bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interrater and test–retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis
Authors: Brady Sophia M. , Georgopoulos Vasileios , Veldhuijzen van Zanten Jet J.C.S. , Duda Joan L. , Metsios George S. , Kitas George D. , Fenton Sally A.M. , Walsh David A. , McWilliams Daniel F. 
Published: October 2023

AbstractIntroduction:Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions.Objectives:We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test–retest reliability.Methods:The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test–retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups.Results:High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01–0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP.Conclusion:PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.
Implementation of a Stepped Care Program to Address Emotional Recovery Among Traumatic Injury Patients
Authors: Davidson Tatiana M , Espeleta Hannah C , Ridings Leigh E , Witcraft Sara , Bravoco Olivia , Higgins Kristen , Houchins Rachel , Kitchens Debra , Manning Benjamin , Jones Seon , Crookes Bruce , Hanson Rochelle , Ruggiero Kenneth J 
Published: October 2023

Background
Annually, over 600,000 adults served in U.S. trauma centers (≥ 20%) develop posttraumatic stress disorder (PTSD) and/or depression in the first year after injury. American College of Surgeons guidelines include screening and addressing mental health recovery in trauma centers. Yet, many trauma centers do not monitor and address mental health recovery, and it is a priority to learn how to implement evidence-informed mental health programs in trauma centers.

Study Design.
This paper describes our application of the Exploration, Preparation, Implementation, Sustainment 15 model to implement the Trauma Resilience and Recovery Program (TRRP) in three Level I-II trauma centers to address patients' mental health needs. TRRP is a scalable and sustainable stepped model of care – one of the few in the US - that provides early intervention and direct services after traumatic injury.

Results.
Trauma centers are well-positioned to accelerate mental health recovery via early identification, education, screening, and referrals to mental health agencies that provide best-practice care. We found that TRRP was acceptable to our three partnering trauma centers. Engaging patient, provider, and hospital administration stakeholders early in the implementation process enhanced buy-in during the early stages of implementation and promoted sustainability. Active processes to support monitoring, evaluation, and adaptation were critical.

Conclusions.
Our work demonstrates the feasibility of implementing and adapting TRRP, a cost-efficient and sustainable stepped care intervention, in Level I and II trauma centers. Several factors should be carefully considered by trauma centers seeking to integrate behavioral health interventions into their trauma program.
Urban flask measurements of CO2ff and CO to identify emission sources at different site types in Auckland, New Zealand
Authors: Young Hayden A. , Turnbull Jocelyn C. , Keller Elizabeth D. , Domingues Lucas Gatti , Parry-Thompson Jeremy , Hilton Timothy W. , Brailsford Gordon W. , Gray Sally , Moss Rowena C. , Mikaloff-Fletcher Sara 
Published: October 2023

As part of the CarbonWatch-NZ research programme, air samples were collected at 28 sites around Auckland, New Zealand, to determine the atmospheric ratio (RCO) of excess (local enhancement over background) carbon monoxide to fossil CO2(CO2ff). Sites were categorized into seven types (background, forest, industrial, suburban, urban, downwind and motorway) to observeRCOaround Auckland. Motorway flasks observedRCOof 14 ± 1 ppb ppm−1and were used to evaluate trafficRCO. The similarity between suburban (14 ± 1 ppb ppm−1) and trafficRCOsuggests that traffic dominates suburban CO2ff emissions during daytime hours, the period of flask collection. The lower urbanRCO(11 ± 1 ppb ppm−1) suggests that urban CO2ff emissions are comprised of more than just traffic, with contributions from residential, commercial and industrial sources, all with a lowerRCOthan traffic. Finally, the downwind sites were believed to best representRCOfor Auckland City overall (11 ± 1 ppb ppm−1). We demonstrate that the initial discrepancy between the downwindRCOand Auckland's estimated daytime inventoryRCO(15 ppb ppm−1) can be attributed to an overestimation in inventory traffic CO emissions. After revision based on our observed motorwayRCO, the revised inventoryRCO(12 ppb ppm−1) is consistent with our observations.This article is part of the Theo Murphy meeting issue 'Radiocarbon in the Anthropocene'.
Ovine MyD88 have active role in host resistance againstHaemonchus contortusinfection
Authors: Banerjee Samiddha , Pal Aruna , Pal Abantika , Chatterjee Jayanta 
Published: October 2023

