bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Vaccination Gap in Admitted Trauma Patients: A Critical Opportunity
Authors: Turer Robert W , Chen Qingxia , Jones Ian D , Gondek Stephen P , Guillamondegui Oscar D , Dennis Bradley M
Published: April 2022

BACKGROUND:

Coronavirus disease 2019 (COVID-19) vaccination is the core strategy for pandemic management. We hypothesized that a vaccination gap might exist between emergency department (ED) patients admitted for trauma and other ED patients.

STUDY DESIGN:

This was an observational quality improvement study using electronic health record data at an academic level-1 trauma center. Participants were all patients presenting to the adult ED with a Tennessee home address between January 1 and June 1, 2021. We measured the proportional difference in vaccination between admitted trauma patients and other ED patients over time (by week) and association via Spearman’s rank correlation coefficient. Binary logistic regression facilitated covariate analysis to account for age, sex, race, home county, and ethnicity without and then with interaction between trauma admission and time. Geographic visual analysis compared county-level vaccination rates with odds of trauma admission by home county using a bivariate chloropleth map.

RESULTS:

The proportional difference in vaccination between trauma-admitted and other ED patients increased over time (Spearman’s = 0.699). Adjusting for age, sex, race, home county, and ethnicity, there was a statistically significant vaccination difference between trauma-admitted and other ED patients (odds ratio = 0.53, 95% CI 0.43–0.65, p < 0.0001). Geographic analysis revealed increased trauma admission odds and lower vaccination rates in surrounding counties compared with Davidson County.

CONCLUSIONS:

We observed a widening COVID-19 vaccination gap between trauma-admitted and other ED patients. Vaccine outreach during trauma admission may provide a valuable point of contact for unvaccinated patients.
Outcomes in Elderly Patients Undergoing Liver Transplantation Compared with Liver-Directed Ablative Therapy in Early-Stage Hepatocellular Carcinoma
Authors: Shah Malay B , Villagomez Rubio Diego A , Orozco Gabriel , Desai Siddharth , Ancheta Alexandre , Gupta Meera , Mei Xiaonan , Evers B Mark , Gedaly Roberto , Cannon Robert M
Published: April 2022

BACKGROUND:

Orthotopic liver transplantation (OLT) is the accepted treatment in patients with unresectable, early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. Due to increasing waitlist demand for OLT, determining optimal groups for transplant is critical. Elderly patients are known to have poorer postoperative outcomes. Considering the effectiveness of liver-directed therapies for HCC, we sought to determine whether elderly patients received survival benefit from OLT over liver-directed therapy alone.

STUDY DESIGN:

The National Cancer Database participant use file was used to analyze data between 2004 and 2017. Only patients ≥70 years of age who received OLT or liver-directed therapy alone were included. Patients with alpha-fetoprotein >500 ng/mL or missing alpha-fetoprotein values were excluded. Baseline demographic variables, model for end-stage liver disease score, and overall survival from time of diagnosis were collected. Descriptive statistics, Kaplan-Meier survival, Cox proportional hazards model, and propensity score matching were used.

RESULTS:

A total of 2,377 patients received ablative therapy alone, and 214 patients received OLT. Multivariable analysis and Kaplan-Meier showed that OLT conferred a significant survival benefit compared to liver-directed therapy alone. Age was also associated with a yearly 3% increase in risk of mortality. Propensity-matched analysis adjusting also demonstrated a significant survival benefit for elderly patients receiving OLT compared to liver-directed therapy alone.

CONCLUSION:

Despite increased age and associated comorbidities being factors associated with poor outcomes, OLT confers a survival advantage compared to liver-directed ablative therapies alone in selected elderly patients with HCC. OLT should be offered in medically appropriate elderly patients with HCC.
Resuscitative Endovascular Balloon Occlusion of the Aorta in Penetrating Trauma
Authors: Schellenberg Morgan , Owattanapanich Natthida , DuBose Joseph J , Brenner Megan , Magee Gregory A , Moore Laura J , Scalea Thomas , Inaba Kenji ,   The AAST PROOVIT Study Group
Published: April 2022

BACKGROUND:

Resuscitative endovascular balloon occlusion of the aorta (REBOA) achieves temporary hemorrhage control via aortic occlusion. Existing REBOA literature focuses on blunt trauma without a clearly defined role in penetrating trauma. This study compared clinical/injury data and outcomes after REBOA in penetrating vs blunt trauma.

