bluuebunny/crossref_metadata_2025_split huggingface dataset:
TSCRE: a comprehensive database for tumor-specific cis-regulatory elements
Authors: Peng Guanjie , Liu Bingyuan , Zheng Mohan , Zhang Luowanyue , Li Huiqin , Liu Mengni , Liang Yuan , Chen Tianjian , Luo Xiaotong , Shi Xianping , Ren Jian , Zheng Yueyuan 
Published: January 2024

Abstract
Cis-regulatory elements (CREs) and super cis-regulatory elements (SCREs) are non-coding DNA regions which influence the transcription of nearby genes and play critical roles in development. Dysregulated CRE and SCRE activities have been reported to alter the expression of oncogenes and tumor suppressors, thereby regulating cancer hallmarks. To address the strong need for a comprehensive catalogue of dysregulated CREs and SCREs in human cancers, we present TSCRE (http://tscre.zsqylab.com/), an open resource providing tumor-specific and cell type-specific CREs and SCREs derived from the re-analysis of publicly available histone modification profiles. Currently, TSCRE contains 1 864 941 dysregulated CREs and 68 253 dysregulated SCREs identified from 1366 human patient samples spanning 17 different cancer types and 9 histone marks. Over 95% of these elements have been validated in public resources. TSCRE offers comprehensive annotations for each element, including associated genes, expression patterns, clinical prognosis, somatic mutations, transcript factor binding sites, cancer-type specificity, and drug response. Additionally, TSCRE integrates pathway and transcript factor enrichment analyses for each study, enabling in-depth functional and mechanistic investigations. Furthermore, TSCRE provides an interactive interface for users to explore any CRE and SCRE of interest. We believe TSCRE will be a highly valuable platform for the community to discover candidate cancer biomarkers.
Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study
Authors: Pavel Marianne , Lahner Harald , Hörsch Dieter , Rinke Anja , Denecke Timm , Koch Arend , Regnault Benjamin , Helbig Dorit , Hoffmanns Philipp , Raderer Markus 
Published: January 2024

Abstract

Background
In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs.

Materials and Methods
SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN.

Results
Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication.

Conclusions
LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.
A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma
Authors: Durando Michael , Gopal Ajay K , Tuscano Joseph , Persky Daniel 
Published: January 2024

Abstract

Purpose
The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ionizing radiation. In 2002, the first RIT was approved by the U.S. Food and Drug Administration for the treatment of patients with indolent B-cell follicular non-Hodgkin lymphoma (NHL). The 2 approved agents, 90 Y-ibritumomab tiuxetan (90Y-IT, Zevalin, Acrotech Biopharma) and 131 I-tositumomab (131-IT, Bexxar, GlaxoSmithKline) both target CD20. The aim of this study was to review the clinical applications and supporting clinical trial data of anti-CD20 RIT for lymphoma.

Methods
A review of published articles and abstracts on the clinical efficacy and safety of 90Y-IT and iodine I 131 tositumomab was performed.

Results
The clinical efficacy and safety of anti-CD20 RIT have been demonstrated in numerous clinical trials and case series. Agents have produced significant responses in patients with follicular NHLs and in off-label applications. Importantly, RIT has demonstrated promising findings in high-risk lymphomas and heavily pretreated and refractory patient populations. Associated toxicity profiles are noted as tolerable, acceptable, and most often reversible.

Conclusions
In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course.
Solving inverse problems in physics by optimizing a discrete loss: Fast and accurate learning without neural networks
Authors: Karnakov Petr , Litvinov Sergey , Koumoutsakos Petros 
Published: January 2024

Abstract
In recent years, advances in computing hardware and computational methods have prompted a wealth of activities for solving inverse problems in physics. These problems are often described by systems of partial differential equations (PDEs). The advent of machine learning has reinvigorated the interest in solving inverse problems using neural networks (NNs). In these efforts, the solution of the PDEs is expressed as NNs trained through the minimization of a loss function involving the PDE. Here, we show how to accelerate this approach by five orders of magnitude by deploying, instead of NNs, conventional PDE approximations. The framework of optimizing a discrete loss (ODIL) minimizes a cost function for discrete approximations of the PDEs using gradient-based and Newton’s methods. The framework relies on grid-based discretizations of PDEs and inherits their accuracy, convergence, and conservation properties. The implementation of the method is facilitated by adopting machine-learning tools for automatic differentiation. We also propose a multigrid technique to accelerate the convergence of gradient-based optimizers. We present applications to PDE-constrained optimization, optical flow, system identification, and data assimilation. We compare ODIL with the popular method of physics-informed neural networks and show that it outperforms it by several orders of magnitude in computational speed while having better accuracy and convergence rates. We evaluate ODIL on inverse problems involving linear and nonlinear PDEs including the Navier–Stokes equations for flow reconstruction problems. ODIL bridges numerical methods and machine learning and presents a powerful tool for solving challenging, inverse problems across scientific domains.
Machine Learning as a Tool for Hypothesis Generation
Authors: Ludwig Jens , Mullainathan Sendhil 
Published: January 2024

