bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline cancer gene expression quantitative trait loci influence local and global tumor mutations
Authors: Liu Yuxi , Gusev Alexander , Kraft Peter 
Published: August 2022

AbstractSomatic mutations drive cancer development and are relevant to patients’ response to treatment. Emerging evidence shows that variations in the somatic genome can be influenced by the germline genetic background. However, the mechanisms underlying these germline-somatic associations remain largely obscure. We hypothesized that germline variants can influence somatic mutations in a nearby cancer gene (“local impact”) or a set of recurrently mutated cancer genes across the genome (“global impact”) through their regulatory effect on gene expression. We integrated tumor targeted sequencing from 12,413 patients across 11 cancer types in the Dana-Farber Profile cohort with germline cancer gene expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression Project. We identified variants that upregulate ATM expression which are also associated with a decreased risk of having somatic ATM mutations across 8 cancer types (P = 3.43 × 10−5). We also identified GLI2, WRN, and CBFB eQTL that are associated with global tumor mutational burden of cancer genes in ovarian cancer, glioma, and esophagogastric carcinoma, respectively (P < 3.45 × 10−6). An EPHA5 eQTL was associated with the number of mutations in cancer genes specific to colorectal cancer, and eQTL associated with expression of APC, WRN, GLI1, FANCA, and TP53 were associated with mutations in genes specific to endometrial cancer (P < 1.73 × 10−5). Our findings provide evidence for the germline-somatic associations mediated through expression of specific cancer genes and open new avenues for research on the underlying biological processes, especially those related to immunotherapy responses.
Immune protection against SARS-CoV-2 re-reinfection and immune imprinting
Authors: Chemaitelly Hiam , Ayoub Houssein H. , Tang Patrick , Hasan Mohammad R. , Coyle Peter , Yassine Hadi M. , Al-Khatib Hebah A. , Smatti Maria K , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J. 
Published: August 2022

AbstractWe investigated epidemiological evidence for immune imprinting by comparing incidence of re-reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) reinfection after a pre-Omicron primary infection (designated as the reinfection cohort), to incidence of reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) primary infection (designated as the primary-infection cohort). This was done using a matched, retrospective cohort study that emulated a randomized “target trial”. Vaccinated individuals were excluded. Associations were estimated using Cox proportional-hazard regression models. Cumulative incidence of infection was 1.1% (95% CI: 0.8-1.4%) for the reinfection cohort and 2.1% (95% CI: 1.8-2.3%) for the primary-infection cohort, 135 days after the start of follow-up. The adjusted hazard ratio (aHR) for infection was 0.52 (95% CI: 0.40-0.68), comparing incidence in the reinfection cohort to that in the primary-infection cohort. The aHR was 0.59 (95% CI: 0.40-0.85) in a subgroup analysis in which primary infection in the reinfection cohort was restricted to only the index virus or Alpha variant. In the first 70 days of follow-up, when incidence was dominated by BA.2, the aHR was 0.92 (95% CI: 0.51-1.65). However, cumulative incidence curves diverged when BA.4/BA.5 subvariants dominated incidence (aHR, 0.46 (95% CI: 0.34-0.62)). There was no evidence that immune imprinting compromises protection against Omicron subvariants. However, there was evidence that having two infections, one with a pre-Omicron variant followed by one with an Omicron subvariant, elicits stronger protection against future Omicron-subvariant reinfection than having had only one infection with an Omicron subvariant.
Design and Analysis of Outcomes following SARS-CoV-2 Infection in Veterans
Authors: Smith Valerie A. , Berkowitz Theodore S. Z. , Hebert Paul , Wong Edwin S. , Niederhausen Meike , Pura John A. , Berry Kristin , Green Pamela , Korpak Anna , Fox Alexandra , Baraff Aaron , Hickok Alex , Shahoumian Troy A , Bohnert Amy S.B. , Hynes Denise , Boyko Edward J. , Ioannou George N. , Iwashyna Theodore J. , Bowling C. Barrett , O’Hare Ann M. , Maciejewski Matthew L. 
Published: August 2022

AbstractBackgroundUnderstanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs’ (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population.MethodsIn a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes.ResultsFrom an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 38 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%).ConclusionsThis successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.
Hospital bed capacity across in Tunisia hospital during the first four waves of the COVID-19 pandemic: A descriptive analysis
Authors: BenMiled Slimane , Borgi Chiraz , Hsairi Mohamed , Somrani Naoufel , Kebir Amira 
Published: August 2022

