bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of HER2 targeted 64Cu-DOTA-tagged PET imaging in gastric cancer patients
Authors: Hernandez Matthew C. , Yazaki Paul , Mortimer Joanne E. , Yamauchi Dave , Poku Erasmus , Park Jinha , Frankel Paul , Kim Joseph , Colcher David M. , Wong Jeffrey , Fong Yuman , Shively John , Woo Yanghee 
Published: October 2023

Objective
Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients.

Methods
We conducted a single-arm phase II pilot study exploring the feasibility of 64Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45 mg of cold trastuzumab followed by 5 mg of 64Cu-DOTA-trastuzumab. PET-CT scans were performed 24–48 h post radiotracer injection and compared to standard staging CT scans.

Results
We observed limited toxicity following 64Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis.

Conclusion
Despite the potential of 64Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5 mg dose of this radiotracer injected 24–48 h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.
Evidence-based guideline on chronic postsurgical pain management in adult patients in resource-restricted setting, 2023: systematic review and guideline
Authors: Milkias Mesay , Mekonnen Semagn , Ahmed Siraj , Getachew Hailemariam , Adamu Yayeh , Mola Simeneh , Gugsa Tesfaye 
Published: October 2023

Background:
Chronic postsurgical pain (CPSP) after tissue trauma is frequent and may have a long-lasting impact on the functioning and quality of life. The development of CPSP increases the burden on both the patient and the community. This review aims to systematically review articles and, lastly, pull an evidence-based guideline for CPSP management in adult patients in resource-limited areas.

Methodology:
The review was reported based on preferred reporting items for the systemic review and meta-analysis (PRISMA) protocol. A literature search was conducted from the Cochrane, PubMed/Medline, and Google Scholar databases, and other gray literature from 2010 to 2022. The conclusion was made based on the level of evidence.

Results:
A total of 3521 articles were identified through the database by searching strategies. Finally, by filtering duplicates unrelated to the topics, 22 articles (9 meta-analyses and systematic reviews, 12 systematic reviews, and one cohort study) were selected on the management of CPSP in adult patients. Filtering was made based on the intervention, outcome data of the population, and methodological quality.

Conclusion:
Given the complexity and multidimensional nature of chronic postsurgical pain, effective assessment, and management require a comprehensive, multiaxial approach. Adequate preoperative preparation and counseling, potential risk identification and optimization, and use of a multimodal approach, and noninvasive surgical techniques are crucial in reducing the development of chronic postsurgical pain.
Kairos infersin situhorizontal gene transfer in longitudinally sampled microbiomes through microdiversity-aware sequence analysis
Authors: Brown Connor L. , Cheung Yat Fei , Song Haoqiu , Snead Delaney , Vikesland Peter , Pruden Amy , Zhang Liqing 
Published: October 2023

AbstractHorizontal gene transfer (HGT) occurring within microbiomes is linked to complex environmental and ecological dynamics that are challenging to replicate in controlled settings. Consequently, most extant studies of microbiome HGT are either simplistic experimental settings with tenuous relevance to real microbiomes or correlative studies that assume that HGT potential is a function of the relative abundance of mobile genetic elements (MGEs), the vehicles of HGT. Here we introduce Kairos as a bioinformatic tool deployed in nextflow for detecting HGT events “in situ,” i.e., within a microbiome, through analysis of time-series metagenomic sequencing data. Thein-situframework proposed here leverages available metagenomic data from a longitudinally sampled microbiome to assess whether the chronological occurrence of potential donors, recipients, and putatively transferred regions could plausibly have arisen due to HGT over a range of defined time periods. The centerpiece of the Kairos workflow is a novel competitive read alignment method that enables discernment of even very similar genomic sequences, such as those produced by MGE-associated recombination. A key advantage of Kairos is its reliance on assemblies rather than metagenome assembled genomes (MAGs), which avoids systematic exclusion of accessory genes associated with the binning process. In an example test-case of real world data, use of assemblies directly produced a 264-fold increase in the number of antibiotic resistance genes included in the analysis of HGT compared to analysis of MAGs with MetaCHIP. Further,in silicoevaluation of contig taxonomy was performed to assess the accuracy of classification for both chromosomally- and MGE-derived sequences, indicating a high degree of accuracy even for conjugative plasmids up to the level of class or order. Thus, Kairos enables the analysis of very recent HGT events, making it suitable for studying rapid prokaryotic adaptation in environmental systems without disturbing the ornate ecological dynamics associated with microbiomes. Current versions of the Kairos workflow are available here:https://github.com/clb21565/kairos.
Modular vector assembly enables rapid assessment of emerging CRISPR technologies
Authors: McGee Abby V. , Liu Yanjing V. , Griffith Audrey L. , Szegletes Zsofia M. , Wen Bronte , Kraus Carolyn , Miller Nathan W. , Steger Ryan J. , Velasco Berta Escude , Bosch Justin A. , Zirin Jonathan D. , Viswanatha Raghuvir , Sontheimer Erik J. , Goodale Amy , Greene Matthew A. , Green Thomas M. , Doench John G. 
Published: October 2023

