bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TGF-β–dominant chemoresistant phenotype of hepatoblastoma associated with aflatoxin exposure in children
Authors: Xiang Xiao , Hao Yijie , Cheng Cheng , Hu Huanjing , Chen Huadong , Tan Jiehui , Wang Yuanqi , Liu Xiaofei , Peng Bo , Liao Junbin , Wang Ji , Xie Yubin , liu Juncheng , Chen Shuling , Xu Lixia , Xie Wenxuan , Xue Ruidong , Kuang Ming , Xu Zhe , Jiang Hong , Peng Sui 
Published: July 2023

Background and Aims:
Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children’s health. Chemoresistance is the leading cause of mortality in patients with HB. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need.

Approach and Results:
We performed an integrative analysis including single-cell RNA sequencing, whole-exome sequencing, and bulk RNA sequencing in 180 HB samples, to reveal genomic features, transcriptomic profiles, and the immune microenvironment of HB. Multicolor immunohistochemistry staining and in vitro experiments were performed for validation. Here, we reported four HB transcriptional subtypes primarily defined by differential expression of transcription factors. Among them, the S2A subtype, characterized by strong expression of progenitor (MYCN, MIXL1) and mesenchymal transcription factors (TWIST1, TBX5), was defined as a new chemoresistant subtype. The S2A subtype showed increased TGF-β cancer-associated fibroblast and an immunosuppressive microenvironment induced by the upregulated TGF-β of HB. Interestingly, the S2A subtype enriched SBS24 signature and significantly higher serum aflatoxin B1-albumin (AFB1-ALB) level in comparison with other subtypes. Functional assays indicated that aflatoxin promotes HB to upregulate TGF-β. Furthermore, clinical prognostic analysis showed that serum AFB1-ALB is a potential indicator of HB chemoresistance and prognosis.

Conclusions:
Our studies offer new insights into the relationship between aflatoxin and HB chemoresistance and provide important implications for its diagnosis and treatment.
Venous Thromboembolism in Pediatric Inflammatory Bowel Disease: A Scoping Review
Authors: Gandhi Jermie , Mages Keith , Kucine Nicole , Chien Kimberley 
Published: July 2023

Objectives:
In addition to gastrointestinal symptoms, pediatric inflammatory bowel disease (pIBD) may present with extra-intestinal manifestations including venous thromboembolism (VTE). Prevention and treatment guidelines for VTE in pediatric patients are needed. In this scoping review, we sought to detail the available data on the prevention and management of VTE in pIBD.

Methods:
Using PRISMA extension for Scoping Reviews (PRISMA-ScR), we identified, screened, graded quality of, and analyzed, literature on VTE in pediatric IBD, published between 1967 and 2023.

Results:
Data were extracted from 107 studies (including 216 patients). IBD patients with VTE had a median age of 14 years. Children with VTE more frequently had ulcerative colitis (70%, n = 216), developed their VTE within the first year of IBD diagnosis (52%, n = 97), had recent steroid use (62%, n = 50), and had central venous catheters (38%, n = 42). Cerebral venous sinus thrombus was the most common VTE type (34% of all VTE). Testing for thrombophilia conditions was rarely available but 65% (n = 23) of subjects tested had elevated Factor VIII activity. While most patients made a full recovery, 5% (n = 11) died secondary to their VTE.

Conclusions:
While randomized clinical trials assessing interventions to prevent and treat VTE in pIBD would be ideal, the feasibility of doing such studies is low. However, there has been an increase in interest in this topic and an increase in literature over the past decade. As such, a consensus statement from a multidisciplinary group of experts based on available literature and clinical experience would be valuable for practicing clinicians.
The Risks and Benefits of Monoclonal Antibody Therapy During Pregnancy and Postpartum: Maternal, Obstetric, and Neonatal Considerations
Authors: Wickenheisser Natalie E. , Craig Amanda M. , Kuller Jeffrey A. , Dotters-Katz Sarah K. 
Published: July 2023

Importance
Autoimmune and rheumatologic conditions can lead to multiple adverse maternal, obstetric, and neonatal outcomes, especially if they flare during pregnancy. Although many medications to control these conditions exist, concerns regarding their safety often unnecessarily limit their use.

