bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction: A randomized non-inferiority trial
Authors: Zhao Xingshan , Zhu Yidan , Zhang Zheng , Tao Guizhou , Xu Haiyan , Cheng Guanchang , Gao Wen , Ma Liping , Qi Liping , Yan Xiaoyan , Wang Haibo , Xia Qingde , Yang Yuwang , Li Wanke , Rong Juwen , Wang Limei , Ding Yutian , Guo Qiang , Dang Wanjun , Yao Chen , Yang Qin , Gao Runlin , Wu Yangfeng , Qiao Shubin 
Published: June 2023

Abstract

Background:
A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.

Methods:
In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.

Results:
From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA (n = 384) or rt-PA (n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups.

Conclusion:
rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.

Trial registration:

www.ClinicalTrials.gov (No. NCT02835534).
The genetic background of female reproductive disorders: a systematic review
Authors: Doulgeraki Triada , Papageorgopoulou Maria , Iliodromiti Stamatina 
Published: June 2023

Purpose of review
Reproductive function is the interplay between environmental factors and the genetic footprint of each individual. The development in genetic analysis has strengthened its role in the investigation of female reproductive disorders, potential treatment options and provision of personalized care. Despite the increasing requirement of genetic testing, the evidence of the gene–disease relationships (GDR) is limited. We performed a systematic review exploring the associations between the most frequent female reproductive endocrine disorders associated with subfertility [including polycystic ovaries syndrome (PCOS), premature ovarian failure (POI) and hypogonadotropic hypogonadism] and their genetic background in order to summarize current knowledge.

Methods
A systematic review of relevant literature in accordance with PRISMA guidelines was conducted until July 2022. Data sources that were used are PubMed and Embase.

Recent findings
A total of 55 studies were included from the 614 articles identified in the original search. We identified 384 genes associated with one or more of the included female reproductive disorders. The highest number of genes was found to be associated with POI (N = 209), followed by hypogonadotropic hypogonadism (N = 88) and PCOS (N = 87). Four genes, including FSHR, LHβ, LEPR and SF1 were associated with multiple reproductive disorders implying common pathways in the development of those diseases.

Summary
We provide an up-to-date summary of the currently known genes that are associated with three female reproductive disorders (PCOS, POI and hypogonadotropic hypogonadism). The role of genetic analysis in the field of impaired female reproduction may have a role in the diagnosis of female reproductive disorders and personalized patient care.
Pelvic abscess – to drain or not to drain?
Authors: Strong Sophie Michelle , Lazanakis Stylianos Michail , Ball Elizabeth 
Published: June 2023

Purpose of review
Pelvic abscess is a common gynaecological condition, particularly during and after the Covid-19 pandemic, possibly resulting from obstacles to accessing care during this time. To date, no consensus guideline on management exists with a lack of applicable randomized controlled trials (RCTs) comparing medical management with antibiotics alone, image-guided drainage and surgical management, despite this being a potentially life-threatening condition.

Recent findings
We present the current literature assessing risks, which contribute to failure of medical therapy, predictive models to guide management and reports of long-term sequelae. Consideration for early laparoscopic or image-guided drainage should be given to women in whom fertility is a priority, pelvic abscess at least 7 cm, white blood cell count on admission more than 16 x 1000/μl, bilateral pelvic abscess, intrauterine device in situ for more than 5.5 years and preexisting endometrioma. Pelvic abscess rupture or severe sepsis should always trigger timely drainage.

Summary
We present the current knowledge on management of pelvic abscesses to help guide clinical practice supported by the most recent evidence. We report the lack of high-quality evidence for many aspects of pelvic abscess treatment and call for well designed large multicentre RCTs to answer the question of which treatment yields the best outcomes.
Research Progress on the Potential Mechanisms of Acute Kidney Injury and Chronic Kidney Disease Induced by Proton Pump Inhibitors
Authors: Song Zhiyong , Gong Xuezhong 
Published: June 2023

ABSTRACT
Proton pump inhibitors (PPIs) are acid-suppressing medications widely used in peptic ulcers; however, their widespread use has led to many adverse renal events. Among these events, the most common form of acute kidney injury (AKI) is acute interstitial nephritis (AIN), which is the clinical manifestation. Several clinical trials and cohort studies have shown a significant relationship between PPIs and AKI induction; however, the pathogenesis of PPIs leading to AKI is unclear. In this paper, we reviewed the potential mechanisms by which PPIs cause AKI and proposed new conjectures. We considered that PPIs led to the development of AKI through a combination of mechanisms. By searching and reviewing PubMed and Embase, a total of 29 studies were finally included and reviewed, and the findings suggested that the mechanisms by which PPIs induce AKI are mainly related to oxidative stress, immune response, inflammatory response, mitochondrial damage, calcium overload, and the induction of cellular necrosis. In addition, tubular cell necrosis can cause tubulointerstitial fibrosis and progressive renal unit loss. Long-term follow-up observations also suggested that PPIs can contribute to AKI progression to chronic kidney disease (CKD). Therefore, we will also explore the potential link between PPIs and CKD.
Blessings and barriers: Achieving autonomous practice in Florida
Authors: Stone-Gale Vicky 
Published: June 2023