STUDY DESIGN:

All patients in the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) database, an observational American Association for the Surgery of Trauma dataset of trauma patients requiring aortic occlusion, who underwent REBOA were included (January 2014 through February 2021). Study groups were defined by mechanism: penetrating vs blunt. Subgroup analysis was performed of patients arriving with vital signs. Univariable/multivariable analyses compared injuries and outcomes.

RESULTS:

Seven hundred fifty-nine patients underwent REBOA: 152 (20%) penetrating and 607 (80%) blunt. Patients undergoing penetrating REBOA were less severely injured (injury severity score 25 vs 34; p < 0.001). The most common hemorrhage source was abdominal in penetrating REBOA (79%) and pelvic in blunt REBOA (31%; p = 0.002). Penetrating REBOA was more likely to occur in the operating room (36% vs 17%) and less likely in the emergency department (63% vs 81%; p < 0.001). Penetrating REBOA used more zone I balloon deployment (76% vs 64%) and less zone III (19% vs 34%; p = 0.001). Improved or stabilized hemodynamics were less frequent after penetrating REBOA (41% vs 62%, p < 0.001; 23% vs 41%, p < 0.001). On subgroup analysis of patients arriving alive, improvement or stabilization in hemodynamics was similar between groups (87% vs 86%, p = 0.388; 77% vs 72%, p = 0.273). Penetrating REBOA was not independently associated with mortality (odds ratio 1.253; p = 0.776).

CONCLUSIONS:

Despite lower injury severity, REBOA was significantly less likely to improve or stabilize hemodynamics after penetrating trauma. Among patients arriving alive, however, outcomes were comparable, suggesting that penetrating REBOA may be most beneficial among patients with vital signs. Because hemorrhage source, catheter insertion setting, and deployment zone varied significantly between groups, existing blunt REBOA data may not be appropriately extrapolated to penetrating trauma. Further study of REBOA as a means of aortic occlusion in penetrating trauma is needed.
Novel Machine Learning Approach for the Prediction of Hernia Recurrence, Surgical Complication, and 30-Day Readmission after Abdominal Wall Reconstruction
Authors: Hassan Abbas M , Lu Sheng-Chieh , Asaad Malke , Liu Jun , Offodile Anaeze C , Sidey-Gibbons Chris , Butler Charles E
Published: April 2022

BACKGROUND:

Despite advancements in abdominal wall reconstruction (AWR) techniques, hernia recurrences (HRs), surgical site occurrences (SSOs), and unplanned hospital readmissions persist. We sought to develop, validate, and evaluate machine learning (ML) algorithms for predicting complications after AWR.

METHODS:

We conducted a comprehensive review of patients who underwent AWR from March 2005 to June 2019. Nine supervised ML algorithms were developed to preoperatively predict HR, SSOs, and 30-day readmission. Patient data were partitioned into training (80%) and testing (20%) sets.

RESULTS:

We identified 725 patients (52% women), with a mean age of 60 ± 11.5 years, mean body mass index of 31 ± 7 kg/m2, and mean follow-up time of 42 ± 29 months. The HR rate was 12.8%, SSO rate was 30%, and 30-day readmission rate was 10.9%. ML models demonstrated good discriminatory performance for predicting HR (area under the receiver operating characteristic curve [AUC] 0.71), SSOs (AUC 0.75), and 30-day readmission (AUC 0.74). ML models achieved mean accuracy rates of 85% (95% CI 80% to 90%), 72% (95% CI 64% to 80%), and 84% (95% CI 77% to 90%) for predicting HR, SSOs, and 30-day readmission, respectively. ML identified and characterized 4 unique significant predictors of HR, 12 of SSOs, and 3 of 30-day readmission. Decision curve analysis demonstrated that ML models have a superior net benefit regardless of the probability threshold.