Objective
We aim to review the current evidence available describing the use of monoclonal antibody (mAb) therapeutics in pregnancy and postpartum and understand the impact of their use on the developing fetus and neonate.

Evidence Acquisition
Original research articles, review articles, case series and case reports, and pregnancy guidelines were reviewed.

Results
Multiple retrospective (including 1924 patients) and prospective studies (including 899 patients) of anti–tumor necrosis factor (TNF) agent use in pregnancy found no significant increase in rates of miscarriage, preterm birth, or congenital anomalies compared with controls. Most societies, including American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine, recommend initiation or continuation of TNF-α inhibitors during pregnancy for patients with autoimmune diseases. An increased risk of mild infections in newborns has been reported, although infections requiring hospitalizations are rare. Data suggest that breastfeeding while taking anti-TNF agents is safe for neonates. Less data exist for the use of other mAbs including anticytokine, anti-integrin, and anti–B-cell agents during pregnancy and postpartum.

Conclusions and Relevance
Current evidence suggests that the use of mAbs, particularly anti-TNF agents, is safe in pregnancy and postpartum, without significant adverse effects on the pregnant patient or infant. The benefits of ongoing disease control in pregnant patients result in favorable maternal and neonatal outcomes.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After participating in this activity, the provider should be better able to explain the benefits of using mAb therapies or biologics in pregnant patients; discuss the known and theoretical risks of using mAb therapies during pregnancy on neonates; and describe the risks and benefits of continuing mAb therapy while breastfeeding.
Prescription Opioid Use for Acute Pain and Persistent Opioid Use After Gynecologic Surgery: A Systematic Review
Authors: Matteson Kristen A. , Schimpf Megan O. , Jeppson Peter C. , Thompson Jennifer C. , Gala Rajiv B. , Balgobin Sunil , Gupta Ankita , Hobson Deslyn , Olivera Cedric , Singh Ruchira , White Amanda B. , Balk Ethan M. , Meriwether Kate V. ,   for the Society of Gynecologic Surgeons Systematic Review Group
Published: July 2023

(Abstracted from Obstet Gynecol 2023;141:681–696)
Although opioid analgesics can be an effective pain control method in the acute postoperative period, their use comes with risks such as opioid misuse, persistent use, or opioid use disorders. As most postsurgical patients use less than half of their prescribed opioids (and rarely dispose of unused medication), millions of legitimately prescribed opioid tablets are available for diversion and misuse annually.
Endoscopic Surveillance for Colorectal Cancer in Pediatric Ulcerative Colitis: A Survey Among Dutch Pediatric Gastroenterologists
Authors: Jagt Jasmijn Z. , van Schie Daniëlle A. , Benninga Marc A. , van Rheenen Patrick F. , de Boer Nanne K. H. , de Meij Tim G. J. ,   on behalf of the Kids with Crohn’s, Colitis (KiCC) Working Group for Collaborative Paediatric IBD Research in the Netherlands
Published: July 2023

Objectives:
This study aimed to evaluate the current clinical practice of Dutch pediatric gastroenterologists regarding the surveillance for colorectal dysplasia and cancer in pediatric ulcerative colitis (UC), including adherence to guidelines, the initiation and interval of surveillance and applied endoscopy techniques.

Methods:
A clinical vignette-based survey was distributed among all 47 pediatric gastroenterologists who are registered and working in the Netherlands.

Results:
Thirty-three pediatric gastroenterologists treating children with UC, completed the questionnaire (response rate 70%). Of these respondents, 23 (70%) do conduct endoscopic surveillance in their UC patients. Adherence to any of the available guidelines was reported by 82% of respondents. Twenty-four of 31 respondents (77%) indicated the need for development of a new guideline. Profound variation was witnessed concerning the initiation and interval of surveillance, and risk factors taken into consideration, such as disease extent and concomitant diagnosis of primary sclerosing cholangitis (PSC). The available national and European guidelines recommend the use of chromoendoscopy in the performance of surveillance. This technique was conducted by 8% of respondents, whereas 50% conducted conventional endoscopy with random biopsies.