ABSTRACT
Florida advanced practice registered nurses have worked tirelessly for many years to practice to the fullest extent of their training and education, yet medical associations halted any progress they have tried to make. In the 2020 legislative session, House Bill 607, the Direct Care Workers bill was finally passed, allowing nurse practitioners who practice in specific primary care areas to practice autonomously. This still requires many Advanced Practice Registered Nurses in the state to have a collaborative practice agreement. Therefore, there is more work to be done to remove those practice barriers.
Minimal condition repetitions required in rapid serial visual presentation decoding paradigms
Authors: Grootswagers Tijl 
Published: June 2023

AbstractRapid Serial Visual Presentation (RSVP) decoding paradigms allow testing a greater number of conditions than was previously possible within short experimental sessions. However, in these designs individual neural responses may be more susceptible to noise due to responses overlapping with adjacent epochs. This study investigates the minimum number of repetitions required for reliable decoding accuracies in RSVP decoding paradigms. We used previously published EEG data and conducted a standard decoding analysis while varying the number of repetitions used. We found that it is possible to obtain reliable decoding accuracies with only around six repetitions of each condition, which has important implications for research questions that require short experiments, particularly for studying populations who may not be able to tolerate longer or more demanding protocols. These findings highlight the potential benefits of using efficient RSVP decoding designs and conducting short experiments and may have far-reaching impacts in cognitive neuroscience, by providing insights into optimizing data collection methods for diverse populations and experimental protocols.
TPPP Forms Liquid Condensates and Aggregates in Multiple System Atrophy
Authors: Kemal Shahrnaz , Richardson Hunter S. , McAlear Thomas S. , Kopach Andrii , Nowacki Joseph C. , Li Yan , Bechstedt Susanne , Fu Meng-meng 
Published: June 2023

ABSTRACTOligodendrocytes have elaborate arbors of microtubules that extend toward axons and spiral around myelin sheaths. Oligodendrocytes rely on satellite organelles called Golgi outposts to nucleate new microtubules at sites far from the cell body. We now show that the Golgi outpost marker TPPP (tubulin polymerization promoting protein) forms liquid condensates that co-partition with tubulin in order to nucleate microtubules. In oligodendrocytes, TPPP forms either dynamic puncta or aberrant microtubule-associated aggregates. In Multiple System Atrophy (MSA), a sequela of histological events initiates with TPPP aggregation in myelin sheaths and terminates in perinuclear TPPP co-aggregation with alpha-synuclein (aSyn). Finally, recombinant TPPP aggregates are toxic to primary oligodendrocytes. Thus, while the liquid condensate property of TPPP facilitates microtubule nucleation, it also predisposes TPPP to aggregate in disease.
Therapeutic TNF-alpha Delivery After CRISPR Receptor Modulation in the Intervertebral Disc
Authors: Stover Joshua D. , Trone Matthew A. R. , Weston Jacob , Lewis Christian , Levis Hunter , Philippi Matthew , Zeidan Michelle , Lawrence Brandon , Bowles Robby D. 
Published: June 2023

ABSTRACTLow back pain (LBP) ranks among the leading causes of disability worldwide and generates a tremendous socioeconomic cost. Disc degeneration, a leading contributor to LBP, can be characterized by the breakdown of the extracellular matrix of the intervertebral disc (IVD), disc height loss, and inflammation. The inflammatory cytokine TNF-α has multiple pathways and has been implicated as a primary mediator of disc degeneration. We tested our ability to regulate the multiple TNF-α inflammatory signaling pathwaysin vivoutilizing CRISPR receptor modulation to slow the progression of disc degeneration in rats. Sprague-Dawley rats were treated with CRISPRi-based epigenome-editing therapeutics targeting TNFR1 and showed a decrease in behavioral pain in a disc degeneration model. Surprisingly, while treatment with the vectors alone was therapeutic, TNF-α injection itself became therapeutic after TNFR1 modulation. These results suggest direct inflammatory receptor modulation, to harness beneficial inflammatory signaling pathways, as a potent strategy for treating disc degeneration.
Learning structural heterogeneity from cryo-electron sub-tomograms with tomoDRGN
Authors: Powell Barrett M. , Davis Joseph H. 
Published: June 2023

