bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative analysis of perioperative complications and biochemical recurrence between standard and extended pelvic lymph node dissection in prostate cancer patients undergoing radical prostatectomy: a systematic review and meta-analysis
Authors: Ding Guixin , Tang Gonglin , Wang Tianqi , Zou Qingsong , Cui Yuanshan , Wu Jitao 
Published: December 2023

Introduction:
Pelvic lymph node dissection (PLND) is commonly performed during radical prostatectomy (RP) for prostate cancer staging. This study aimed to comprehensively analyze existing evidence compare perioperative complications associated with standard (sPLND) versus extended PLND templates (ePLND) in RP patients.

Methods:
A meta-analysis of prospective studies on PLND complications was conducted. Systematic searches were performed on Web of Science, Pubmed, Embase, and the Cochrane Library until May 2023. Risk ratios (RRs) were estimated using random-effects models in the meta-analysis. The statistical analysis of the data was carried out using Review Manager software.

Results:
Nine studies, including three randomized clinical trial and six prospective studies, with a total of 4962 patients were analyzed. The meta-analysis revealed that patients undergoing ePLND had a higher risk of partial perioperative complications, such as lymphedema (I
2=28%; RR 0.05; 95% CI: 0.01–0.27; P<0.001) and urinary retention (I
2=0%; RR 0.30; 95% CI: 0.09–0.94; P=0.04) compared to those undergoing sPLND. However, there were no significant difference was observed in pelvic hematoma (I
2=0%; RR 1.65; 95% CI: 0.44–6.17; P=0.46), thromboembolic (I
2=57%; RR 0.91; 95% CI: 0.35–2.38; P=0.85), ureteral injury (I
2=33%; RR 0.28; 95% CI: 0.05–1.52; P=0.14), intraoperative bowel injury (I
2=0%; RR 0.87; 95% CI: 0.14–5.27; P=0.88), and lymphocele (I
2=0%; RR 1.58; 95% CI: 0.54–4.60; P=0.40) between sPLND and ePLND. Additionally, no significant difference was observed in overall perioperative complications (I
2=85%; RR 0.68; 95% CI: 0.40–1.16; P=0.16). Furthermore, ePLND did not significantly reduce biochemical recurrence (I
2=68%; RR 0.59; 95% CI: 0.28–1.24; P=0.16) of prostate cancer.

Conclusion:
This analysis found no significant differences in overall perioperative complications or biochemical recurrence between sPLND and ePLND, but ePLND may offer enhanced diagnostic advantages by increasing the detection rate of lymph node metastasis.
Uropathogenic Dysbiosis Pattern is Associated With Urethral Fibrosis
Authors: Witthaus Michael , Chawla Saager , Puri Dhruvi , Sakamoto Kyoko , Buckley Jill , Miller Aaron , Rajasekaran Mahadevan 
Published: December 2023

Purpose:
Cellular mechanisms of stricture progression after repeated transurethral interventions are unclear. We hypothesize that urethral injury and mechanical stretch cause tears on the urethral epithelial cell lining leading to leaking epithelium and urine extravasation. Urinary bacteria traverse the epithelial lining and may promote fibrogenesis through inflammation due to microbial activity. Our objective was to perform a case-control study of the urobiome from patients with urethral stricture disease or healthy controls using 16S rRNA and shotgun metagenomic sequencing profiling to elucidate the clinical relevance of the urobiome in urinary stricture progression.

Materials and Methods:
First catch urine samples from patients and healthy volunteers were collected and pelleted urine was used for DNA extraction, followed by high throughput 16S rRNA and shotgun metagenomic sequencing. Sequencing data were used to determine microbial taxa and functions associated with urethral stricture disease.

Results:
Sequencing results revealed that the lower urinary tract urobiome was significantly different between urethral stricture disease cases and healthy controls. In particular, taxonomic and metabolic profiles point toward anaerobic biofilm formation by antibiotic-resistant species of Klebsiella, which is a known uropathogen. Importantly, no patients in the study exhibited signs or symptoms of clinical infection.

Conclusions:
Our findings suggest a role for biofilm formation by uropathogens such as Klebsiella spp. in developing an inflammatory environment and consequent fibrosis progression. Future studies will elucidate specific mechanisms of Klebsiella-induced fibrosis. Our data suggest that targeting specific bacteria or biofilm formation may be beneficial for urethral stricture disease detection and prevention of progression.
The association between anticholinergic/sedative burden and physical frailty in people aging with HIV
Authors: Michael Henry Ukachukwu , Brouillette Marie-Josée , Tamblyn Robyn , Fellows Lesley K. , Mayo Nancy E. 
Published: December 2023

Objective:
This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV.