AbstractBackgroundOn March 11, 2020, WHO announced that the COVID-19 epidemic had passed the pandemic stage, indicating its spread over several continents. Tunisia’s containment and targeted screening strategy corresponded to the first WHO guidelines. Since then, public health policy has been more flexible and focused on the management of hospital beds.ObjectiveOur aims are to analyze bed occupancies for public hospitals and time delay reponse from the health care system in regard to the epidemiological situation.MethodsWe have analyzed the evolution of daily cases in relation to the different NPI actions undertaken by the Tunisian Government between March 2019 and February 2022 using the CoMo model. We have also studied the flexibility of the O2 and ICU public hospital bed occupancies. We have used three distinct indices to assess this flexibility: the Ramp Duration Until the Peak (RDUP), which measures the duration of the wave/bed allocation effort. The Ramp Growth Until the Peak (RGUP), measures the peak height, and Ramp Rate Until the Peak (RRUP) measures the growth rate of the wave. Also, in order to evaluate the government response efficacy, we have calculated the time delay at the start (resp. at peak) of each two waves.ResultsThe evolution of the epidemic in Tunisia was divided into two phases, the first of which corresponded to the initial wave, during which the pandemic was controlled due to very strong NPI actions. The second phase was distinguished by a progressive relaxation of measures and an increase in wave intensity.ICU bed availability has followed the demand for beds, while ICU bed occupancy has always been higher than 85% with a maximum of 97%.In terms of bed distribution, the government’s response was slow (9.4 days for the 02 beds and 18.2 days for the ICU beds). The same may be said for the reaction in terms of bed reallocation in the original departments (16 days for ICU beds and 10.6 days for O2 beds)..ConclusionWe were able to examine the responsiveness of the system as a whole for all of Tunisia’s public hospitals by measuring the flexibility and bed margin. With this research, decision makers will be able to assess their response capabilities in the event of current pandemic, as well as a future one.
Using geographic information systems to link population estimates to wastewater surveillance data in New York State, USA
Authors: Hill Dustin T. , Larsen David A. 
Published: August 2022

AbstractSewer systems provide many services to communities that have access to them beyond removal of waste and wastewater. Understanding of these systems’ geographic coverage is essential for wastewater-based epidemiology (WBE), which requires accurate estimates for the population contributing wastewater. Reliable estimates for the boundaries of a sewer service area or sewershed can be used to link upstream populations to wastewater samples taken at treatment plants or other locations within a sewer system. These geographic data are usually managed by public utilities, municipal offices, and some government agencies, however, there are no centralized databases for geographic information on sewer systems. We created a database for all municipal sewersheds in New York State for the purpose of supporting statewide wastewater surveillance efforts to support public health. We used a combination of public tax records with sewer access information, physical maps, and municipal records to organize and draw digital boundaries compatible with geographic information systems. The methods we employed to create these data will be useful to inform similar efforts in other jurisdictions and the data have many public health applications as well as being informative for water/environmental research and infrastructure projects.
Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation
Authors: McHenry Michael L , Simmons Jason , Hong Hyejeong , Malone LaShaunda L , Mayanja-Kizza Harriet , Bush William S. , Boom W. Henry , Hawn Thomas R , Williams Scott M. , Stein Catherine M. 
Published: August 2022

AbstractBackgroundTuberculosis (TB) remains a major public health problem globally, even compared to COVID-19. Genome-wide studies have failed to discover genes that explain a large proportion of genetic risk for adult pulmonary TB, and even fewer have examined genetic factors underlying TB severity, an intermediate trait impacting disease experience, quality of life, and risk of mortality. No prior severity analyses used a genome-wide approach.Methods and FindingsAs part of our ongoing household contact study in Kampala, Uganda, we conducted a genome-wide association study (GWAS) of TB severity measured by TBScore, in two independent cohorts of culture-confirmed adult TB cases (n=149 and n=179). We identified 3 SNPs (P<1.0 × 10-7) including one on chromosome 5, rs1848553, that was GWAS significant (meta-analysis p=2.97×10-8). All three SNPs are in introns of RGS7BP and have effect sizes corresponding to clinically meaningful reductions in disease severity. RGS7BP is highly expressed in blood vessels and plays a role in infectious disease pathogenesis. Other genes with suggestive associations defined gene sets involved in platelet homeostasis and transport of organic anions. To explore functional implications of the TB severity-associated variants, we conducted eQTL analyses using expression data from Mtb-stimulated monocyte-derived macrophages. A single variant (rs2976562) associated with monocyte SLA expression (p=0.03) and subsequent analyses indicated that SLA downregulation following MTB stimulation associated with increased TB severity. Src Like Adaptor (SLAP-1), encoded by SLA, is highly expressed in immune cells and negatively regulates T cell receptor signaling, providing a potential mechanistic link to TB severity.ConclusionsThese analyses reveal new insights into the genetics of TB severity with regulation of platelet homeostasis and vascular biology being central to consequences for active TB patients. This analysis also reveals genes that regulate inflammation can lead to differences in severity. Our findings provide an important step in improving TB patient outcomes.
Cost-utility analysis comparing ocrelizumab vs rituximab in the treatment of relapsing-remitting multiple sclerosis: The Colombian perspective
Authors: Navarro Cristian Eduardo , Betancur John Edison , Porras-Ramírez Alexandra 
Published: August 2022