AbstractHost resistance against parasitic infestation is quite important to study in current days, since till date no effective vaccines against parasites have been developed. Moreover, indiscrimate use of regular deworming as a practice may lead to the development of resistance to antihelmiths (as in case of antibiotic resistance against bacteria) or development of antihelminth resistant strains among dreadly parasites. In this present study, we attempt to explore immune response gene againstHaemonchus contortusas dreadly parasite against sheep model. In our lab, we have already detected some of such promising genes, namely RIGI (earlier known antiviral in action), CD14, IL6 and IL10 (earlier known antibacterial in action). In this current publication, we have explored the role of MyD88 in mediating resistance against parasitic infestation. We have characterized ovine MyD88 molecule, identified important domain, analyzed molecular docking, identified the binding site withH. contortusthroughin silicostudies, network and pathway analysis, followed by differential mRNA expression profiling, ultimate confirmation through immunohistochemistry. Identification of immune response genes against parasites may lead to immunomodulation, genomic selection, gene therapy or even development of disease resistant stock of sheep through gene editing approach.
The prevalence, trends and heterogeneity in maternal smoking around birth between the 1930s and 1970s
Authors: von Hinke Stephanie , James Jonathan , Sorensen Emil , Sievertsen Hans H. , Vitt Nicolai 
Published: October 2023

AbstractThis paper shows the prevalence, trends and heterogeneity in maternal smoking around birth in the United Kingdom, focusing on the war and post-war reconstruction period in which there exists surprisingly little systematic data on (maternal) smoking behaviours. Within this context, we highlight relevant events, the release of new information about the harms of smoking, and changes in (government) policy aimed at reducing smoking prevalence. We show stark changes in smoking prevalence over a 30-year period, highlight the onset of the social gradient in smoking, as well as genetic heterogeneities in smoking trends.
Cost-effectiveness of CTC guided chemo- or endocrine therapy in ER+ HER2- metastatic breast cancer – results from a randomized controlled multicenter trial
Authors: Berghuis A.M.S. , Koffijberg H. , Pouwels X.G.L.V. , Berger F. , Alix-Panabières C. , Jacot W. , Pierga J.Y. , Bidard F.C. , IJzerman M.J. 
Published: October 2023

AbstractPatients with metastatic, Estrogen Receptor (ER) positive, HER2-negative, breast cancer, before initiating CDK4/6 inhibitors, receive either single agent endocrine- or chemotherapy based on their clinical risk. In this first-ever trial-based economic evaluation of Circulating Tumor Cells (CTCs), the cost-effectiveness of standardizing the prescription of endocrine- or chemotherapy using a CTC count threshold (with >5 CTCs/7.5mL indicative of unfavorable disease outcomes) was compared to current clinical practice. N=755 ER+ HER2-patients, enrolled in 17 French centres, were randomized to CTC guided or standard of care and were treated according to either through the CTC score or clinical examination. Health state utilities were calculated by mapping the QLQ-C30 to EQ-5D utilities and used to calculate Quality-Adjusted Life Years (QALY) over a 2-year time horizon. Bootstrapping and additional sensitivity analyses were performed to quantify the impact of uncertainty. Health outcomes in both arms were similar, but costs were higher in the CTC guided arm (€19,403) compared to the usual care (€18,254), resulting in an ICER of €104,078/QALY in favor of usual care. However, when the analysis was performed for the clinically high- and low-risk groups separately, CTC enumeration could be a dominant strategy (cost saving) if treatment is de-escalated in clinically high-risk patients as indicated by CTC scores. However, the current analysis was based on the PFS and OS data reported in 2021 and long-term Overall Survival data is collected since then (JCO, 2023 in press). A further analysis of the health economic impact of CTC enumeration in clinically low and high-risk groups is therefore indicated.
Integration of a fasting-mimicking diet program in primary care for type 2 diabetes reduces the need for medication – a 12-month randomised controlled trial
Authors: van den Burg Elske L , Schoonakker Marjolein P , van Peet Petra G , van den Akker – van Marle Elske M , Lamb Hildo J , Longo Valter D , Numans Mattijs E , Pijl Hanno 
Published: October 2023

