bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative Safety of Bladder Hydrodistention in Patients on Antithrombotic Therapy
Authors: Peng Liao , Wang Wei , Gao Xiao-shuai , Luo De-yi 
Published: March 2023

Importance
Bladder hydrodistention (BH) is commonly used to diagnose and treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS), but the overall assessment of bleeding complications for patients taking antithrombotics is lacking.

Objectives
The study aimed to investigate if perioperative complications were more common in patients with IC/BPS receiving antithrombotic therapy after BH.

Study design
We retrospectively reviewed patients with IC/BPS who underwent hydrodistention during January 2010 and May 2021. Patients with and without antithrombotic drugs were identified and grouped, and their medical records were reviewed. Perioperative data and symptom scores were assessed. The rates of complications in the 2 groups were recorded at 3 months and at the last visit postoperatively.

Results
A total of 387 patients were eventually included. Among them, 29 (7.5%) patients were receiving systemic antithrombotic therapy and 358 (92.5%) were not. Compared with the non-antithrombotic group, patients receiving antithrombotic therapy demonstrated a longer hospital stay (P = 0.033) and a longer catheterization time (P = 0.034). Moreover, the patients with antithrombotic drugs had increased odds of bladder tamponade (odds ratio, 6.76; P = 0.019) and urinary retention (odds ratio, 5.79; P = 0.033) both 3 months postoperatively and last follow-up, but this is not statistically different between patients with and without Hunner lesions. No thromboembolic events were identified during the study period.

Conclusions
Although a small number of patients with IC/BPS needed anticoagulants, longer hospital stays, longer catheterization time, and increased odds of bladder tamponade and urinary retention were observed in patients receiving antithrombotic therapy. Still, a comprehensive management scheme to balance bleeding complications and antithrombotic agents is needed for individuals.
On quantum computing and geometry optimization
Authors: Malik Ashar J. , Verma Chandra S. 
Published: March 2023

AbstractQuantum computers have demonstrated advantage in tackling problems considered hard for classical computers and hold promise for tackling complex problems in molecular mechanics such as mapping the conformational landscapes of biomolecules. This work attempts to explore a few ways in which classical data, relating to the Cartesian space representation of biomolecules, can be encoded for interaction with empirical quantum circuits not demonstrating quantum advantage. Using the quantum circuit in a variational arrangement together with a classical optimizer, this work deals with the optimization of spatial geometries with potential application to molecular assemblies. Additionally this work uses quantum machine learning for protein side-chain rotamer classification and uses an empirical quantum circuit for random state generation for Monte Carlo simulation for side-chain conformation sampling. Altogether, this novel work suggests ways of bridging the gap between conventional problems in life sciences and how potential solutions can be obtained using quantum computers. It is hoped that this work will provide the necessary impetus for wide-scale adoption of quantum computing in life sciences.
Highly Parallel Tissue Grafting for Combinatorial In Vivo Screening
Authors: O’Connor Colleen E. , Neufeld Anna , Fortin Chelsea L. , Johansson Fredrik , Mene Jonathan , Saxton Sarah H. , Simmonds Susana P. , Kopyeva Irina , Gregorio Nicole E. , DeForest Cole A. , Witten Daniela M. , Stevens Kelly R. 
Published: March 2023

AbstractMaterial- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature ofin vivoimplantation experiments. We introduce a ‘plug and play’in vivoscreening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelizedin vivoscreening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can “rescue” vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.
COMT inhibitor tolcapone represses the migration and invasion of trophoblast and results in preeclampsia-like phenotypes in mice with the modulation of EMT signaling
Authors: Chen Lu , Li Yuexia , Pang Menglan , Jie Qiuling , Sun Fei , Huang Liping , Ma Yanlin , Wu Fei , Yue Xiaojing 
Published: March 2023