AbstractIntroductionSince 2017, the ocrelizumab is available to treat patients with relapsing-remitting multiple sclerosis (RRMS), together with rituximab, they have a similar effectiveness but different costs. In this context, the added value provided by cost-effectiveness estimators for decision-making and drug prescription can be considered.Objectiveto determine the cost-utility of ocrelizumab versus rituximab in patients with RRMS, from the perspective of the Colombian health system.Methodologycost-utility study based on a Markov model, with a 50-year horizon and payer perspective. The currency was the US Dollar (USD) for the year 2019, with a threshold of $5,180 USD defined for Colombian health system. The model used annual cycles according to the health status determined by the disability scale. Direct costs were considered, and the incremental cost-effectiveness ratio (ICER) per 1 quality-adjusted life year (QALY) gained was used as the outcome measure. A discount rate of 5% was applied for costs and outcomes. Multiple one-way deterministic sensitivity analyzes and 10,000 modeling through Monte Carlo simulation were performed.Resultsfor the treatment of patients with RRMS, ocrelizumab versus rituximab had an ICER of $73,652 USD for each QALY gained. After 50 years, 1 subject treated with ocrelizumab earns 4.8 QALYs more than 1 subject treated with rituximab, but at a higher cost of $521,759 USD vs $168,752 USD, respectively. Ocrelizumab becomes a cost-effective therapy when its price is discounted >86%, or there is a high willingness to pay.ConclusionsOcrelizumab was not a cost-effective drug compared with rituximab to treat patients with RRMS in Colombia.
Label-free virus-antibody interaction monitoring in real time by common-path interferometry
Authors: Alhaddad Samer , Bey Houda , Thouvenin Olivier , Boulanger Pascale , Boccara Claude , Izeddin Ignacio , Boccara Martine 
Published: August 2022

ABSTRACTViruses can affect all life forms, raising concerns about virus detection and quantification of small nanoparticles. In this paper we use a label-free, full-field, incoherently illuminated common path interferometric method to detect, track, and quantify biotic nanoparticles. The detection consists of amplifying the light scattered by single nanoparticles in the sample solution. Then, the use of single-particle tracking analysis is used to monitor the change in particle diffusive mobility. With this approach, the recognition signature of T5 phages with purified antibodies targeting the major capsid protein is detected in a few minutes. We also tracked the interaction between SPP1 phages and physiological non-purified serum-containing multiples antibodies molecules. The first interactions occur after around one minute, and the recognition signature is detectable after minutes. In addition, we have been able to differentiate two populations of similar size of empty and full (encapsulating DNA) capsids of T5 in a heterogeneous solution demonstrating the robustness of this label-free detection approach. Furthermore, by combining the diffusion coefficient to the number of tracked particles, we were able to estimate the affinity of the virus-antibodies reaction.
Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection
Authors: Chen Rui , Fulton Kelly M. , Tran Anh , Duque Diana , Kovalchik Kevin , Caron Etienne , Twine Susan M. , Li Jianjun 
Published: August 2022

AbstractWe present an integrated immunopeptidomics and proteomics study of SARS-Cov-2 infection to comprehensively decipher the changes in host cells in response to viral infection. Our results indicated that innate immune response in Calu-3 cells was initiated by TLR3, followed by activation of interferon signaling pathway. Host cells also present viral antigens to the cell surface through both Class I and Class II MHC system for recognition by adaptive immune system. SARS-Cov-2 infection led to the disruption of antigen presentation as demonstrated by higher level of HLA proteins from the flow-through of MHC immunoprecipitation. Glycosylation analysis of HLA proteins from the elution and flow-through of immunoprecipitation revealed that the synthesis and degradation of HLA protein was affected by SARS-Cov-2 infection. This study provided many useful information to study the host response to SARS-Cov-2 infection and would be helpful for the development of therapeutics and vaccine for Covid-19 and future pandemic.
Sensitivity to naturalistic texture relies primarily on high spatial frequencies
Authors: Lieber Justin D. , Lee Gerick M. , Majaj Najib J. , Movshon J. Anthony 
Published: August 2022