Conclusions:
The heterogeneity in surveillance practices underlines the need for consistency among the guidelines, explicitly stated by 77% of the respondents. For this, future research on surveillance in pediatric UC is warranted, focusing on the risk of UC-associated colorectal cancer related to risk factors and optimal endoscopy techniques.
Pessary Management Approach Affects Likelihood of Surgery
Authors: Chen Yufan Brandon , Lowe Christian , Wozniak Amy , Pham Thythy T. , Fitzgerald Colleen M. , Mueller Elizabeth R. , Acevedo-Alvarez Marian 
Published: July 2023

Importance
It is unknown whether the pessary management type influences the need for surgery.

Objective
The aim of this study was to evaluate the rate of surgical treatment for pelvic organ prolapse or stress urinary incontinence with the type of pessary management (self-management or office management).

Study Design
We conducted a retrospective cohort study that included first-time pessary users treated at a tertiary urogynecologic clinic from 2012 to 2014 for pelvic organ prolapse, stress urinary incontinence, or both. For the primary outcome, we explored the relationship between pessary management type and the likelihood of surgery using multivariable Cox proportional hazards models. Secondary outcomes assessed relationships between patient factors (eg, demographics and clinical attributes) and pessary management type using multivariable logistics regression models.

Results
There were 218 patients included in our analysis. Of all pessary users, 59 (27.1%) required office management and 159 (72.9%) participated in self-management. Surgery was performed in 22 (35.1%) office-managed patients and 33 (19.3%) self-managed patients. Women who self-managed their pessaries were significantly less likely to undergo surgery than those who received office management (multivariable hazards ratios, 0.416; P = 0.005). In the multivariable logistic regression model for pessary management type, increasing age (odds ratio [OR], 1.098; P ≤ 0.0001), increasing body mass index (OR, 1.078; P < 0.05), and increasing genital hiatus (OR, 1.547; P < 0.05) were associated with increased odds of pessary office management compared with self-management.

Conclusions
In a urogynecology clinic setting, pessary self-management is associated with lower rates of surgical treatment compared with office management. Factors associated with office management include increased age, body mass index, and large genital hiatus.
Outcomes of Pessary Use at 1 Year in Women Treated for Pelvic Organ Prolapse in a Large Multicenter Registry
Authors: Yurteri-Kaplan Ladin A. , Meyn Leslie , Moalli Pam A. , Bradley Catherine S. , Foster Raymond T. , Andy Uduak U. , Guaderrama Noelani , Gutman Robert E. , Anger Jennifer T. , Hull Amy , Propst Katie , Shippey Stuart S. , Brown Heidi W. 
Published: July 2023

Importance
There is a lack of high-quality long-term follow-up regarding pessary treatment. Most studies are case series or retrospective with a small sample size and short-term follow-up.

Objectives
This study aimed to evaluate differences in women who continue versus discontinue pessary use and the effectiveness, quality of life, and safety associated with pessary management at 1 year.

Study Design
This study analyzed a multicenter national registry following women for 3 years with vaginal prolapse treated with a pessary or surgery. The primary outcome of this analysis was to compare the difference in characteristics among those who continue versus discontinue pessary use at 12 months.

Results
Among 1,153 participants enrolled, 376 (32.6%) opted for a pessary, and 296 (78.7%) were successfully fitted. Data were available for 240 participants (81%). At 1 year, 62% (n = 148) were still using pessaries, and 38% (n = 92) had stopped with 25% opting for surgery. Most commonly reported de novo adverse effects were urinary leakage (16%), feeling or seeing a bulge (12%), and vaginal discharge (11%). There was no difference in baseline characteristics among women who continued versus discontinued pessary use. At 12 months, subjective symptoms were similar between groups, with similar change in symptoms from baseline on most validated instruments. Those who continued to use a pessary reported worse urinary symptoms due to de novo urinary leakage (P = 0.01).