AbstractPregnancy in young-onset Parkinson’s disease (YOPD) is rare; however, medication for this condition is critical for maternal and fetal health. Tolcapone is an effective antiparkinsonian drug. However, its safety studies on mothers and fetuses are limited. In this study, we aimed to investigate the effects of tolcapone on the mother and the developing fetus during different stages of gestation. Tolcapone was administered to pregnant mice at a dose of 60 (H-Tol) or 30 mg/kg/day (L-Tol) during early or mid-gestation. We observed that tolcapone administration during early gestation causes abortion and delays fetal development in a dose-dependent manner. During mid-gestation tolcapone barely caused embryo lethality; however, the mice developed preeclampsia-like phenotypes, including maternal hypertension, proteinuria, and fetal growth restriction. Histomorphological analysis of placentas from tolcapone treated mice revealed abnormalities in the trophoblast layer and the impaired trophoblast invasion in the decidua. Mechanistically, we revealed that tolcapone inhibits the invasion and migration of trophoblastsin vitro, with changes in the protein expression of Snail, Twist, and E-cadherin. In conclusion, tolcapone caused embryo lethality and growth restriction during early gestation, whereas it caused preeclampsia-like phenotypes in mice with defective trophoblast invasion in mid-gestation. Collectively, our study provides novel insights into the effects of tolcapone on pregnancy.
Integrative proteomics and transcriptomics of human T-cells reveals temporal metabolic reprogramming following TCR-induced activation
Authors: Weerakoon Harshi , Mohamed Ahmed , Wong Yide , Senadheera Bhagya , Haigh Oscar , Watkins Thomas S. , Kazakoff Stephen , Mukhopadhyay Pamela , Mulvenna Jason , Miles John J. , Hill Michelle M. , Lepletier Ailin 
Published: March 2023

AbstractT-cells are critical components of the adaptive immune system. Upon activation, they acquire effector functions through a complex interplay between mRNA transcripts and proteins, the landscape of which remains to be fully elucidated. In this resource article, we present an integrative temporal proteomic and transcriptomic analysis of primary human CD4+and CD8+T-cells followingex vivoactivation with anti-CD3/CD28 Dynabeads. Our data reveal a time-dependent dissociation between the T-cell transcriptome and proteome during activation. A transient downregulation of GLUT1, the central glucose transporter in T-cells, marked the onset of reprogramming in both CD4+and CD8+T-cells. At late activation, CD4+T-cells upregulated enzymes associated with degradation of fatty acids while CD8+T-cells preferentially upregulated enzymes in the metabolism of cofactors and vitamins. Surprisingly, we found that activated CD4+and CD8+T-cells became transcriptionally more divergent at the same time their proteome became more similar. In addition to the metabolic reprogramming highlighted in our analysis, this dataset provides a public resource for understanding temporal molecular changes governing the acquisition of effector functions by T-cells.
ENLIGHT Consensus Checklist and Guidelines for reporting laboratory studies on the non-visual effects of light in humans
Authors: Spitschan Manuel , Kervezee Laura , Lok Renske , McGlashan Elise , Najjar Raymond P. ,   the ENLIGHT Consortium
Published: March 2023

AbstractBeyond vision, light has wide-reaching effects on human health and well-being. However, there is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed at developing a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology. To this end, a four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted. Across these four rounds, an initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n=60). Nine of these items were determined to be necessary to report regardless of the specific research question or context. A description of each item was provided in the accompanying guidelines. Most participants (92%) reported being satisfied or very satisfied with the consensus process, checklist, and guidelines. The ENLIGHT Checklist and Guidelines are the first consensus-based guidelines for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist and guidelines will enhance the impact of light-based research by ensuring comprehensive documentation and reproducibility and enabling data aggregation across studies.
Relating Polar Bears Killed, Human Presence, and Ice Conditions in Svalbard 1987 – 2019
Authors: Vongraven D. , Amstrup S.C. , McDonald T.L. , Mitchell J. , Yoccoz N.G. 
Published: March 2023

ABSTRACTConflicts between humans and polar bears have been predicted to increase as polar bear prime habitat, sea ice, is decreasing. In Svalbard, a strong protection and strict control schemes have secured near complete records of bears killed and found dead since 1987. We analyzed the trend in the number of kills and related this to human visitation to the island. We found a slight decrease in the number of kills in the period 1987-2019, and a decrease in per capita number of kills when monthly kills were compared to the monthly number of visitors disembarking in the main settlement. We then used a discrete choice resource selection model to assess whether polar bear kill events are related to attributes of the kill sites and environmental conditions at the time. We divided Svalbard in four sectors, North, East, South, and West, and monthly average ice cover was calculated in 25-km rings around Svalbard, rings that were further delineated by the four sectors. We found that the odds of a kill was greater along the shoreline, and that the odds would be reduced by 50% when moving only 900 m from the shoreline when all sectors were included. Distance from other covariates like settlements, trapper’s cabins, and landing sites for tourists did for the most part not have a significant impact on the odds of a kill. Sectorwise, ice cover had no significant impact on the odds for a kill. The decreasing trend in kills of polar bears might partly be explained by the success of strict protection and management regimes of Svalbard wilderness.
A 3D-printed flow-cell for on-grid purification of electron microscopy samples directly from lysate
Authors: Ramlaul Kailash , Feng Ziyi , Canavan Caoimhe , Natàlia de Garrido Martín , Carreño David , Crone Michael , Jensen Kirsten E. , Li Bing , Barnet Harry , Riglar David T. , Freemont Paul S. , Miller David , Aylett Christopher H. S. 
Published: March 2023

