bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Neck PET/CT Positivity on Survival Outcomes—Visual and Quantitative Assessment
Authors: Stack Brendan C. , Duan Fenghai , Romanoff Justin , Sicks JoRean D. , Subramaniam Rathan M. , Lowe Val J. 
Published: December 2022

Introduction
FDG PET/CT was prospectively studied in 287 cN0 head and neck cancer patients in ACRIN 6685, and additional analysis of neck FDG uptake upon recurrence-free survival (RFS) and overall survival (OS) was performed.

Patients and Methods
Two hundred eight had analyzable data. Survival analysis was performed to compare RFS and OS based on neck FDG visual assessment (VA) and SUVmax. For SUVmax, the optimal thresholds were calculated using conditional inference trees on a randomly selected 70% training data set and validated using the remaining 30% of data. Kaplan-Meier curves with log-rank tests were generated for the patient groups based on VA and optimal SUVmax thresholds, and the hazards ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Hypothesis testing was set at a significance level of 0.05.

Results
A total of 73.9% of bilateral cN0 and 50.0% of unilateral cN0 were alive at the end of the study with the remaining being dead or lost to follow-up. Overall survival median follow-up time was 24.0 months (interquartile range, 15.8–25.3; range, 0–37.0). A total of 63.3% of bilateral cN0 and 42.5% of unilateral cN0 patients remained disease free during the study. Recurrence-free survival median follow-up time was 23.9 months (interquartile range, 12.4–25.2; range, 0–35.6). Visual assessment of necks by our panel of radiologists was significantly associated with RFS (HR [95% CI], 2.30 [1.10–4.79]; P = 0.02), but not with OS (HR [95% CI], 1.64 [0.86–3.14]; P = 0.13). The optimal SUVmax thresholds were 2.5 for RFS and 5.0 for OS. For SUVmax assessment, applying the optimal thresholds to the 30% test data yielded HRs (95% CIs) of 2.09 (0.61–7.14; P = 0.23) for RFS and 3.42 (1.03–11.41; P = 0.03) for OS. The SUVmax threshold of 5.0 was significantly associated with RFS (HR [95% CI], 5.92 [1.79–19.57]; P < 0.001).

Conclusions
Neck FDG uptake by VA is significant for RFS. An SUVmax threshold of 5.0 is significantly associated with OS and RFS.
APOEGenotype-specific Methylation Patterns are Linked to Alzheimer Disease Pathology and Estrogen Response
Authors: Panitch Rebecca , Sahelijo Nathan , Hu Junming ,   the Alzheimer’s Disease Neuroimaging Initiative, Nho Kwangsik , Bennett David A. , Lunetta Kathryn L. , Au Rhoda , Stein Thor D. , Farrer Lindsay A. , Jun Gyungah R. 
Published: December 2022

AbstractThe joint effects ofAPOEgenotype and DNA methylation on Alzheimer disease (AD) risk is relatively unknown. We conducted genome-wide methylation analyses using 2,021 samples in blood (91 AD cases, 329 mild cognitive impairment, 1,391 controls) and 697 samples in brain (417 AD cases, 280 controls). We identified differentially methylated levels in AD compared to controls in anAPOEgenotype-specific manner at 25 cytosine-phosphate-guanine (CpG) sites in brain and 36 CpG sites in blood. Additionally, we identified seven CpG sites in theAPOEregion containingTOMM40, APOE, andAPOC1genes with P<5×10−8betweenAPOEε4 carriers and non-carriers in brain or blood. In brain, the most significant CpG site hypomethylated in ε4 carriers compared to non-carriers) was from theTOMM40in the total sample, while most of the evidence was derived from AD cases. However, the CpG site was not significantly modulating expression of these three genes in brain. Three CpG sites from theAPOEwere hypermethylated inAPOEε4 carriers in brain or blood compared in ε4 non-carriers and nominally significant withAPOEexpression in brain. Three CpG sites from theAPOC1were hypermethylated in blood, which one of the 3 CpG sites significantly loweredAPOC1expression in blood using all subjects or ε4 non-carriers. Co-methylation network analysis in blood and brain detected eight methylation networks associated with AD andAPOEε4 status. Five of the eight networks included genes containing network CpGs that were significantly enriched for estradiol perturbation, where four of the five networks were enriched for the estrogen response pathway. Our findings provide further evidence of the role ofAPOEgenotype on methylation levels associated with AD, especially linked to estrogen response pathway.
Metabolite diversity amongProchlorococcusstrains belonging to divergent ecotypes
Authors: Kujawinski Elizabeth B. , Braakman Rogier , Longnecker Krista , Chisholm Sallie W. , Becker Jamie W. , Dooley Keven , Soule Melissa C. Kido , Swarr Gretchen J. , Halloran Kathryn 
Published: December 2022