ABSTRACTThe diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly-described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a modular set of CRISPR cassettes and delivery technologies, along with a web portal, resulting in a combinatorial platform that enables scalable vector assembly within days. We further demonstrate that multiple CRISPR technologies can be assessed in parallel in a pooled screening format using this resource, enabling the rapid optimization of both novel technologies and cellular models. These results establish Fragmid as a robust system for the rapid design of CRISPR vectors, and we anticipate that this assembly approach will be broadly useful for systematic development, comparison, and dissemination of CRISPR technologies.
Exploring the Accuracy of Differentiation-Based Regressive Models in Disease Forecasting
Authors: Karimirad Rojina 
Published: October 2023

ABSTRACTPredictive models have been able to foresee outbreaks of mosquito-borne diseases such as malaria and map Ebola outbreaks1. This has allowed health organizations to plan the amount of resources and the number of healthcare workers needed more effectively, on top of finding out other useful data such as the locations most vulnerable to the disease and the demographics most affected. It can therefore be assumed that predictive analytics can reduce the amount of economic and non-economic burden caused by other epidemics as well, with COVID-19 being an obvious example.
Altered PBP4 and GdpP functions synergistically mediate MRSA-like high-level, broad-spectrum β-lactam resistance inStaphylococcus aureus
Authors: Lai Li-Yin , Satishkumar Nidhi , Cardozo Sasha , Hemmadi Vijay , Marques Leonor B. , Huang Liusheng , Filipe Sergio R. , Pinho Mariana G. , Chambers Henry F. , Chatterjee Som S. 
Published: October 2023

AbstractInfections caused byStaphylococcus aureusare a leading cause of mortality worldwide.S. aureusinfections caused by Methicillin-ResistantStaphylococcus aureus(MRSA) are particularly difficult to treat due to their resistance to Next Generation β-lactams (NGB) such as Methicillin, Nafcillin, Oxacillin etc. Resistance to NGBs, which is alternatively known as broad-spectrum β- lactam resistance is classically mediated by PBP2a, a Penicillin-Binding Protein encoded bymecA(ormecC) in MRSA. Thus, presence ofmecgenes amongS. aureusserves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated,mecAdeficientS. aureusstrains can also exhibit NGB resistance. These strains, which are collectively termed as Methicillin-Resistant Lackingmec(MRLM) are currently being identified in increasing numbers among natural resistant isolates ofS. aureus. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance towards NGBs at levels comparable to that of MRSAs. Our study, provides a fresh new perspective about alternative mechanisms of NGBs resistance, challenging our current overall understanding of high-level, broad-spectrum β-lactam resistance inS. aureus. It thus suggests reconsideration of the current approach towards diagnosis and treatment of β-lactam resistantS. aureusinfections.
Apple and banana fruits produce anteiso- and iso-branched-chain esters from newly synthesized precursors
Authors: Engelgau Philip , Wendakoon Sumithra K. , DuBois Aubrey , Mayhew Emily J. , Beaudry Randolph 
Published: October 2023

AbstractInhibitors of acetohydroxyacid synthase, the common enzyme of branched-chain amino acid biosynthesis, were applied to ripening apple (Malus×domesticaBorkh.), banana (Musaspp.), and flowering quince (Chaenomeles×superba) fruits to discern the contribution of newly synthesized precursors to branched-chain ester formation. After treatment, anteiso- and iso-branched-chain volatiles (i.e., those related to isoleucine, and valine and leucine, respectively) were observed to universally decrease in content. Fruits recovered production following exogenous feeding of branched-chain ⍺-ketoacids. Furthermore, apple and banana fruits were capable of metabolizing all three branched-chain ⍺-ketoacids to esters. Among free amino acids, only the branched-chain amino acids with correspondingly reduced branched-chain esters had a lesser concentration following treatment with inhibitor. Our results ultimately reject the hypothesis that anteiso- and iso-branched-chain esters are derived from preexisting amino acids and instead support the hypothesis that these esters are the product ofde novoprecursor biosynthesis. The novel use of these inhibitors also allowed for further investigation of branched-chain volatile biosynthesis, the citramalate synthase pathway, and the importance of precursor availability in fruits. Notably, in ‘Valery’ banana fruit, ethyl acetate and butyl acetate were found to be dependent on acetohydroxyacid synthase activity for production whereas 1-methylbutyl acetate and 1-methylbutyl butanoate (sec-branched-chain esters) were not. Inhibitor usage on apples also allowed for a sensory study that found that humans can discern the absence of 2-methylbutyl and 2-methylbutanoate esters in apple fruit. Additionally, a population genetics analysis found that there is selection pressure against apples that lack these esters.
Insights into assembly of constitutive filament-forming proteins of novel fold through domain dissection and EGFP insertion-based screen: A case study ofSpiroplasmaFibril
Authors: Bapat Mrinmayee , Harne Shrikant , Kashyap Rajnandani , Gayathri Pananghat 
Published: October 2023