AbstractWhile recent advances in cryo-EM, coupled with single particle analysis, have the potential to allow structure determination in a near-native state from vanishingly few individual particles, this vision has yet to be realised in practise. Requirements for particle numbers that currently far exceed the theoretical lower limits, challenges with the practicalities of achieving high concentrations for difficult-to-produce samples, and inadequate sample-dependent imaging conditions, all result in significant bottlenecks preventing routine structure determination using cryo-EM. Therefore, considerable efforts are being made to circumvent these bottlenecks by developing affinity purification of samples on-grid; at once obviating the need to produce large amounts of protein, as well as more directly controlling the variable, and sample-dependent, process of grid preparation.In this proof-of-concept study, we demonstrate a further practical step towards this paradigm, developing a 3D-printable flow-cell device to allow on-grid affinity purification from raw inputs such as whole cell lysates, using graphene oxide-based affinity grids. Our flow-cell device can be interfaced directly with routinely-used laboratory equipment such as liquid chromatographs, or peristaltic pumps, fitted with standard chromatographic (1/16”) connectors, and can be used to allow binding of samples to affinity grids in a controlled environment prior to the extensive washing required to remove impurities. Furthermore, by designing a device which can be 3D printed and coupled to routinely used laboratory equipment, we hope to increase the accessibility of the techniques presented herein to researchers working towards single-particle macromolecular structures.
SPLASH2 provides ultra-efficient, scalable, and unsupervised discovery on raw sequencing reads
Authors: Kokot Marek , Dehghannasiri Roozbeh , Baharav Tavor , Salzman Julia , Deorowicz Sebastian 
Published: March 2023

AbstractSPLASH is an unsupervised, reference-free, and unifying algorithm that discovers regulated sequence variation through statistical analysis ofk-mer composition, subsuming many application-specific methods. Here, we introduce SPLASH2, a fast, scalable implementation of SPLASH based on an efficientk-mer counting approach. SPLASH2 enables rapid analysis of massive datasets from a wide range of sequencing technologies and biological contexts, delivering unparalleled scale and speed. The SPLASH2 algorithm unveils new biology (without tuning) in single-cell RNA-sequencing data from human muscle cells, as well as bulk RNA-seq from the entire Cancer Cell Line Encyclopedia (CCLE), including substantial unannotated alternative splicing in cancer transcriptome. The same untuned SPLASH2 algorithm recovers the BCR-ABL gene fusion, and detects circRNA sensitively and specifically, underscoring SPLASH2’s unmatched precision and scalability across diverse RNA-seq detection tasks.
Multiple cancer types rapidly escape from multiple MAPK inhibitors to generate mutagenesis-prone subpopulations
Authors: Hoffman Timothy E. , Yang Chen , Nangia Varuna , Ill C. Ryland , Spencer Sabrina L. 
Published: March 2023

AbstractMany cancers harbor pro-proliferative mutations of the mitogen-activated protein kinase (MAPK) pathway and many targeted inhibitors now exist for clinical use, but drug resistance remains a major issue. We recently showed that BRAF-driven melanoma cells treated with BRAF inhibitors can non-genetically adapt to drug within 3-4 days to escape quiescence and resume slow proliferation. Here we show that this phenomenon is not unique to melanomas treated with BRAF inhibitors but rather is widespread across many clinical MAPK inhibitors and cancer types driven by EGFR, KRAS, and BRAF mutations. In all treatment contexts examined, a subset of cells can escape drug-induced quiescence within four days to resume proliferation. These escapee cells broadly experience aberrant DNA replication, accumulate DNA lesions, spend longer in G2-M cell cycle phases, and mount an ATR-dependent stress response. We further identify the Fanconi anemia (FA) DNA repair pathway as critical for successful mitotic completion in escapees. Long-term cultures, patient samples, and clinical data demonstrate a broad dependency on ATR- and FA-mediated stress tolerance. Together, these results highlight the pervasiveness with which MAPK-mutant cancers are able to rapidly escape drug and the importance of suppressing early stress tolerance pathways to potentially achieve more durable clinical responses to targeted MAPK pathway inhibitors.
Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging
Authors: Cheng Lingling , De Chayan , Li Jieru , Pertsinidis Alexandros 
Published: March 2023