AbstractAims/hypothesisThe aim of this study was to evaluate the impact on metabolic control of the periodic use of a 5-day fasting-mimicking diet (FMD) program as an adjunct to usual care in people with type 2 diabetes under regular primary care surveillance.MethodsIn this randomised, controlled, assessor-blinded trial, people with type 2 diabetes using metformin only and/or diet alone for glycaemic control were randomised to receive 5-day cycles of FMD monthly as adjunct to regular care by their general practitioner or regular care only. Primary outcomes were changes in glucose-lowering medication and HbA1c levels after 12 months. Moreover, changes in use of glucose-lowering medication and/or HbA1c levels in individual participants were combined to yield a clinically relevant primary outcome measure (‘glycaemic management’), categorized as improved, stable or deteriorated after one year of follow-up.Results100 individuals with type 2 diabetes, age 18-75 years, and BMI > 27 kg/m2, were randomised to the FMD (n=51) or control group (n=49). Eight FMD participants and ten controls were lost to follow-up. In complete case intention-to-treat analyses, the mean medication effect score (MES) significantly declined in patients receiving FMD as compared to controls (FMD −0.2 ± 0.3 vs controls +0.2 ± 0.4, p<0.0001) in the face of similar changes of HbA1c adjusted for MES (FMD −0.4 ± 0.8 % vs controls +0.2 ± 0.8 %, p=0.0021). Glycaemic management improved in 53% of participants using FMD vs 8% of controls, remained stable in 23% vs 33%, and deteriorated in 23% vs 59% (p<0.0001).Conclusions/interpretationIntegration of a monthly FMD program in regular primary care for people with type 2 diabetes who use metformin only and/or diet alone for glycaemic control reduces the need for glucose-lowering medication and appears to be safe in routine clinical practice.Trial registrationClinicalTrials.gov:NCT03811587
mRNA cap-binding protein eIF4E1 is a novel regulator ofToxoplasma gondiilatency
Authors: Holmes Michael J. , Bastos Matheus S. , Dey Vishakha , Severo Vanessa , Wek Ronald C. , Sullivan William J. 
Published: October 2023

AbstractThe protozoan parasiteToxoplasma gondiicauses serious opportunistic disease due to its ability to persist in patients as latent tissue cysts. The molecular mechanisms coordinating conversion between proliferative parasites (tachyzoites) and dormant cysts (bradyzoites) are not fully understood. We previously showed that phosphorylation of eIF2α accompanies bradyzoite formation, suggesting that this clinically relevant process involves regulation of mRNA translation. In this study, we investigated the composition and role of eIF4F multi-subunit complexes in translational control. Using CLIPseq, we find that the cap-binding subunit, eIF4E1, localizes to the 5’-end of all tachyzoite mRNAs, many of which show evidence of stemming from heterogenous transcriptional start sites. We further show that eIF4E1 operates as the predominant cap-binding protein in two distinct eIF4F complexes. Using genetic and pharmacological approaches, we found that eIF4E1 deficiency triggers efficient spontaneous formation of bradyzoites without stress induction. Consistent with this result, we also show that stress-induced bradyzoites exhibit reduced eIF4E1 expression. Overall, our findings establish a novel role for eIF4F in translational control required for parasite latency and microbial persistence.SignificanceToxoplasma gondiiis an opportunistic pathogen of importance to global human and animal health. There are currently no chemotherapies targeting the encysted form of the parasite. Consequently, a better understanding of the mechanisms controlling encystation are required. Here we show that the mRNA cap-binding protein, eIF4E1, is involved in regulating the encystation process. Encysted parasites reduce eIF4E1 levels and depletion of eIF4E1 decreases the translation of ribosome-associated machinery and drivesToxoplasmaencystation. Together, these data reveal a new layer of mRNA translational control that regulates parasite encystation and latency.
RNA Infrastructure Profiling Illuminates Transcriptome Structure in Crowded Spaces
Authors: Xiao Lu , Fang Linglan , Kool Eric T. 
Published: October 2023

AbstractRNAs can fold into compact three-dimensional structures, and most RNAs undergo protein interactions in the cell. These compact and occluded environments can block the ability of structure-probing agents to provide useful data about the folding and modification of the underlying RNA. The development of probes that can analyze structure in crowded settings, and differentiate the proximity of interactions, can shed new light on RNA biology. To this end, here we employ 2,-OH-reactive probes that are small enough to access folded RNA structure underlying many close molecular contacts within cells, providing considerably broader coverage for intracellular RNA structural analysis. We compare reverse transcriptase stops in RNA-Seq data from probes of small and standard size to assess RNA-protein proximity and evaluate solvent-exposed tunnels adjacent to RNA. The data are analyzed first with structurally characterized complexes (human 18S and 28S RNA), and then applied transcriptome-wide to polyadenylated transcripts in HEK293 cells. In our transcriptome profile, the smallest probe acetylimidazole (AcIm) yields 80% greater structural coverage than larger conventional reagent NAIN3, providing enhanced structural information in hundreds of transcripts. We further show that acetyl probes provide superior signals for identifying m6A modification sites in transcripts, and provide information regarding methylation sites that are inaccessible to a larger standard probe. RNA infrastructure profiling (RISP) enables enhanced analysis of transcriptome structure, modification, and interactions in living cells, especially in spatially crowded settings.
Predicting global herbicide resistance hotspots using a 30-year-old database and machine-learning techniques
Authors: Brocklehurst Neil , Liu Chun 
Published: October 2023