CONCLUSIONS:

ML algorithms trained on readily available preoperative clinical data accurately predicted complications of AWR. Our findings support incorporating ML models into the preoperative assessment of patients undergoing AWR to provide data-driven, patient-specific risk assessment.
Predictive Role of Gut Microbiota in Weight Loss Achievement after Bariatric Surgery
Authors: Gutiérrez-Repiso Carolina , Garrido-Sánchez Lourdes , Alcaide-Torres Juan , Cornejo-Pareja Isabel , Ocaña-Wilhelmi Luis , García-Fuentes Eduardo , Moreno-Indias Isabel , Tinahones Francisco J
Published: April 2022

BACKGROUND:

Bariatric surgery induces changes in gut microbiota that have been suggested to contribute to weight loss and metabolic improvement. However, whether preoperative gut microbiota composition could predict response to bariatric surgery has not yet been elucidated.

STUDY DESIGN:

Seventy-six patients who underwent sleeve gastrectomy were classified according to the percentage of excess weight loss (%EWL) 1 year after surgery in the responder group: >50%EWL (n=50) and the nonresponder group: <50%EWL (n=26). Patients were evaluated before surgery, and 3 months and 1 year after surgery. Gut microbiota composition was analyzed before surgery (n=76) and 3 months after bariatric surgery (n=40).

RESULTS:

Diversity analysis did not show differences between groups before surgery or 3 months after surgery. Before surgery, there were differences in the abundance of members belonging to Bacteroidetes and Firmicutes phyla (nonresponder group: enriched in Bacteroidaceae, Bacteroides, Bacteroides uniformis, Alistipes finegoldii, Alistipes alistipes, Dorea formicigenerans, and Ruminococcus gnavus. Responder group: enriched in Peptostreptococcaceae, Gemmiger, Gemiger formicilis, Barnesiella, Prevotellaceae, and Prevotella; linear discriminant analysis >2; p < 0.05). Prevotella-to-Bacteroides ratio was significantly lower in the nonresponder group compared to the responder group (p = 0.048). After surgery, the responder group showed an enrichment in taxa that have been shown to have beneficial effects on host metabolism. Before surgery, PICRUSt analysis showed an enrichment in pathways involved in the biosynthesis components of the O-antigen polysaccharideunits in lipopolysaccharides in the nonresponder group.

CONCLUSIONS:

Preoperative gut microbiota could have an impact on bariatric surgery outcomes. Prevotella-to-Bacteroides ratio could be used as a predictive tool for weight loss trajectory. Early after surgery, patients who experienced successful weight loss showed an enrichment in taxa related to beneficial effects on host metabolism.
Emergency General Surgery Transfer and Effect on Inpatient Mortality and Post-Discharge Emergency Department Visits: A Propensity Score Matched Analysis
Authors: Watson Michael , Zhao Jing , Turk Philip , Hetherington Timothy , Schiffern Lynnette , Ross Samuel W , Matthews Brent D , Reinke Caroline E
Published: April 2022

BACKGROUND:

Patients undergoing emergency general surgery (EGS) and interhospital transfer (IHT) have increased mortality. Prior analyses of IHT have been limited by the inability to track post-discharge outcomes or have not included nonoperative EGS. We evaluated outcomes for IHT to our tertiary care facility compared with direct admission through the emergency department.

STUDY DESIGN:

Patients admitted directly (2015 to 2017) with a common EGS diagnosis (appendicitis, cholecystitis, choledocholithiasis, small bowel obstruction, and diverticulitis) were propensity score matched to patients transferred from another acute care hospital. Propensity score matching (PSM) was performed using patient characteristics, EGS diagnosis, comorbidities, and surgical critical care consultation. The primary outcome was inpatient mortality, and secondary outcomes were length of stay (LOS) 30-day hospital readmission.

RESULTS:

We identified 3,153 directly admitted patients and 1,272 IHT patients. IHT patients were older (mean 59.4 vs 51.5 years), had a higher Charlson comorbidity index (median 3 vs 1), White race (72% vs 49%), and BMI greater than 40 kg/m2 (11.6% vs 9.8%). After PSM, each group included 1,033 patients. IHT patients had a higher median LOS (5.5 days vs 3.8, p < 0.001), higher inpatient mortality (odds ratio [OR] 1.69, p = 0.03), and more complications (OR 1.57, p < 0.001). The rate of post-discharge 30-day hospital encounters was similar (OR 1.08, p = 0.460). However, IHT patients had more emergency department encounters (OR 1.35, p = 0.04) and fewer observation-status readmissions (OR 0.53, p = 0.01).