Conclusions
At 1 year, most women successfully fitted with a pessary continued pessary use. Although there was a significant improvement in condition-specific quality of life and low rates of complications, approximately 40% of women discontinued pessary use by 12 months. We were unable to identify any baseline characteristics associated with pessary discontinuation.
MosaiCatcher v2: a single-cell structural variations detection and analysis reference framework based on Strand-seq
Authors: Weber Thomas , Cosenza Marco Raffaele , Korbel Jan 
Published: July 2023

SummarySingle-cell DNA template strand sequencing (Strand-seq) allows a range of various genomic analysis including chromosome length haplotype phasing and structural variation (SV) calling in individual cells. Here, we present MosaiCatcher v2, a standardised workflow and reference framework for single-cell SV detection using Strand-seq. This framework introduces a range of functionalities, including: an automated upstream Quality Control (QC) and assembly sub-workflow that relies on multiple genome assemblies and incorporates a multistep normalisation module, integration of the scNOVA SV functional characterization and of the ArbiGent SV genotyping modules, platform portability, as well as a user-friendly and shareable web report. These new features of MosaiCatcher v2 enables reproducible computational processing of Strand-seq data, which are increasingly used in human genetics and single cell genomics, towards production environments.Availability and ImplementationMosaicatcher v2 is a standardised workflow, implemented using the Snakemake workflow management system. The pipeline is available on GitHub:https://github.com/friendsofstrandseq/mosaicatcher-pipeline/and on the snakemake-workflow-catalog:https://snakemake.github.io/snakemake-workflow-catalog/?usage=friendsofstrandseq/mosaicatcher-pipeline.Contactjan.korbel@embl.deSupplementary informationSupplementary data are available at Bioinformatics online.
Ischaemic Preconditioning attenuates Chronic Renal Damage following Ischaemia Reperfusion Injury
Authors: Brown Charlotte Victoria Maynard , Pino-Chavez Gilda , Zaidi Aeliya , Grigorieva Irina , Woods Emma , Steadman Robert , Chavez Rafael , Meran Soma , Khalid Usman 
Published: July 2023

ABSTRACTAcute Kidney Injury (AKI) is a common cause of Chronic Kidney Disease (CKD). The leading cause of AKI worldwide is Ischaemia Reperfusion Injury (IRI), seen most commonly in the clinical setting as a result of sepsis-driven hypotension. We are increasingly recognising, however, that AKI and CKD are one closely associated continuum of disease, rather than distinct entities. Ischaemic Preconditioning (IPC) is a strategy aimed at reducing the deleterious effects of IRI. This study demonstrates an efficacious model of kidney IRI, and the protective influence of IPC in attenuating renal injury/fibrosis.A rat model of bilateral kidney IRI was used: Male Lewis rats (n=84) were assigned to IRI, sham or IPC. In IRI, renal pedicles were clamped for 45 minutes. IPC groups underwent pulsatile IPC prior to IRI. Kidneys were retrieved at 24-hours, 48-hours, 7-days, 14-days and 28-days, and assessed histologically.IRI led to marked histological damage and renal fibrosis development by 28 days. Histological injury scores and degree of fibrosis were significantly increased following IRI and attenuated with IPC. IPC resulted in a 66% reduction in renal fibrosis at 28 days (p<0.001). IRI also led to a significant increase in serum creatinine acutely, which was attenuated by IPC (p<0.0001). Interestingly at 14-days, there was limited histological damage and differentiation between IRI and IPC kidneys was difficult.IPC can protect from both acute and chronic kidney damage. 14-days post IRI represents a transitional phase, which maybe a timepoint for commitment to either fibrosis or recovery, and hence offers potential for therapeutic intervention.
Extended lifespan in femaleDrosophila melanogasterthrough late-life caloric restriction
Authors: Li Michael , Macro Jacob , Huggins Billy J. , Meadows Kali , Mishra Dushyant , Martin Dominique , Rogina Blanka 
Published: July 2023

AbstractCalorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in femaleDrosophila melanogasteraged on a high calorie diet. This shift results in rapid decrease in mortality rate and extends fly lifespan. In contrast, shifting female flies from a low to a high calorie diet leads to a rapid increase in mortality and shorter lifespan. These changes are mediated by immediate metabolic and physiological adaptations. One of such adaptation is rapid adjustment in egg production, with flies directing excess energy towards egg production when shifted to a high diet, or away from reproduction in females shifted to low caloric diet. However, lifelong female fecundity reveals no associated fitness cost due to CR when flies are shifted to a high calorie diet. In view of high conservation of the beneficial effects of CR on physiology and lifespan in a wide variety of organisms, including humans, our findings could provide valuable insight into CR applications that could provide health benefits later in life.
Precise Nanopore Signal Modeling Improves Unsupervised Single-Molecule Methylation Detection
Authors: Boža Vladimír , Batmendijn Eduard , Perešíni Peter , Hodorová Viktória , Lichancová Hana , Rabatin Rastislav , Brejová Broňa , Nosek Jozef , Vinař Tomáš 
Published: July 2023

AbstractBase calling in nanopore sequencing is a difficult and computationally intensive problem, typically resulting in high error rates. In many applications of nanopore sequencing, analysis of raw signal is a viable alternative. Dynamic time warping (DTW) is an important building block for raw signal analysis. In this paper, we propose several improvements to DTW class of algorithms to better account for specifics of nanopore signal modeling. We have implemented these improvements in a new signal-to-reference alignment tool Nadavca. We demonstrate that Nadavca alignments improve unsupervised methylation detection over Tombo. We also demonstrate that by providing additional information about the discriminative power of positions in the signal, an otherwise unsupervised method can approach the accuracy of supervised models.Availability and implementationNadavca is available under MIT license athttps://github.com/fmfi-compbio/nadavca. Nanopore sequencing data sets are available from ENA bioproject PRJEB64246.Jaminaea angkorensisreference genome assembly is available from Zenodohttps://doi.org/10.5281/zenodo.8145315.
Explanation of saltatory conduction in myelinated axons and of micro-saltatory conduction in C fibers of pain sensation by a wave-type ion plasmonic mechanism of stimulus kinetics
Authors: Jacak J. E. , Jacak W. A. 
Published: July 2023

AbstractIon plasmon-polariton model of stimulus in myelinated axons and in C fibers of pain sensation is developed. This solves a long standing problem in neuroscience of by 2 − 3 orders of magnitude discrepancy between the observed fast speed of the saltatory conduction in myelinated axons or in C fibers with the upper limit of diffusive ion current velocity in these axons. The latter, described in the framework of so-called cable model, is too low in axons because of poor conductivity of neuron inner cytosol. The compliance with observations has been achieved upon plasmonic model of ionic local oscillations synchronized in periodically corrugated axons and propagating with high speed in the form of wave-type plasmon-polariton without any net diffusion current, thus not limited by resistivity. The new model of stimulus in myelinated axons reveals the different controlling role of myelin than previously thought from cable model. The control mechanism in non-myelinated C fibers is also proposed in agreement with observations. Recognition of plasmon model of neural signaling may be important for identifying a new targets for the future treatment at demyelination diseases and for fighting pain.
tfboot: Bootstrapping and statistical analysis for transcription factor binding site-disrupting variants in gene sets
Authors: Turner Stephen D. , Morrill Kathleen , Gedman Gregory , Titus Alexander J. 
Published: July 2023

AbstractMotivationGenetic variants in noncoding regions can drive changes in phenotype disrupting transcription factor binding site (TFBS) motifs. Other tools including motifbreakR have been developed to assess the impact of TFBS-disrupting variants. Here we introduce the tfboot package for statistically evaluating the TFBS disruption across asetof variants in upstream promoter regions.ResultsThe tfboot package builds on motifbreakR, plyranges, and GenomicRanges to provide methods for bootstrapping TFBS disruption to statistically quantify the impact across gene sets of interest compared to an empirical null distribution. We demonstrate the analysis here on variants in the elephant genome. The tfboot package readily integrates with Bioconductor and tidyverse-based workflows.AvailabilityThe tfboot package is implemented as an R package and is released under the MIT license athttps://github.com/colossal-compsci/tfboot.