Abstract
While hypothesis testing is a highly formalized activity, hypothesis generation remains largely informal. We propose a systematic procedure to generate novel hypotheses about human behavior, which uses the capacity of machine learning algorithms to notice patterns people might not. We illustrate the procedure with a concrete application: judge decisions about whom to jail. We begin with a striking fact: the defendant’s face alone matters greatly for the judge’s jailing decision. In fact, an algorithm given only the pixels in the defendant’s mug shot accounts for up to half of the predictable variation. We develop a procedure that allows human subjects to interact with this black-box algorithm to produce hypotheses about what in the face influences judge decisions. The procedure generates hypotheses that are both interpretable and novel: they are not explained by demographics (e.g., race) or existing psychology research, nor are they already known (even if tacitly) to people or experts. Though these results are specific, our procedure is general. It provides a way to produce novel, interpretable hypotheses from any high-dimensional data set (e.g., cell phones, satellites, online behavior, news headlines, corporate filings, and high-frequency time series). A central tenet of our article is that hypothesis generation is a valuable activity, and we hope this encourages future work in this largely “prescientific” stage of science.
Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury
Authors: Tremblay Jacob R , Ortiz Jose A , Quijano Janine C , Zook Heather N , Erdem Neslihan , LeBon Jeanne M , Li Wendong , Jou Kevin , Tsark Walter , Mann Jeffrey R , Kozlowski Mark T , Tirrell David A , Esni Farzad , Engle Dannielle D , Riggs Arthur D , Ku Hsun Teresa 
Published: January 2024

Abstract
Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.
Experimental and computational comparison of freeze–thaw-induced pressure generation in red and sugar maple
Authors: Zarrinderakht Maryam , Konrad Isabell , Wilmot Timothy R , Perkins Timothy D , van den Berg Abby K , Stockie John M 
Published: January 2024

Abstract
Sap exudation is the process whereby trees such as sugar (Acer saccharum Marsh.) and red maple (Acer rubrum L.) generate unusually high positive stem pressure in response to repeated cycles of freeze and thaw. This elevated xylem pressure permits the sap to be harvested over a period of several weeks and hence is a major factor in the viability of the maple syrup industry. The extensive literature on sap exudation documents competing hypotheses regarding the physical and biological mechanisms that drive positive pressure generation in maple, but to date, relatively little effort has been expended on devising mathematical models for the exudation process. In this paper, we utilize an existing model of Graf et al. (J Roy Soc Interface 12:20150665, 2015) that describes heat and mass transport within the multiphase gas–liquid–ice mixture in the porous xylem tissue. The model captures the inherent multiscale nature of xylem transport by including phase change and osmotic transport in wood cells on the microscale, which is coupled to heat transport through the tree stem on the macroscale. A parametric study based on simulations with synthetic temperature data identifies the model parameters that have greatest impact on stem pressure build-up. Measured daily temperature fluctuations are then used as model inputs and the resulting simulated pressures are compared directly with experimental measurements taken from mature red and sugar maple stems during the sap harvest season. The results demonstrate that our multiscale freeze–thaw model reproduces realistic exudation behavior, thereby providing novel insights into the specific physical mechanisms that dominate positive pressure generation in maple trees.
Prevalence and pattern of functional gastrointestinal disorders among secondary school adolescents in Lagos, Nigeria
Authors: Kumolu-Johnson Tolulope , Senbanjo Idowu Odunayo 
Published: January 2024

Abstract

Background
Limited data exist on functional gastrointestinal disorders (FGIDs) among sub-Saharan African children. This study aimed to determine FGID prevalence and pattern among secondary school adolescents in Lagos, Nigeria.