CONCLUSIONS:

After PSM to reduce confounding variables, patients with common EGS diagnoses transferred to a tertiary care facility have increased inpatient morbidity and mortality. The increased morbidity and resource utilization for these patients extends beyond the index hospital stay.
Cycle dynamics and synchronization in a coupled network of peripheral circadian clocks
Authors: Burckard Odile , Teboul Michèle , Delaunay Franck , Chaves Madalena
Published: April 2022

The intercellular interactions between peripheral circadian clocks, located in tissues and organs other than the suprachiasmatic nuclei of the hypothalamus, are still very poorly understood. We propose a theoretical and computational study of the coupling between two or more clocks, using a calibrated, reduced model of the circadian clock to describe some synchronization properties between peripheral cellular clocks. Based on a piecewise linearization of the dynamics of the mutual CLOCK:BMAL1/PER:CRY inactivation term, we suggest a segmentation of the circadian cycle into six stages, to help analyse different types of synchronization between two clocks, including single stage duration, total period and maximal amplitudes. Finally, our model reproduces some recent experimental results on the effects of different regimes of time-restricted feeding in liver circadian clocks of mice.
Time-keeping and decision-making in living cells: Part I
Authors: Tyson John J. , Csikasz-Nagy Attila , Gonze Didier , Kim Jae Kyoung , Santos Silvia , Wolf Jana
Published: April 2022

To survive and reproduce, a cell must process information from its environment and its own internal state and respond accordingly, in terms of metabolic activity, gene expression, movement, growth, division and differentiation. These signal–response decisions are made by complex networks of interacting genes and proteins, which function as biochemical switches and clocks, and other recognizable information-processing circuitry. This theme issue of
Interface Focus
(in two parts) brings together articles on time-keeping and decision-making in living cells—work that uses precise mathematical modelling of underlying molecular regulatory networks to understand important features of cell physiology. Part I focuses on time-keeping: mechanisms and dynamics of biological oscillators and modes of synchronization and entrainment of oscillators, with special attention to circadian clocks.
Persistent racial disparities in deep brain stimulation for Parkinson’s disease
Authors: Cramer Samuel W. , Do Truong H. , Palzer Elise F. , Naik Anant , Rice Abigail L. , Novy Savannah G. , Hanson Jacob T. , Piazza Amber N. , Howard Madeleine A. , Huling Jared D. , Chen Clark C. , McGovern Robert A.
Published: April 2022

We sought to determine whether racial and socio-economic disparities in the utilization of deep brain stimulation (DBS) for Parkinson’s disease (PD) have improved over time. We examined DBS utilization and analyzed factors associated with placement of DBS. The odds of DBS placement increased across the study period while White PD patients were 5 times more likely than Black patients to undergo DBS. Individuals, regardless of racial background, with two or more comorbidities were 14 times less likely to undergo DBS. Privately insured patients were 1.6 times more likely to undergo DBS. Despite increasing DBS utilization, significant disparities persist in access to DBS.
Semi-automated socio-anthropologic analysis of themedical discourseon rheumatoid arthritis: potential impact in public health
Authors: Nardini Christine , Candelise Lucia , Turrini Mauro , Addimanda Olga
Published: April 2022

The debilitating effects of non-communicable diseases (NCDs) and the accompanying chronic inflammation, represent a significant obstacle for the sustainability of our development, with efforts being spread worldwide to contrast NCDs’ diffusion, as per the United Nations Sustainable Development Goals (SDG 3). In fact, despite efforts of variable intensities in numerous directions (from innovations in biotechnology to lifestyle modifications), NCDs’ incidence remains pandemic.

The present work wants to contribute to this major concern with a specific focus on the fragmentation of the medical approaches, via an interdisciplinary analysis of themedical discourse, i.e. the heterogenous reporting that biomedical scientific literature uses to describe the anti-inflammatory therapeutic landscape in NCDs. The aim is to better capture the roots of this compartmentalization and the power relations existing among three segregatedpharmacological, experimentalandunstandardizedbiomedical approaches, to ultimately empower collaboration beyond medical specialties and possibly untap a more ample and effective reservoir of integrated therapeutic opportunities.