AbstractSpiroplasmais a cell-wall less, helical bacterium possessing a cytoskeletal ribbon consisting Fibril and 5 MreB paralogs. In absence of any information regarding the filament interface of Fibril, a cytoskeleton protein of novel fold, multiple short constructs of Fibril were designed to identify minimal domains required for polymerization. Purification trials of these short constructs resulted in insoluble protein products. In a parallel approach, we incorporated EGFP at the loop regions aimed to hinder polymerization and obtain non-polymerising constructs. We were able to identify probable interfilament/intrafilament interface residues based on the fluorescence screen. We show that EGFP insertions at many of the positions are tolerated as Fibril filaments were readily observed for these constructs in transmission electron microscopy. Both the approaches suggest that Fibril requires N and C-terminal domains for its polymerization. Earlier studies have shown that FibrilWTinteracts with MreB5. Our Fibril-EGFP constructs and MreB5 showed interaction similar to the wild-type. Co-sedimentation assay and visualization of Fibril-EGFP proteins proves that the fluorescent constructs are folded and functional and possess structural and biochemical properties similar to the wild type protein.
PhysiMeSS - A New PhysiCell Addon for Extracellular Matrix Modelling
Authors: Noël Vincent , Ruscone Marco , Shuttleworth Robyn , Macnamara Cicely K. 
Published: October 2023

AbstractThe extracellular matrix is a complex assembly of macro-molecules, such as collagen fibres, which provides structural support for surrounding cells. In the context of cancer metastasis, it represents a barrier for the cells, that the migrating cells needs to degrade in order to leave the primary tumor and invade further tissues. Agent-based frameworks, such as PhysiCell, are often use to represent the spatial dynamics of tumor evolution. However, typically they only implement cells as agents, which are represented by either a circle (2D) or a sphere (3D). In order to accurately represent the extracellular matrix as a network of fibres, we require a new type of agent represented by a segment (2D) or a cylinder (3D).In this article, we present PhysiMeSS, an addon of PhysiCell, which introduces a new type of agent to describe fibres, and their physical interactions with cells and other fibres. PhysiMeSS implementation is publicly available athttps://github.com/PhysiMeSS/PhysiMeSS, as well as in the official Physi-Cell repository. We also provide simple examples to describe the extended possibilities of this new framework. We hope that this tool will serve to tackle important biological questions such as diseases linked to dis-regulation of the extracellular matrix, or the processes leading to cancer metastasis.
SCD1 and monounsaturated lipids are required for autophagy and survival of adipocytes
Authors: Mori Hiroyuki , Peterson Sydney K. , Simmermon Rachel , Overmyer Katherine A. , Nishii Akira , Paulsson Emma , Li Ziru , Jen Annie , Uranga Romina M. , Maung Jessica , Yacawych Warren T. , Lewis Kenneth T. , Schill Rebecca L. , Hetrick Taryn , Seino Ryo , Inoki Ken , Coon Joshua J. , MacDougald Ormond A. 
Published: October 2023

ABSTRACTExposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (SCD1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. In this study, we employedScd1knockout cells and mouse models, along with pharmacological SCD1 inhibition, to investigate further the roles of SCD1 in adipocytes. Our study reveals that production of monounsaturated lipids by SCD1 is necessary for fusion of autophagosomes to lysosomes and that with a SCD1-deficiency, autophagosomes accumulate. In addition, SCD1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of SCD1-deficient adipocytes. Taken together, our results demonstrate thatin vitroinhibition of SCD1 in adipocytes leads to autophagy-dependent cell death, andin vivodepletion leads to loss of bone marrow adipocytes.
Selection leads to false inferences of introgression using popular methods
Authors: Smith Megan L. , Hahn Matthew W. 
Published: October 2023