Methods
This descriptive cross-sectional study was conducted among adolescents aged 10–18 years in Isolo, Lagos, Nigeria from December 2020 to March 2021. A multi-stage sampling technique was used to select a total of 696 students from four secondary schools. Data were collected using a specifically designed questionnaire, the ROME IV questionnaire (QPGS-IV), and analyzed using the Statistical Package for the Social Sciences (SPSS) version 24.

Results
The mean age of the adolescents was 13.6 ± 2.1. A total of 221 (31.8%) adolescents fulfilled the criteria for at least one of the FGIDs. The most common FGIDs were functional constipation (10.1%), functional dyspepsia (9.4%) and abdominal migraine (8.6%). There was no significant difference in the overall prevalence of FGIDs between age groups (p = 0.07) and genders (p = 0.949). However, the prevalence of FGID sub-types showed that abdominal migraine, irritable bowel syndrome and functional non-retentive fecal incontinence were significantly higher in the age group 10–12 years (p = 0.045, p = 0.029 and p = 0.027, respectively) while only functional vomiting was significantly higher in male compared to female (p = 0.038).

Conclusion
FGIDs are common among adolescents in Lagos, Nigeria. The pattern of FGIDs shows similarities and differences with reports from other parts of the world. Healthcare workers must be aware of these disorders to provide optimal care.
Zone 2 5th Metatarsal Fractures Treated Nonoperatively Have Similar Time to Healing to Those Treated Operatively
Authors: Kadiyala Manasa L. , Kingery Matthew T. , Hamzane Mohamed , Walls Raymond , Ganta Abhishek , Konda Sanjit R. , Egol Kenneth A. 
Published: January 2024

OBJECTIVES:
To quantify the rate of union and time to clinical and radiographic healing in Zone 2 proximal 5th metatarsal (MT) fractures and compare these outcomes between Zone 2 fractures treated operatively and nonoperatively.

METHODS:

Design:
Retrospective cohort study

Setting:
Academic Level I Trauma Center

Patient Selection Criteria:
Patients with 5th metatarsal fractures who presented between December 2012 and April 2022 and confirmed to have Zone 2 fractures (defined as fractures entering the proximal 4-5 MT articulation on the oblique radiographic view) were included in the study analysis in either the operative or nonoperative cohort.

Outcome Measures and Comparisons:
Nonunion, time to clinical healing by, and time to radiographic healing between operative and nonoperative treatment

RESULTS:
Among the 499 included patients, 475 patients (95.2%) were initially treated nonoperatively, and 24 patients (4.8%) were treated operatively. Both groups were similar in demographics (Table 1). There was no difference in the proportion of patients with nonunions between groups (6.1% in the nonoperative group versus 3.8% in the operative group, p = 1.000). Additionally, there was no statistically significant difference between groups with respect to the time to clinical healing by (9.9 +/- 8.3 weeks for the nonoperative group versus 15.4 +/- 15.0 weeks for the operative group, p = 0.117) or the time to radiographic healing by (18.7 +/- 12 weeks for the nonoperative group versus 18.5 +/- 16.6 weeks for the operative group, p = 0.970) (Table 2).

CONCLUSIONS:
Zone 2 5th metatarsal base fractures were successfully treated with nonoperative management. There was no evidence in this study that operative treatment leads to significantly faster clinical or radiographic healing.
Two novel deep-learning models to predict spontaneous ureteral calculi passage: Model development and validation
Authors: Xiao Zhiying , Bai Hui , Zhang Yumeng 
Published: January 2024

Abstract

Objective
The aim of this study was to develop and evaluate two deep-learning (DL) models for predicting spontaneous ureteral stone passage (SSP).

Materials and methods
A total of 1217 patients with thin-layer computed tomography–confirmed ureteral stones in our hospital from January 2019 to December 2022 were retrospectively examined. These patients were grouped into 3 data sets: the training set (n = 1000), the validation set (n = 100), and the test set (n = 117). Two DL models based on residual neural network (ResNet)—2-dimensional (2D) ResNet29 and 3-dimensional (3D) ResNet29—were separately developed, trained, and assessed. The predictive ability of a conventional approach using a stone diameter of <5 mm on computed tomography was investigated, and the results were compared with those of the two DL models.