AbstractNatural images contain information at multiple spatial scales. Although we understand how early visual mechanisms split multi-scale images into distinct spatial frequency channels, we do not know how the outputs of these channels are processed further by mid-level visual mechanisms. We have recently developed a naturalness discrimination task that uses synthesized, multi-scale textures to isolate these mid-level mechanisms (Freeman et. al. 2013). Here, we use three experimental manipulations (image blur, image rescaling, and eccentric viewing) to show that naturalness sensitivity is strongly dependent on image features at highobjectspatial frequencies (measured in cycles/image). As a result, sensitivity depends on atexture acuity limit, a property of the visual system that sets the highestretinalspatial frequency (measured in cycles/degree) that can be used to solve the task. A model observer analysis shows that high object spatial frequencies carry more task-relevant information than low object spatial frequencies. Comparing the outcome of this analysis with human performance reveals that human observers’ efficiency is similar for all object spatial frequencies. We conclude that the mid-level mechanisms that underlie naturalness sensitivity effectively extract information from all image features below the texture acuity limit, regardless of their retinal and object spatial frequency.
A neural signature of reward
Authors: Chang Luke J. , Li Xiao , Nguyen Kenny , Ranger Maxwell , Begunova Yelyzaveta , Chen Pin-Hao A. , Castrellon Jaime J. , Samanez-Larkin Gregory R. , Zald David H. , Fareri Dominic S. , Delgado Mauricio R. , Tomova Livia 
Published: August 2022

AbstractUsing a neurometric approach, we identify and validate a neural signature of reward encoded in a distributed pattern of brain activity using data collected from 21 different studies (N = 2,691). Our model can discriminate between receiving rewards from punishments in completely independent data with 99% accuracy and includes weights located in regions containing a high density of D2/D3 receptors. The model exhibits strong generalizability across a range of tasks probing reward, and a high degree of specificity for reward compared to non-reward constructs. We demonstrate several applications of how this model can infer psychological states of positive affect in the absence of self report. The model is sensitive to changes in brain activity following causal manipulations of homeostatic states, can uncover individual preferences for loss-aversion, and can be used to identify positive affective experiences when watching a television show. Our results suggest that there is a shared neural signature of reward elicited across these different task contexts.
COVID-19 Contact Tracing Analysis with Bluetooth Technology Using Raspberry Pis
Authors: Zhang Dean 
Published: August 2022

AbstractContact tracing, a method for detecting and preventing the spread of a disease, can become more efficient by becoming automated, rather than being done manually. Bluetooth based contact tracing is a potential method for creating an automated method for contact tracing. However, Bluetooth signals cannot always predict something with complete accuracy due to many subtle obstructions. Received signal strength indicator (RSSI), a value produced when Bluetooth devices send and receive signals, generated from Raspberry Pis can predict the distance between the two devices. By running many experiments with variations of obstructions, I was able to successfully create models to correlate RSSI values and distance with a potential success rate of 91.973%. For my research, a success is determined to be anything but a false negative. Despite the limitations when conducting my research, the inaccuracies of my results prove Bluetooth based contact tracing to not be a reliable method for determining people who have been in contact with an index case in the real world.
The role of the parietal lobe in task-irrelevant suppression during learning
Authors: Contò F. , Tyler S , Paletta P. , Battelli L. 
Published: August 2022

AbstractBackgroundAttention optimizes the selection of visual information, while suppressing irrelevant visual input through cortical mechanisms that are still unclear. We set to investigate these processes using an attention task with an embedded to-be-ignored interfering visual input.ObjectiveWe delivered electrical stimulation to attention-related brain areas to modulate these facilitatory/inhibitory attentional mechanisms. We asked whether training on a task while being simultaneously exposed to visual features from a different task tested at baseline and post-training might influence performance on the baseline task.MethodsIn Experiment one, subjects performed an orientation discrimination (OD) task using a pair of gratings presented at individual’s psychophysical threshold. We then trained participants over multiple sessions on a temporal order judgment task (TOJ), using the exact same gratings but presented with different time offsets. On the last session we re-tested OD. We coupled training with transcranial random noise stimulation (tRNS) over the parietal cortex, the human middle temporal area or sham, in three separate groups. In Experiment two, subjects performed the same OD task at baseline and post-training, while tRNS was delivered at rest during training.ResultsResults showed that tRNS over parietal cortex facilitated learning of the trained task. Moreover, we found a detrimental effect on OD when subjects received parietal tRNS coupled with training, but a benefit on OD when subjects received stimulation while at rest.ConclusionsThese results clearly indicate that task-irrelevant information is actively suppressed during learning, and that this prioritization mechanism of selection likely resides in the parietal cortex.