Design:
This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study.

Methods:
Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype (FFP) based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs).

Results:
Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22–1.32; 95% confidence interval (CI) range: 1.03–1.66), sedative burden (OR range: 1.18–1.24; 95% CI range: 1.02–1.45), high anticholinergic burden (OR range: 2.12–2.74; 95% CI range: 1.03–6.19), and high sedative burden (OR range: 1.94–2.18; 95% CI: 1.01–4.34).

Conclusion:
The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods.
18F-FDG PET/CT Imaging of Prostatic Epithelioid Hemangioendothelioma
Authors: Deng Yan , Deng Yujiao , He Limeng , Zhang Wei , Lei Xiaoping 
Published: December 2023

Abstract
Epithelioid hemangioendothelioma of the prostate is a rare malignant vasogenic tumor. We report a case of epithelioid hemangioendothelioma of the prostate in a 65-year-old man with lymph nodes and lung metastases on 18F-FDG PET/CT imaging. The patient presented with symptoms of frequent and urgent urination. On 18F-FDG PET/CT, intense FDG uptake was observed in the prostate mass along with multiple FDG-avid lesions involving the lung and lymph nodes. Histopathological examination confirmed epithelioid hemangioendothelioma in both the prostate mass and lung nodule.
Evaluation of a STAT MRI Protocol for Patients with Optic Disc Edema
Authors: Gibbons Alison B. , Huang Peng , Sklar Matthew , Kim Philip , Henderson Amanda D. 
Published: December 2023

Background:
Evaluating patients with potentially sight-threatening conditions frequently involves urgent neuroimaging, and some providers recommend expediting emergency department (ED) evaluation. However, several factors may limit the practicality of ED evaluation. This pilot study assessed the feasibility and safety of a STAT magnetic resonance imaging (MRI) protocol, designed to facilitate outpatient MRI within 48 hours of referral, compared with ED evaluation for patients with optic disc edema.

Methods:
A retrospective chart review was performed. Demographics, clinical data, and baseline ophthalmic measures were compared between patients in STAT and ED groups using the t test or Fisher exact test. Multivariate analyses compared changes in visual acuity (VA), visual field mean deviation (VF MD), retinal nerve fiber layer thickness, and edema grade between presentation and follow-up using a mixed-effects model adjusting for age, sex, and baseline measures.

Results:
A total of 70 patients met the study criteria—24 (34.3%) in the STAT MRI cohort and 46 (65.7%) in the ED cohort. Demographic variables were similar between groups. Patients referred to the ED had worse VA (P < 0.001), larger VF MD (P < 0.001), and higher edema grade (P = 0.002) at presentation. Four patients in the ED group and none in the STAT group were found to have space-occupying lesions. Multivariate analyses showed that follow-up measures were significantly associated with their baseline values (all P < 0.001) but not with referral protocol (all P > 0.099). The STAT MRI protocol was associated with lower average patient charges and hospital costs.

Conclusions:
The STAT MRI protocol did not result in inferior visual outcomes or delay in life-threatening diagnoses. Urgent outpatient evaluation, rather than ED referral, seems safe for some patients with optic disc edema. These findings support continued utilization of the protocol and ongoing improvement efforts.
The Effects of Preeclamptic Milieu on Cord Blood Derived Endothelial Colony-Forming Cells
Authors: Hall Eva , Alderfer Laura , Neu Erin , Saha Sanjoy , Johandes Ellie , Haas David M. , Haneline Laura S. , Hanjaya-Putra Donny 
Published: December 2023

AbstractPreeclampsia is one of the leading causes of infant and maternal mortality worldwide. Many infants born from preeclamptic pregnancies are born prematurely with higher risk of developing cardiovascular later in their life. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). To gain insight into this, cord blood derived ECFCs isolated from preeclamptic pregnancies (PRECs) were analyzed and compared to their healthy counterparts. While PRECs preserve key endothelial markers, they upregulate several markers associated with oxidative stress and inflammatory response. Compared to ECFCs, PRECs also exhibit lower migratory behaviors and impaired angiogenic potential. Interestingly, treatment of neuropilin-1 can improve tube formationin vitro. Collectively, this study reports that preeclamptic milieu influence phenotypes and functionality of PRECs, which can be rejuvenated using exogenous molecules. Promising results from this study warrant future investigations on the prospect of the rejuvenated PRECs to improve lung function of infants born from preeclamptic pregnancies.
MARK1 regulates dendritic spine morphogenesis and cognitive functionsin vivo
Authors: Kelly-Castro Emily C. , Shear Rebecca , Dindigal Ankitha H. , Bhagwat Maitreyee , Zhang Huaye 
Published: December 2023

AbstractDendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and theMARK1gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, thein vivorole of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) ofMark1causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found that MARK1 cKO mice show defects in spatial learning in the Morris Water Maze and reduced anxiety-like behaviors in the Elevated Plus Maze. Furthermore, we found loss of MARK1 causes synaptic accumulation of GKAP and GluR2. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functionsin vivo.
Advancing childhood cancer research through young investigator and advocate collaboration
Authors: Weiner Amber K. , Palmer Antonia , Moll Melanie Frost , Lindberg Gavin , Reidy Kevin , Diskin Sharon J. , Mackall Crystal L. , Maris John M. , Sullivan Patrick J. 
Published: December 2023

AbstractCancer advocates and researchers share the same goal of driving science forward to create new therapies to cure more patients. The power of combining cancer researchers and advocates has become of increased importance due to their complementary expertise. Therefore, advocacy is a critical component of grant structures and has become embedded into the Stand Up 2 Cancer (SU2C) applications. To date, the optimal way to combine these skillsets and experiences to benefit the cancer community is currently unknown. The Saint Baldrick’s Foundation (SBF)–SU2C now called St. Baldrick’s Empowering Pediatric Immunotherapies for Childhood Cancer (EPICC) Team is comprised of a collaborative network across nine institutions in the United States and Canada. Since SU2C encourages incorporating advocacy into the team structure, we have assembled a diverse team of advocates and scientists by nominating a young investigator (YI) and advocate from each site. In order to further bridge this interaction beyond virtual monthly and yearly in person meetings, we have developed a questionnaire and conducted interviews. The questionnaire is focused on understanding each member’s experience at the intersection between science/advocacy, comparing to previous experiences, providing advice on incorporating advocacy into team science and discussing how we can build on our work. Through creating a YI and advocate infrastructure, we have cultivated a supportive environment for meaningful conversation that impacts the entire research team. We see this as a model for team science by combining expertise to drive innovation forward and positively impact pediatric cancer patients, and perhaps those with adult malignancies.SignificanceQuestionnaire results show both advocates and YI’s see this structure to be valuable and beneficial. YI’s communicated their research to a non-scientific audience and learned advocate’s experience. This was their first advocacy experience for most YIs. Advocates learned more about the research being conducted to provide hope. They can also aid with fundraising, publicity and lobbying. This collaboration improves science communication, designing patient-friendly clinical trials and sharing experience across institutions.
Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters
Authors: Reddy Krishna D. , Rasool Burha , Akher Farideh Badichi , Kutlešić Nemanja , Pant Swati , Boudker Olga 
Published: December 2023

AbstractSecondary active membrane transporters harness the energy of ion gradients to concentrate their substrates. Homologous transporters evolved to couple transport to different ions in response to changing environments and needs. The bases of such diversification, and thus principles of ion coupling, are unexplored. Employing phylogenetics and ancestral protein reconstruction, we investigated sodium-coupled transport in prokaryotic glutamate transporters, a mechanism ubiquitous across life domains and critical to neurotransmitter recycling in humans. We found that the evolutionary transition from sodium-dependent to independent substrate binding to the transporter preceded changes in the coupling mechanism. Structural and functional experiments suggest that the transition entailed allosteric mutations, making sodium binding dispensable without affecting ion-binding sites. Allosteric tuning of transporters’ energy landscapes might be a widespread route of their functional diversification.
BayesAge: A Maximum Likelihood Algorithm To Predict Epigenetic Age
Authors: Mboning Lajoyce , Rubbi Liudmilla , Thompson Michael , Bouchard Louis-S. , Pellegrini Matteo 
Published: December 2023

ABSTRACTDNA methylation is a reaction that results in the formation of 5-methylcytosine when a methyl group is added to the cytosine’s C5 position. As organisms age, DNA methylation patterns change in a reproducible fashion. This phenomenon has established DNA methylation as a valuable biomarker in aging studies. Epigenetic clocks based on weighted combinations of methylation sites have been developed to accurately predict the age of an individual from their methylome. However, many epigenetic clocks, particularly those that utilize penalized regression, model the changes in methylation linearly with age. Moreover, these models, which use methylation levels as features, are not robust to missing data and do not account the count-based nature of bisulfite sequence data. Additionally, the models are generally not interpretable. To overcome these challenges, we present BayesAge, an extension of the previously developed scAge approach that was developed for the analysis of single cell DNA methylation datasets. BayesAge utilizes maximum likelihood estimation (MLE) to infer ages, models count data using binomial distributions, and uses LOWESS smoothing to capture the non-linear dynamics between methylation and age. Our approach is designed for use with bulk bisulfite sequencing datasets. BayesAge outperforms scAge in several respects. Specifically, BayesAge’s age residuals are not age associated, thus providing a less biased representation of epigenetic age variation across populations. Moreover, BayesAge enables the estimation of error bounds on age inference and, when run on down-sampled data, its coefficient of determination between predicted and actual ages surpasses both scAge and penalized regression.
Increased susceptibility for pathogenesis of post-traumatic epilepsy in offspring exposed to deltamethrin during gestation and ameliorative effects of dietary curcumin
Authors: Kumar Prince , Kumar Kamendra , Sharma Deepak 
Published: December 2023