Primary AbstractThe euphotic zone of the surface ocean contains distinct physical-chemical regimes that vary inversely in light and nutrient concentrations as a function of depth. The most numerous phytoplankter of the mid- and low-latitude ocean is the picocyanobacteriumProchlorococcus,which consists of ecologically distinct subpopulations (i.e., “ecotypes”). Ecotypes have different temperature, light and nutrient optima and display distinct relative abundances along gradients of these niche dimensions. As a primary producer,Prochlorococcusfixes and releases organic carbon to neighboring microbes as part of the microbial loop. However, little is known about the specific moleculesProchlorococcusaccumulates and releases or how these processes vary among its ecotypes. Here we characterize metabolite diversity ofProchlorococcusby profiling three ecologically-distinct cultured strains: MIT9301, representing a high-light adapted ecotype dominating shallow tropical and sub-tropical waters, MIT0801, representing a low-light adapted ecotype found throughout the euphotic zone and MIT9313, representing a low-light adapted ecotype relatively most abundant at the base of the euphotic zone. In both intracellular and extracellular metabolite profiles, we observe striking differences across strains in the accumulation and release of molecules. Some differences reflect variable genome content across the strains, while others likely reflect variable regulation of genetically-conserved pathways. In the extracellular profiles, we identify molecules that may serve as currencies inProchlorococcus’interactions with neighboring microbes and therefore merit further investigation.ImportanceApproximately half of the annual carbon fixation on Earth occurs in the surface ocean through the photosynthetic activities of phytoplankton such as the ubiquitous picocyanobacteriumProchlorococcus.Ecologically-distinct subpopulations ofProchlorococcus(or ecotypes) are central conduits of organic substrates into the ocean microbiome, thus playing important roles in surface ocean production. By measuring the chemical profile of three cultured ecotype strains, we observed striking differences in the likely chemical impact ofProchlorococcussubpopulations on their surroundings. Subpopulations differ along gradients of temperature, light and nutrient concentrations, suggesting that these chemical differences could affect carbon cycling in different ocean strata and should be considered in models ofProchlorococcusphysiology and marine carbon dynamics.
Novel Community-Based Rabies Surveillance (CBRS) In Urban Lilongwe City, Malawi
Authors: Mastala Precious Innocent , Tefera Melaku , Chiweta Edson , Nyamwanza Madeline , Kapalamula Thoko 
Published: December 2022