ABSTRACTCryo-electron tomography (cryo-ET) allows one to observe macromolecular complexes in their native, spatially contextualized environment. Tools to visualize such complexes at nanometer resolution via iterative alignment and averaging are well-developed but rely on assumptions of structural homogeneity among the complexes under consideration. Recently developed downstream analysis tools allow for some assessment of macromolecular diversity but have limited capacity to represent highly heterogeneous macromolecules, including those undergoing continuous conformational changes. Here, we extend the highly expressive cryoDRGN deep learning architecture, originally created for cryo-electron microscopy single particle analysis, to sub-tomograms. Our new tool, tomoDRGN, learns a continuous low-dimensional representation of structural heterogeneity in cryo-ET datasets while also learning to reconstruct a large, heterogeneous ensemble of structures supported by the underlying data. Using simulated and experimental data, we describe and benchmark architectural choices within tomoDRGN that are uniquely necessitated and enabled by cryo-ET data. We additionally illustrate tomoDRGN’s efficacy in analyzing an exemplar dataset, using it to reveal extensive structural heterogeneity among ribosomes imagedin situ.
zDB: bacterial comparative genomics made easy
Authors: Marquis Bastian , Pillonel Trestan , Carrara Alessia , Bertelli Claire 
Published: June 2023

ABSTRACTThe analysis and comparison of genomes relies on different tools for tasks such as annotation, orthology prediction and phylogenetic inference. Most tools are specialized for a single task and additional efforts are necessary to integrate and visualize the results. To fill this gap, we developed zDB, an application that integrates an analysis pipeline and a visualization platform. Starting from annotated Genbank files, zDB identifies orthologs and infers a phylogeny for each orthogroup. A species phylogeny is also constructed from shared single-copy orthologs. The results can be enriched with Pfam protein domain prediction, COG and KEGG annotations and Swissprot homologs. The web application allows searching for specific genes or annotations, running Blast queries and comparing genomic regions and whole genomes. The metabolic capacities of organisms can be compared at either the module or pathway levels. Finally, users can run queries to examine the conservation of specific genes or annotations across a chosen subset of genomes and display the results as a list of genes, Venn diagram or heatmaps. Those features will make zDB useful for both bioinformaticians and researchers more accustomed to laboratory research. zDB is perfectly suited to process datasets with tens to hundred of genomes on a desktop machine.IMPORTANCEGenome comparison and analysis rely on many independent tools, leaving to scientists the burden to integrate and visualize their results for interpretation. To alleviate this burden, we have built zDB, a comparative genomics tool that includes both an analysis pipeline and a visualization platform. The analysis pipeline automates gene annotation, orthology prediction and phylogenetic inference, while the visualization platform allows scientists to easily explore the results in a web browser. Among other features, the interface allows users to visually compare whole genomes and targeted regions, assess the conservation of genes or metabolic pathways, perform Blast searches or look for specific annotations. Altogether, this tool will be useful for a broad range of applications in comparative studies between two to hundred genomes. Furthermore, it is designed to allow sharing datasets easily at local or international scale, thereby supporting exploratory analyses for non-bioinformaticians on the genome of their favorite organisms.
Design Automation of Microfluidic Single and Double Emulsion Droplets with Machine Learning
Authors: Lashkaripour Ali , McIntyre David P. , Calhoun Suzanne G.K. , Krauth Karl , Densmore Douglas M. , Fordyce Polly M. 
Published: June 2023

AbstractDroplet microfluidics enables kHz screening of picoliter samples at a fraction of the cost of other high-throughput approaches. However, generating stable droplets with desired characteristics typically requires labor-intensive empirical optimization of device designs and flow conditionsthat limit adoption to specialist labs. Here, we compile the most comprehensive droplet dataset to date and use it to train machine learning models capable of accurately predicting device geometries and flow conditions required to generate stable aqueous-in-oil and oil-in-aqueous single and double emulsions from 15 to 250μm at rates up to 12000 Hz for different fluids commonly used in life sciences. Novel device geometries predicted by our models for as-yet-unseen fluids yield accurate predictions, establishing their generalizability. Finally, we generate an easy-to-use design automation tool that yield droplets within 3μm (< 8%) of the desired diameter, facilitating tailored droplet-based platforms for new applications and accelerating their utility in life sciences.
Absence of electron transfer-associated changes in the time-dependent X-ray free-electron laser structures of the photosynthetic reaction center
Authors: Nishikawa Gai , Sugo Yu , Saito Keisuke , Ishikita Hiroshi 
Published: June 2023