AbstractDeltamethrin (DLT) is a most potent and widely used pesticide that does not cross Blood Brain Barrier (BBB) in adults. While it considered as safe, its lipophilic properties makes it a neurotoxic substance specially in early stages of brain development. It has shown neurotoxic effects on the brain by hyper-excitation of neurons. Epilepsy is a neurological disorder with recurring seizures where epileptogenesis occurs due to hyperexcitation of neurons. In various kinds of epilepsy, post-traumatic epilepsy (PTE) is a common epilepsy in children due to traumatic brain injury (TBI). PTE, however reportedly alleviated by curcumin in rats. Therefore, in the current study, we assessed the effect of gestational DLT exposure on the severity of PTE. The pregnant rats were injected with 0.75mg/kg-b/w of DLT dissolved in 1% DMSO each day of gestation between days 7-15. Epilepsy was induced four months postnatally, and curcumin was orally administered by oral gavage. ECoG, behavioral tests, Golgi Staining, immunofluorescence, and immunohistochemistry was performed to assess the pathogenesis, severity of epilepsy, and mitigating effects of curcumin. The results indicated the neurotoxic effects of DLT by raising the severity of seizures in an electrophysiological and behavioral manner. PTE decreased the dendritic branching and arborization. Sodium channel overexpression is an important reason for the hyperexcitation of neurons during the pathogenesis of epilepsy. DLT enhanced the increase in expression of both sodium channel subunits NaV1.1 and NaV1.6 during epileptogenesis. Similarly, synaptic markers PSD95 and SYP decreased. Astrocytic and microglial activation increased during pathogenesis of PTE. The antiepileptic effects of curcumin alleviated the effects on electrobehavioral response, neuronal arborization, and levels of NaVs, PSD95, SYP, GFAP and Iba1 in epilepsy. However, DLT raised the severity and susceptibility of epilepsy and decreased the antiepileptic effects on gestationally DLT-exposed epileptic animals. Our result demonstrates the gestational neurotoxic exposure of DLT increased the severity and susceptibility for PTE while decreasing the antiepileptic effects of curcumin.
Saturation resistance profiling of EGFR variants against tyrosine kinase inhibitors using prime editing
Authors: Kim Younggwang , Oh Hyeong-Cheol , Lee Seungho , Kim Hyongbum Henry 
Published: December 2023

AbstractVariants of uncertain significance (VUS) hamper the clinical application of genetic information. For example, in treating lung cancer with tyrosine kinase inhibitors (TKIs), many epidermal growth factor receptor (EGFR) variants remain classified as VUS with respect to TKI sensitivity1,2. Such incomplete resistance profiles hinder clinicians from selecting optimal therapeutic agents3,4. A high-throughput approach that can evaluate the functional effects of single nucleotide variants (SNVs) could reduce the number of VUS. Here we introduce SynPrime, a method based on prime editing that enabled the generation and functional evaluation of 2,476 SNVs in theEGFRgene, including 99% of all possible variants in the canonical tyrosine kinase domain (exons 18 to 21). We determined resistance profiles of 95% (= 1,726/1,817) of all possible EGFR protein variants encoded in the whole tyrosine kinase domain (exons 18 to 24) against afatinib, osimertinib, and osimertinib in the presence of the co-occurring mutation T790M, in PC-9 cells. SynPrime, which uses direct sequencing of endogenous regions to identify SNVs, provided more accurate functional evaluations than a guide RNA abundance-based approach. Our study has the potential to substantially improve the precision of therapeutic choices in clinical settings and contribute to addressing the issue of VUS by being applied to other genes.
A Whole-Cell Screening Platform to Discover Cell Adhesion Molecules that Enable Programmable Bacterial Cell-Cell Adhesion
Authors: Chen Po-Yin , Chen Yung-Chih , Chen Po-Pang , Lin Kuan-Ting , Wang Wei-Le , Hsia Kuo-Chiang , Ting See-Yeun 
Published: December 2023

ABSTRACTDeveloping programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system—a contact-dependent DNA delivery nanomachine—we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as targeted antimicrobial interventions in the microbiome by deploying programmed inhibitor cells.