AbstractIntroductionRabies is a neglected tropical disease that is endemic to Malawi, killing almost 500 people every year. Domestic dogs are implicated as the main reservoir for rabies. However, there is limited capacity to detect canine rabies in the country, particularly in urban areas where there are high dog densities. The Lilongwe Society for the Protection and Care of Animals designed and implemented a canine community-based rabies surveillance (CBRS) in Lilongwe city between January and June 2020.ObjectivesThis study assessed the effectiveness of the CBRS program in canine rabies detection compared to the traditional passive routine surveillance data of the years between 2015 and 2019. Furthermore, the study determined rabies Post-Exposure Prophylaxis (PEP) issuance trends in emergent cases.MethodsSuspected rabies cases were recorded and followed. The dogs that were found alive were quarantined for 10 days for observation. Brain samples were collected post-mortem for direct-fluorescent antibody testing for antigen detection.ResultsThere were 610 suspected cases, and only 217 (39.2%) were followable. Out of these, 150 (62.8%) were followed. A total of 9 dogs (6%) tested positive, and there were 11 (7.3%) probable cases. This represents a 4.97-fold increase in rabies cases detected compared to the pre-surveillance period, with a resultant of 3.33 cases/month from 0.67 cases/month. The program also helped to initiate PEP treatment in exposed people. There were 141 bite victims and 136 (96.5%) reported for PEP. Out of these, 89 (65.4%) were from healthy bites and 33 (24.4%) from suspect cases indicating a 63.97% to 88.24% rate of irrelevant PEP issuance.ConclusionThe CBRS program established relevance in increasing canine rabies detection and subsequent prevention of related human infections. It also established a high rate of PEP issuance following healthy bites. Therefore, we recommend enhanced multi-sectoral collaborative efforts aimed at increasing rabies detection and optimizing PEP usage.One Health Impact StatementThis novel implementation research features a One Health approach, bringing together various stakeholders from the public and private sectors, as well as the community, in the effort to eradicate rabies. This collaboration provides synergy towards accelerating the identification of rabid animals in the community and effectively guides people to take the necessary precautions including prompt Post-Exposure Prophylaxis in cases of exposure, ultimately promoting health at the human-animal interface.
Crowdsourced partner services among men who have sex with men living with HIV: A pilot randomized controlled trial in China
Authors: Yan Xumeng , Tucker Joseph D. , Miller William C. , Tang Weiming 
Published: December 2022

AbstractBackgroundTo improve the uptake of HIV partner services (HIV PS) among men who have sex with men living with HIV (MLWH) in China, our team used a crowdsourcing approach to develop a tailored intervention package. This study assessed the acceptability, feasibility, and preliminary effectiveness of a crowdsourced HIV PS intervention compared to conventional HIV PS.MethodsThe study conducted a pilot two-arm randomized controlled trial (RCT) to compare the proportion of HIV testing among sexual partners of MLWH. Indexes in the control arm received conventional HIV PS using referral cards. Indexes in the intervention arm received a crowdsourced HIV PS intervention which included HIV self-testing kits for secondary distribution (HIVST-SD), digital education materials, and assisted PS via provider/contract referral. The primary outcomes were (1) intervention feasibility (i.e., the frequency of indexes using crowdsourced intervention components), (2) intervention acceptability (i.e., the evaluation of indexes on intervention components using Likert scales), and (3) the preliminary impact of the intervention (i.e., the proportion of partners getting HIV testing within three months of index enrollment). Descriptive analysis was conducted, and Chi-squared tests were used to test whether the proportional differences were significant.ResultsA total of 121 MSM newly diagnosed with HIV were enrolled between July 2021 and May 2022 in Guangzhou and Zhuhai, China, with 81 in the intervention arm and 40 in the control arm. The 3-month follow-up rates were 93% (75/81) and 83% (33/40), respectively. The crowdsourced intervention components were feasible, as 31 indexes received and 23 indexes used HIVST-SD, 6 indexes used provider-referral to notify 9 sexual partners, and indexes visited the digital educational materials 2.3 times on average. The intervention components also demonstrated acceptability, with HIVST-SD rated 4.4 out of 5 and the digital educational materials rated 4.1 out of 5. The proportion of partners getting HIV testing among all identified partners was 38% (65/171) in the intervention arm, compared to 27% (24/89) in the control arm. The difference was not statistically significant.ConclusionThe crowdsourced HIV PS intervention components were acceptable and feasible among Chinese MLWH and may improve the proportion of stable partners receiving HIV testing. Further implementation science research is needed to expand PS among key populations in low and middle-income countries.Clinical trial registration19-0496
Characterizing proteomic and transcriptomic features of missense variants in amyotrophic lateral sclerosis genes
Authors: Dilliott Allison A. , Rouleau Guy A. , Iqbal Sumaiya , Farhan Sali M.K. 
Published: December 2022