ABSTRACTUsing the X-ray free-electron laser (XFEL) structures of the photosynthetic reaction center fromBlastochloris viridisthat show light-induced time-dependent structural changes [Dods, R.et al. (2021) Nature589, 310-314], we investigated time-dependent changes in the energetics of the electron transfer pathway, considering the entire protein environment of the protein structures and titrating the redox active sites in the presence of all fully equilibrated titratable residues. In the dark and charge-separation intermediate structures, the calculated redox potential (Em) values for the accessory bacteriochlorophyll and bacteriopheophytin in the electron-transfer active branch (BLand HL) are higher than those in the electron-transfer inactive branch (BMand HM). However, the stabilization of the [PLPM]•+HL•–state owing to protein reorganization is not clearly observed in theEm(HL) values in the charge-separated 5-ps ([PLPM]•+HL•–state) structure. Furthermore, the expected chlorin ring deformation upon formation of HL•–(saddling mode) is absent in the HLgeometry of the original 5-ps structure. These findings suggest that there is no clear link between the time-dependent structural changes and the electron transfer events in the XFEL structures.
Characterisation of membrane protein interactions by peptidisc-mediated mass photometry
Authors: Young John William , Pfitzner Emanuel , Kukura Philipp , Robinson Carol V. 
Published: June 2023

ABSTRACTMembrane proteins perform a variety of critical functions in the cell, making many of them primary drug targets. At the same time, their preference for a lipid environment makes them challenging to study using established solution-based methods. Here, we show that peptidiscs, a recently developed membrane mimetic, provide an ideal platform to study membrane proteins and their interactions with mass photometry (MP) in detergent-free conditions. The mass resolution for membrane protein complexes is similar to that achievable with soluble proteins owing to the low carrier heterogeneity. Using two well-characterized bacterial membrane protein complexes - the ABC transporter BtuCD, and the Sec translocon - we show that MP can quantify interactions between peptidisc-reconstituted membrane protein receptors and their soluble protein binding partners. Using the BAM complex, we further show that MP reveals interactions between a membrane protein receptor and a bactericidal antibody. Our results highlight the utility of peptidiscs for membrane protein characterization in detergent-free solution and provide a rapid and powerful platform for quantifying membrane protein interactions.
Sixteen oogenesin genes are dispensable for fertilityWhat is the significance of the dispensability of genes expressed in germ-cell?
Authors: Castille Johan , Thépot Dominique , Fouchécourt Sophie , Passet Bruno , Daniel-Carlier Nathalie , Vilotte Jean-Luc , Monget Philippe 
Published: June 2023

AbstractGene knockout experiments have shown that many genes are dispensable for a given biological function. The Oogenesin/Pramel family contains almost 85 paralogs, about thirty of which are specific to female (as well as male for some of them) germ cells. In this paper, we show that the deletion of a block of around 1Mb containing sixteen paralogous genes of the Oogenesin/Pramel family specific to germ cells, including Oogenesin-2, -3 and -4, has no consequences on fertility or prolificacy in mouse both sexes. The dispensability of these genes is probably due to the compensation by the other germ-cell specific paralogs.
Mapping temperature-sensitive mutations at a genome-scale to engineer growth-switches inE. coli
Authors: Schramm Thorben , Pahl Vanessa , Link Hannes 
Published: June 2023

AbstractTemperature-sensitive (TS) mutants are a unique tool to perturb and engineer cellular systems. Here, we constructed a CRISPR library with 15,120Escherichia colimutants, each with a single amino acid change in one of 346 essential proteins. 1,269 of these mutants showed temperature-sensitive growth in a time-resolved competition assay. We reconstructed 94 TS mutants and measured their metabolism under growth arrest at 42°C using metabolomics. Metabolome changes were strong and mutant-specific, showing that metabolism of non-growingE. coliis perturbation-dependent. For example, 24 TS mutants of metabolic enzymes overproduced the direct substrate-metabolite due to a bottleneck in their associated pathway. A strain with TS homoserine kinase (ThrBF267D) produced homoserine for 24 hours, and production was tunable by temperature. Finally, we used a TS subunit of DNA polymerase III (DnaXL289Q) to decouple growth from arginine overproduction in engineeredE. coli. These results provide a strategy to identify TS mutantsen masseand demonstrate their large potential to produce bacterial metabolites with non-growing cells.