AbstractDetecting introgression between closely related populations or species is a fundamental objective in evolutionary biology. Existing methods for detecting migration and inferring migration rates from population genetic data often assume a neutral model of evolution. Growing evidence of the pervasive impact of selection on large portions of the genome across diverse taxa suggests that this assumption is unrealistic in most empirical systems. Further, ignoring selection has previously been shown to negatively impact demographic inferences (e.g., of population size histories). However, the impacts of biologically realistic selection on inferences of migration remain poorly explored. Here, we simulate data under models of background selection, selective sweeps, balancing selection, and adaptive introgression. We show that ignoring selection sometimes leads to false inferences of migration in popularly used methods that rely on the site frequency spectrum (SFS). Specifically, balancing selection and some models of background selection result in the rejection of isolation-only models in favor of isolation-with-migration models and lead to elevated estimates of migration rates. BPP, a method that analyzes sequence data directly, showed false positives for all conditions at recent divergence times, but balancing selection also led to false positives at medium divergence times. Our results suggest that such methods may be unreliable in some empirical systems, such that new methods that are robust to selection need to be developed.Article SummaryDetecting migration between closely related populations is a central objective in many evolutionary biology studies. However, popular methods for detecting migration assume a simplified model of evolution. Here, we evaluate the impacts of biologically realistic natural selection, recombination, and mutation on three methods for detecting migration. We find that biological complexity leads to false inferences of migration, suggesting that results should be interpreted with caution and that new methods are needed to make robust inferences of migration across empirical systems.
Prefrontal suppression in short-video viewing: unraveling the neural correlates of self-control
Authors: Su Conghui , Teng Binyu , Zhou Hui , Geng Fengji , Hu Yuzheng 
Published: October 2023

AbstractThe recent surge in short-video application usage has raised concerns about potential mental health risks. Using a novel video-watching task, we investigated the neuropsychological mechanisms underlying self-control during short-video viewing from a dual-system perspective. Results revealed watching preferred videos significantly activated the amygdala (System I) and deactivated the control regions (System II), with individuals with lower trait self-control being suppressed more. Dynamic causal modelling revealed the amygdala inhibited control regions during preferred viewing, while control regions downregulated the amygdala during less-preferred viewing. The control regions also demonstrated enhanced activation during cognitive control and inner-state monitoring tasks, with the latter correlating with trait self-control. These findings suggest preference-based video-watching suppresses prefrontal areas that represent rules and support self-awareness, enabling bottom-up limbic processes to dominate attention. This study provides insights into the neuropsychological impacts of short-video applications use, informing policies and interventions to promote healthier technology use and mitigate potential adverse effects.
Wastewater Tiling Amplicon Sequencing Reveals Longitudinal Dynamics of SARS-CoV-2 Variants Prevalence in the Community
Authors: Wang Yu , Ni Gaofeng , Tian Wei , Wang Haofei , Li Jiaying , Thai Phong , Choi Phil M. , Jackson Greg , Hu Shihu , Yang Bicheng , Guo Jianhua 
Published: October 2023

AbstractSARS-CoV-2 continues to evolve, while the decline in clinical sequencing efforts hampers public health sectors to prepare for the menace of ongoing variant emergence and future COVID-19 surges.1Wastewater-based epidemiology (WBE) has been proposed to provide complementary insights on the variants being transmitted in communities.2However, limited research has been dedicated to the use sequencing methods for tracking disease prevalence and variant dynamics in wastewater, particularly on a large scale. Here, we employed a tiling amplicon sequencing to track the dynamics of variant of concern (VOC) in wastewater collected from Queensland, Australia from 2020 to 2022. RNA concentrations in wastewater measured by ATOPlex showed a stronger correlation and greater consistency with the number of daily new cases than a PCR-based method. The VOC dynamics observed in wastewater were largely in line with clinical reports. These findings support that WBE and sensitive sequencing methods can serve as a long-term approach for disease surveillance, thus aiding in disease outbreak prevention, control, and management.
Autism diagnosis experience and parental stress among Portuguese parents
Authors: Kulari Genta , Sarantakos Cordeiro Giulia Francisca 
Published: October 2023

Purpose
This study aims to examine the impact that diagnostic factors such as duration of diagnostic period, number of professionals consulted and perceived social support have on parental stress during the diagnostic process of autism spectrum disorder (ASD).

Design/methodology/approach
Forty parents of 2–18 year-old children/adolescents with a formal ASD diagnosis recruited from five specialized private clinics in Lisbon completed a survey which included diagnostic questionnaire, parental stress scale and social support scale from April to December 2022.

Findings
Data analysis indicated that the mean age of the diagnosis was 5.6 years with a delay of 3.95 years from first concern until final diagnosis. On average, parents consulted a mean of 3.62 professionals. Other findings indicated that as age of parents increased, levels of parental stress decreased. Parents with higher levels of social support had lower levels of parental stress. Furthermore, higher age of child at first concern predicted higher affective social support.

Originality/value
This study reflects on the experience of obtaining the ASD diagnosis in Portugal, raising awareness on the importance of providing early detection and social support for distressed parents.