AbstractBackgroundWithin recent years, there has been a growing number of genes associated with amyotrophic lateral sclerosis (ALS), resulting in an increasing number of novel variants, particularly missense variants, many of which are of unknown clinical significance. Here, we leverage the sequencing efforts of the ALS Knowledge Portal (3,864 individuals with ALS and 7,839 controls) and Project MinE ALS Sequencing Consortium (4,366 individuals with ALS and 1,832 controls) to perform proteomic and transcriptomic characterization of missense variants in 24 ALS-associated genes.ResultsUsing predicted human protein structures from AlphaFold, we determined that missense variants carried by individuals with ALS were significantly enriched in β-sheets and α-helices, as well as in core, buried, or moderately buried regions. At the same time, we identified that hydrophobic amino acid residues, compositionally biased protein regions and protein-protein interaction regions are predominantly enriched in missense variants carried by individuals with ALS. Assessment of expression level based on transcriptomics also revealed enrichment of variants of high and medium expression across all tissues and within the brain. We further explored enriched features of interest using burden analyses to determine whether individual genes were driving the enrichment signal. A case study is presented forSOD1to demonstrate proof of concept of how enriched features may aid in defining variant pathogenicity.ConclusionsOur results present proteomic and transcriptomic features that are important indicators of missense variant pathogenicity in ALS and are distinct from features associated with neurodevelopmental disorders.
Visualizing Decisions and Analytics of Artificial Intelligence based Cancer Diagnosis and Grading of Specimen Digitized Biopsy: Case Study for Prostate Cancer
Authors: Singh Akarsh , Wan Michael , Harrison Lane , Breggia Anne , Christman Robert , Winslow Raimond L. , Amal Saeed 
Published: December 2022

1ABSTRACTThe rise in Artificial Intelligence (AI) and deep learning research has shown great promise in diagnosing prostate cancer from whole slide image biopsies. Intelligent application interface for diagnosis is a progressive way to communicate AI results in the medical domain for practical use. This paper aims to suggest a way to integrate state-of-the-art deep learning algorithms into a web application for visualizations of decisions and analytics of an AI based algorithms applied on cancer digitized specimen biopsies together with visualizing evidence and explanation of the decision using both image from the biopsy and textual data from Electronic Health Records (EHR). By creating smart visualizations of tissue biopsy images, from magnified regions to augmented sharper images along with image masks that highlight cancerous regions of tissue in addition to intelligent analytics and distribution charts related to cancer prediction, we aim to communicate these easily interpretable results to assist pathologists and concerned medical team to make better decisions for prostate cancer diagnosis as case study.
Seroprevalence of COVID-19 infection in a densely populated district in the eastern Democratic Republic of Congo
Authors: Irenge Leonid M. , Bulakali Homer M. , Akonkwa Arthur Irenge , Ambroise Jérôme , Gala Jean-Luc 
Published: December 2022

SummaryData on coronavirus disease 2019 (COVID-19) prevalence in the Democratic Republic of Congo (DRC) are scarce. We conducted a cross-sectional study to determine the seroprevalence of antibodies against anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the slum of Kadutu, city of Bukavu, between June and September 2021. The survey participants were all unvaccinated against SARS-CoV-2. The crude seroprevalence rate was adjusted to the known characteristics of the assay. Participants aged 15 to 49 years old made up 80 % of the population enrolled in the study (n=507; 319 women and 188 men). The overall crude and adjusted seroprevalence rates of antibodies for COVID-19 were 59.7 % (95 % CI 55.4 % - 63.9 %) and 84.0 % (95 % CI 76.2 % to 92.4 %), respectively. This seroprevalence rate indicates widespread dissemination of SARS-CoV-2 in these communities. COVID-19 symptoms were either absent or mild in more than half of the participants with antibodies for COVID-19 and none of the participants with antibodies for COVID-19 required hospitalization. These results suggest that SARS-CoV-2 spread did not appear to be associated with severe symptoms in the population of these settlements and that many cases went unreported in these densely populated locations. The relevance of vaccination in these communities should be thoroughly investigated.
Evaluation of Covid-19 Ag-RDTs self-testing in Lesotho and Zambia
Authors: Bresser M. , Erhardt R.M. , Shanaube K. , Simwinga M. , Mahlatsi P.A. , Belus J. , Schaap A. , Amstutz A. , Gachie T. , Glass T.R. , Kangolo B. , ‘Mota M.J. , Floyd S. , Katende B. , Klinkenberg E. , Ayles H. , Reither K. , Ruperez M. 
Published: December 2022