AbstractThe evolution of herbicide resistance in weeds is a problem affecting both food production and ecosystems. Numerous factors affect selection towards herbicide resistance, making it difficult to anticipate where, under what circumstances, and under what timeframe, herbicide resistance is likely to appear. Using the International Herbicide-Resistant Weed Database to provide data on locations and situations where resistance has occurred, we trained models to predict where resistance is most likely in future. Validation of the global models with historical data found a prediction accuracy of up to 78%, while for well-sampled regions, such as Australia, the model correctly predicted more than 95% of instance of resistance and sensitivity. Applying the models to predict instances of resistance over the next decade, future hotspots were detected in North and South America and Australia. Species such asConyza canadensis,Eleusine indica, andLactuca serriolaare expected to show substantial increases in the number of resistance occurrences. The results highlight the potential of machine-learning approaches in predicting future resistance hotspots and urge more efforts in resistance monitoring and reporting to enable improved predictions. Future work incorporating dimensions such as weed traits, phylogeny, herbicide chemistry, and farming practices could improve the predictive power of the models.
Visualisation of gene expression within the context of tissues: an X-ray computed tomography-based multimodal approach
Authors: Kairišs Kristaps , Sokolova Natalia , Zilova Lucie , Schlagheck Christina , Reinhardt Robert , Baumbach Tilo , Faragó Tomáš , van de Kamp Thomas , Wittbrodt Joachim , Weinhardt Venera 
Published: October 2023

AbstractThe development of an organism is orchestrated by the spatial and temporal expression of genes. Accurate visualisation of gene expression patterns in the context of the surrounding tissues offers a glimpse into the mechanisms that drive morphogenesis. We developed correlative light-sheet fluorescence microscopy and X-ray computed tomography approach to map gene expression patterns to the whole organism’s 3D anatomy at cellular resolution. We show that this multimodal approach is applicable to gene expression visualised by protein-specific antibodies and fluorescence RNAin situhybridisation, offering a detailed understanding of individual phenotypic variations in model organisms. Furthermore, the approach provides a unique possibility to identify tissues together with their 3D cellular and molecular composition in anatomically less-definedin vitromodels, such as organoids. We anticipate that the visual and quantitative insights into the 3D distribution of gene expression within tissue architecture, by the multimodal approach developed here, will be equally valuable for reference atlases of model organisms development, as well as for comprehensive screens and morphogenesis studies ofin vitromodels.
Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants
Authors: Frei Lester , Gao Beichen , Han Jiami , Taft Joseph M. , Irvine Edward B. , Weber Cédric R. , Kumar Rachita K. , Eisinger Benedikt N. , Reddy Sai T. 
Published: October 2023

ABSTRACTMost COVID-19 antibody therapies rely on binding the SARS-CoV-2 receptor binding domain (RBD). However, heavily mutated variants such as Omicron and its sublineages, which are characterized by an ever increasing number of mutations in the RBD, have rendered prior antibody therapies ineffective, leaving no clinically approved antibody treatments for SARS-CoV-2. Therefore, the capacity of therapeutic antibody candidates to bind and neutralize current and prospective SARS-CoV-2 variants is a critical factor for drug development. Here, we present a deep learning-guided approach to identify antibodies with enhanced resistance to SARS-CoV-2 evolution. We apply deep mutational learning (DML), a machine learning-guided protein engineering method to interrogate a massive sequence space of combinatorial RBD mutations and predict their impact on angiotensin-converting enzyme 2 (ACE2) binding and antibody escape. A high mutational distance library was constructed based on the full-length RBD of Omicron BA.1, which was experimentally screened for binding to the ACE2 receptor or neutralizing antibodies, followed by deep sequencing. The resulting data was used to train ensemble deep learning models that could accurately predict binding or escape for a panel of therapeutic antibody candidates targeting diverse RBD epitopes. Furthermore, antibody breadth was assessed by predicting binding or escape to synthetic lineages that represent millions of sequences generated usingin silicoevolution, revealing combinations with complementary and enhanced resistance to viral evolution. This deep learning approach may enable the design of next-generation antibody therapies that remain effective against future SARS-CoV-2 variants.
A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions
Authors: Dankwa Sedem , Kosman Christina , Dennis Maria , Giorgi Elena E. , Vuong Kenneth , Pahountis Ioanna , Garza Ashley , McCarthy Janice , Mayer Bryan T. , Ngo Julia T. , Enemuo Chiamaka A. , Carnathan Diane G. , Stanfield-Oakley Sherry , Berendam Stella J. , Weinbaum Carolyn , Engelman Kathleen , Magnani Diogo M. , Chan Cliburn , Ferrari Guido , Silvestri Guido , Amara Rama R. , Chahroudi Ann , Permar Sallie R. , Fouda Genevieve G. , Goswami Ria 
Published: October 2023

ABSTRACTTo eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple bNAb combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robustin vitroneutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy (PE) of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has a predicted PE≥90% against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.