AbstractHow distal enhancers physically control promoters over large genomic distances, to enable cell-type specific gene expression, remains obscure. Using single-gene super-resolution imaging and acute targeted perturbations, we define physical parameters of enhancer-promoter communication and elucidate processes that underlie target gene activation. Productive enhancer-promoter encounters happen at 3D distances δ200 nm - a spatial scale corresponding to unexpected enhancer-associated clusters of general transcription factor (GTF) components of the Pol II machinery. Distal activation is achieved by increasing transcriptional bursting frequency, a process facilitated by embedding a promoter into such GTF clusters and by accelerating an underlying multi-step cascade comprising early phases in the Pol II transcription cycle. These findings help clarify molecular/biochemical signals involved in long-range activation and their means of transmission from enhancer to promoter.
Testing for the fitness benefits of natural transformation during community-embedded evolution
Authors: Winter Macaulay , Harms Klaus , Johnsen Pål Jarle , Buckling Angus , Vos Michiel 
Published: March 2023

AbstractNatural transformation is a process where bacteria actively take up DNA from the environment and recombine it into their genome or reconvert it into extra-chromosomal genetic elements. The evolutionary benefits of transformation are still under debate. One main explanation is that foreign allele and gene uptake facilitates natural selection by increasing genetic variation, analogous to meiotic sex. However, previous experimental evolution studies comparing fitness gains of evolved transforming- and isogenic non-transforming strains have yielded mixed support for the “sex hypothesis.” Previous studies testing the sex hypothesis for natural transformation have largely ignored species interactions, which theory predicts provide conditions favourable to sex. To test for the adaptive benefits of bacterial transformation, the naturally transformable wildtypeAcinetobacter baylyiand a transformation-deficient ΔcomAmutant were evolved for five weeks. To provide strong and potentially fluctuating selection,A. baylyiwas embedded in a community of five other bacterial species. DNA from a pool of differentAcinetobacterstrains was provided as a substrate for transformation. No effect of transformation ability on the fitness of evolved populations was found, with fitness increasing non-significantly in most treatments. Populations showed fitness improvement in their respective environments, with no apparent costs of adaptation to competing species. Despite the absence of fitness effects of transformation, wildtype populations evolved variable transformation frequencies that were slightly greater than their ancestor which potentially could be caused by genetic drift.
Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model
Authors: Mao Xiaotian , Larsen Sabina Birgitte , Zachariassen Line Sidsel Fisker , Brunse Anders , Adamberg Signe , Castro Mejia Josue Leonardo , Larsen Frej , Adamberg Kaarel , Nielsen Dennis Sandris , Hansen Axel Kornerup , Hansen Camilla Hartmann Friis , Rasmussen Torben Sølbeck 
Published: March 2023

AbstractMetabolic syndrome encompasses amongst other conditions like obesity, type-2 diabetes, and metabolic dysfunction associated fatty liver disease (MAFLD), which are all associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM. FMT is generally safe, but motivated by case reports, accidental transfer of pathogenic bacteria remains a concern. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred and FVT from lean male donors has shown promise in alleviating the metabolic effects of a high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, we here apply recently developed modification methodologies to inactivate or remove the eukaryotic viral component of FVT while maintaining an active enteric bacteriophage community. Modified FVTs were compared with unmodified FVT and saline in an animal model of diet-induced obesity using male C57BL/6N mice. In contrast to the obese control group, mice administered a modified FVT, nearly depleted from eukaryotic viruses (0.1%), exhibited enhanced blood glucose clearance, although without a concurrent reduction in weight gain. The unmodified FVT improved liver pathology and reduced the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggested that bacteriophage-mediated GM modulation had influenced these outcomes. When optimized, this may pave the way for developing safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.
Repurposing the dark genome. II - Reverse Proteins
Authors: Nayak Sarangadhar , Dhar Pawan K. 
Published: March 2023

AbstractBased on the expression blueprint encoded in the genome, three groups of sequences have been identified – protein encoding, RNA encoding, and non-expressing. We asked: Why did nature choose a particular DNA sequence for expression? Did she sample every possibility, approving some for RNA synthesis, some for protein synthesis, and retiring/ignoring the rest. If evolution randomly selected sequences for metabolic trials, how much non-utilized (not-expressing) and under-utilized (only RNA encoding) information is currently available for innovations? These questions lead us to experimentally synthesizing functional proteins from intergenic sequences of E.coli (Dhar et al 2009). The current work is an extension of this original report and takes into consideration natural protein-coding sequences ‘read backward’ to generate a new possibility. Reverse proteins are full-length ‘translation equivalents’ of the existing protein-coding genes read in the -1 frame. The structural, functional and interaction predictions of reverse proteins inE.coli, S.cerevisiaeandD.melanogaster, open up a new opportunity of producing ‘first-in-the-class’ proteins towards functional endpoints. This study points to a large untapped genomic space from the fundamental biology and applications perspectives.