Results
Of the 1217 patients, SSP was reported in 446 (36.6%). The total accuracy, sensitivity, and specificity were 76.9%, 56.1%, and 90.8% for the stone diameter approach; 87.1%, 84.2%, and 92.7% for the 2D ResNet29 model; and 90.6%, 88.2%, and 95.1% for the 3D ResNet29 model, respectively. Both the 2D and 3D ResNet29 models showed significantly higher accuracy than the stone diameter approach. Receiver operating characteristic curve analysis showed that both DL models had a significantly higher area under the curve than the stone diameter–based classification.

Conclusions
The DL models, particularly the 3D model, are novel and effective methods for predicting SSP rates. Using such models may help determine whether a patient should receive surgical intervention or expect a long interval before stone passage.
Comparison of recovery profiles between total intravenous anaesthesia with propofol or remimazolam reversed with flumazenil in patients undergoing breast surgery
Authors: Lee Jaemoon , Kim Dong Hyouk , Ju Jae-Woo , Nam Karam , Cho Youn Joung , Jeon Yunseok , Lee Seohee 
Published: January 2024

BACKGROUND
Remimazolam, a short acting benzodiazepine, is being used for general anaesthesia. The results of studies comparing recovery after propofol with that of remimazolam are inconsistent. Given that flumazenil reverses the sedative effects of remimazolam, we hypothesised that it would speed up recovery from remimazolam general anaesthesia.

OBJECTIVES
The aim of this trial was to compare the speed of recovery from general anaesthesia between propofol and remimazolam reversed with flumazenil in patients undergoing minimally invasive breast surgery.

DESIGN
Randomised, single-centre, double-blind controlled trial.

SETTING
A tertiary teaching hospital in South Korea from August 2022 to December 2022.

PATIENTS
Adult patients (≥19 years of age) about to undergo general anaesthesia for scheduled breast cancer surgery.

INTERVENTIONS
Patients were randomly allocated to either the propofol or the remimazolam/flumazenil group. The emergence process was monitored by only one anaesthesiologist.

MAIN OUTCOME MEASURES
The primary outcome was the time to eye opening to command during recovery from the general anaesthesia. Time to removal of the supraglottic airway (SGA) time to discharge, and the Riker sedation agitation scale (SAS) score (1 to 4) during emergence were compared as secondary outcomes.

RESULTS
The remimazolam group had a significantly shorter mean time to eye opening than the propofol group [127 ± 51 vs. 314 ± 140 s; mean difference 187 s (95% confidence interval (CI), 133 to 241 s; P < 0.001]. The remimazolam group also had shorter times to SGA removal [169 ± 51 vs. 366 ± 149 s; mean difference 198 s (95% CI, 140 to 255 s); P < 0.001] and time to discharge from the operating room [243 ± 55 vs. 449 ± 159 s; mean difference 206 s (95% CI, 145 to 267 s); P < 0.001]. The SAS scores during emergence also differed significantly, with 1 patient in the propofol group and 25 in the remimazolam group attaining scores of 4 (P < 0.001).

CONCLUSION
Administration of remimazolam with flumazenil may be a promising option for patients undergoing breast cancer surgery, providing faster recovery and better SAS scores than propofol during emergence from general anaesthesia.

TRIAL REGISTRATION
ClinicalTrials.gov (NCT05435911).
Update on syphilis in pregnancy: marrying basic science advances and clinical perseverance to solve an ancient public health problem
Authors: Adhikari Emily H. 
Published: January 2024

Purpose of review
While the clinical disease of syphilis, its consequences in pregnancy, and its sensitivity to penicillin treatment have remained relatively unchanged for a century or more, new technologies and basic discoveries in syphilis research have translated into tangible advances in clinical diagnosis, treatment, and prevention. The purpose of this review is to help the reader understand some of the recent relevant scientific publications on syphilis and its causative organism in a clinical obstetric context.

Recent findings
Rates of adult and congenital syphilis have risen dramatically in the last decade despite public health efforts. Penicillin shortages and lack of screening or adequate treatment have all contributed to global disease burden. Advances in genomic and microbiological characterization of this spirochete have led to new developments in serologic and molecular diagnosis as well as evaluation of potential vaccine candidates. Until a syphilis vaccine is available, substance use disorders and lack of screening in pregnancy are associated with increased congenital syphilis, and these challenges will require novel solutions to fully address this public health crisis.

Summary
Addressing the burden of congenital syphilis demands that obstetricians stay well informed of new tools and resources for diagnosis, treatment, and prevention of syphilis now and in the future.