their tunable anisotropic Poisson’s ratios and stiffnesses. We find that kinematic bifurcation can significantly effect mechanical responses, including changing the sign of Poisson’s ratios from negative to positive beyond bifurcation, tuning the anisotropy, and overcoming the polarity of structural stiffness and enhancing the number of deformation paths with more reconfigured shapes.
This article is part of the theme issue ‘Origami/Kirigami-inspired structures: from fundamentals to applications’.
Blunted anterior midcingulate response to reward in opioid users is normalized by prefrontal transcranial magnetic stimulation
Authors: Biernacki Kathryn , Goldstein Rita Z. , Güth Malte R. , Alia-Klein Nelly , Ray Suchismita , Baker Travis E. 
Published: October 2024

AbstractIntroductionAbnormalities in goal-directed behavior, mediated by mesocorticolimbic reward function and structure, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU).Material and MethodIn a sham-controlled randomized study design, we measured whether robot-assisted 10Hz transcranial magnetic stimulation (TMS) applied to the prefrontal cortex was able to modulate anterior midcingulate cortex (MCC) electrophysiological response to rewards, in OU and matched healthy controls.ResultsWe show that OU exhibit a blunted anterior MCC reward response, compared to healthy controls (t(39) = 2.62, p = 0.01, d = 0.84), and that this is normalized following 10-Hz excitatory TMS (t(36)= .82, p = 0.42, d = 0.17).ConclusionsExcitatory TMS modulated the putative reward function of the MCC in OU. Further work with increased sample sizes and TMS sessions is required to determine whether restoring MCC reward function increases reward-directed behaviors, which may enhance treatment success through the maintenance of treatment goals.
PILocarpine 1.25% Efficacy for management of Uncorrected Presbyopia (PILE-UP Study)
Authors: Saxena Rohit , Gupta Vinay , Velpandian T , Nidhi Tanya , Thakur Himani , Titiyal Jeewan S , Sharma Namrata 
Published: October 2024

AbstractPurposeThis study aimed to evaluate the efficacy and safety of pilocarpine 1.25% eye drops for improving near vision acuity in presbyopic individuals.DesignNon-randomized prospective interventional trialMethodsThis single-arm prospective interventional trial includesfifty presbyopic individuals aged between 40 to 55, administrated pilocarpine 1.25% eye-drops daily once (9 am, Hour 0) for one month. Visual parameters, including distance corrected near visual acuity (DCNVA), near add power, amplitude of accommodation (AoA), and depth of focus (DoF) along with ocular biometric parameters were assessed at baseline and after one month at hour 3 (12 noon) and hour 6 (3 p.m.). Adverse effects were monitored.ResultsAfter one month of pilocarpine treatment, a significant improvement was observed in DCNVA (0.64±0.2 to 0.26±0.11,P:<0.001) along with a decrease in near add power (1.43±0.43 D to 0.42±0.22 D,P:<0.001). The AoA increased (3.23±0.74D to 3.92±0.93D,P:0.005), and DoF widened (0.72±0.18D to 0.81±0.26D,P:0.038). No change in ocular biometry parameters was observed. The change in DCNVA showed strong positive correlations with change in near add (r: 0.84,P:<0.001) and AoA (r: 0.66,P:0.04). Adverse effects were mild and did not lead to discontinuation.ConclusionPilocarpine 1.25% eye drops demonstrated statistically significant improvements in DCNVA, near add, AoA, and DoF after one month of treatment. Pilocarpine 1.25% eye drops shown increase in the amplitude of accommodation and depth of focus; without any significant change in ocular biometry parameters. The use of pilocarpine 1.25% eye drops can be an alternative intervention for enhancing near vision acuity of presbyopic subjects.