AbstractBackgroundThe use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (BRCCH-EDCTP COVID-19 Initiative) was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region.MethodsA cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 11 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants’ understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed.ResultsCognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.6% (404/414, 95% CI: 95.6-99.8) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively.ConclusionFindings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.
Maize phytocytokines and microbial-patterns trigger antagonistic features in co-incidence with wounding and fungal pathogens
Authors: Koenig Maurice , Moser Daniel , Leusner Julian , Depotter Jasper , Doehlemann Gunther , Villamil Johana Misas 
Published: December 2022

AbstractPhytocytokines are signalling peptides that activate immune responses and alarm bystander cells of danger. The pathways of phytocytokine perception and activation are thought to be shared between exogenous danger signals such as microbe-associated molecular patterns (MAMPs) and endogenous, passively released, damage-associated molecular patterns (DAMPs). However, downstream responses triggered by danger molecules and their effect in plant survival is still largely unknown. Here, we have identified three biologically active maize orthologues of phytocytokines previously described in other plants. The maize phytocytokines show common features with MAMPs, including the induction of immune related genes and activation of papain-like cysteine proteases. In contrast to MAMPs, the phytocytokines do not promote cell death in the presence of wounding. In infection assays with fungal pathogens of two different life styles we found that phytocytokines affect the development of disease symptoms, likely due to the activation of phytohormonal pathways. Collectively, our results show that phytocytokines and MAMPs trigger unique and antagonistic features of immunity. We propose a model in which phytocytokines activate immune responses partially similar to MAMPs but in contrast to microbial signals, they act as danger and survival molecules to the surrounding cells. Future studies will focus on the components determining the divergence of signalling outputs upon phytocytokine activation.
Nigral pathology contributes to microstructural integrity of striatal and frontal tracts in Parkinson’s disease
Authors: Lin Chen-Pei , Knoop Lydian EJ , Frigerio Irene , Bol John GJM , Rozemuller Annemieke JM , Berendse Henk W , Pouwels Petra JW , van de Berg Wilma DJ , Jonkman Laura E 
Published: December 2022

AbstractBackgroundMotor and cognitive impairment in Parkinson’s disease (PD) is associated with dopaminergic dysfunction that stems from substantia nigra (SN) degeneration and concomitant α-synuclein accumulation. Diffusion MRI can detect microstructural alterations of the SN and its tracts to (sub)cortical regions, but their pathological sensitivity is still poorly understood.ObjectiveTo unravel the pathological substrate underlying microstructural alterations of the SN, and its tracts to the dorsal striatum and dorsolateral prefrontal cortex (DLPFC) in PD.MethodsCombining post-mortemin-situMRI and histopathology, T1-weighted and diffusion MRI of 9 PD, 6 PD with dementia (PDD), 5 dementia with Lewy bodies (DLB), and 10 control donors were collected. From MRI, mean diffusivity (MD) and fractional anisotropy (FA) were derived from the SN, and tracts between the SN and caudate nucleus, putamen, and DLPFC. Phosphorylated-Ser129-α-synuclein and tyrosine hydroxylase immunohistochemistry was included to quantify nigral Lewy pathology and dopaminergic degeneration, respectively.ResultsCompared to controls, PD and PDD/DLB showed increased MD of the SN and SN-DLPFC tract, as well as increased FA of the SN-caudate nucleus tract. Both PD and PDD/DLB showed nigral Lewy pathology and dopaminergic loss compared to controls. Increased FA of the SN and SN-caudate nucleus tract was associated with SN dopaminergic loss, while increased MD of the SN-DLPFC tract was associated with increased SN Lewy neurite load.ConclusionsIn PD and PDD/DLB, diffusion MRI captures microstructural alterations of the SN and tracts to the dorsal striatum and DLPFC, which differentially associates with SN dopaminergic degeneration and Lewy neurite pathology.