Using as exemplar disease rheumatoid arthritis (RA), twenty-eight articles were manually translated each into a nine-dimensional categorical variable of medical socio-anthropological relevance, relating in particular (but not only) tolegitimacy, temporalityandspatialization. This digitalized picture (9 × 28 table) of the medical discourse was further analyzed by simple automatic learning approaches to identify differences and highlight commonalities among the biomedical categories.

Interpretation of these results gives original insights including the suggestion to: empower scientific communication betweenunstandardizedapproaches and basic biology; promote non-pharmacological therapies repurposing to enhance robustness ofexperimentalapproaches; align the spatial representation of diseases and therapies inpharmacologyto effectively embrace thesystemicapproach promoted by modern personalized and preventive medicines. We hope this original work may expand and foster interdisciplinarity among public health stakeholders, ultimately contributing to the achievement of SGD3.
Privacy Risks of Whole-Slide Image Sharing in Digital Pathology
Authors: Holub Petr , Müller Heimo , Bíl Tomáš , Pireddu Luca , Plass Markus , Prasser Fabian , Schlünder Irene , Zatloukal Kurt , Nenutil Rudolf , Brázdil Tomáš
Published: April 2022

Access to large volumes of so-calledwhole-slide images—high-resolution scans of complete pathological slides—has become a cornerstone of the development of novel artificial intelligence methods in pathology for diagnostic use, education/training of pathologists, and research. Nevertheless, a methodology based on risk analysis for evaluating the privacy risks associated with sharing such imaging data and applying the principle “as open as possible and as closed as necessary” is still lacking. In this article, we develop a model for privacy risk analysis for whole-slide images which focuses primarily on identity disclosure attacks, as these are the most important from a regulatory perspective. We introduce a mathematical model for risk assessment and design a taxonomy of whole-slide images with respect to privacy risks. Based on this risk assessment model and the taxonomy, we conduct a series of experiments to demonstrate the risks using real-world imaging data. Finally, we develop guidelines for risk assessment and recommendations for low-risk sharing of whole-slide image data.
Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injury
Authors: Sedej Ivana , Štalekar Maja , Tušek Žnidarič Magda , Goričar Katja , Kojc Nika , Kogovšek Polona , Dolžan Vita , Arnol Miha , Lenassi Metka
Published: April 2022

Extracellular vesicle-bound DNA (evDNA) is an understudied extracellular vesicle (EV) cargo, particularly in cancer-unrelated fundamental and biomarker research. Although evDNA has been detected in urine, little is known about its characteristics, localization, and biomarker potential for kidney pathologies. To address this, we enriched EVs from urine of well-characterized kidney transplant recipients undergoing allograft biopsy, characterized their evDNA and its association to allograft injury. Using DNase treatment and immunogold labelling TEM, we show that DNA is bound to the surface of urinary EVs. Although the urinary evDNA and cell-free DNA correlated in several characteristics, the DNA integrity index showed evDNA was less fragmented (P< 0.001). Urinary EVs from patients with rejection and non-rejection allograft injury were significantly larger (mean:P= 0.045, median:P= 0.031) and have bound more DNA as measured by normalized evDNA yield (P= 0.018) and evDNA copy number (P= 0.007), compared to patients with normal histology. Urinary evDNA characteristics associated with the degree of interstitial inflammation, combined glomerulitis and peritubular capillaritis, and inflammation in areas of fibrosis (allP< 0.050). The normalized dd-evDNA copy numbers differed between the antibody- and T cell-mediated rejection (P= 0.036). Our study supports the importance of DNA as urine EV cargo, especially as potential non-invasive kidney allograft injury biomarker.
Health Economic Burden of COVID-19 in Saudi Arabia
Authors: Alenzi Khalidah A. , Al-malky Hamdan S. , Altebainawi Ali F. , Abushomi Hamidah Q. , Alatawi Fahad O. , Atwadi Moosa H. , Khobrani Moosa A. , Almazrou Dlal A. , Alrubeh Nariman , Alsoliabi Zainab A. , Kardam Abdulaziz M. , Alghamdi Shakr A. , Alasiri Abdulrahman , Alshammari Thamir M.
Published: April 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has placed a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19.

Methods

A retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across ten institutions in eight different regions in Saudi Arabia. The study calculated the estimated costs of all cases during the study period by using direct medical costs. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care.

Results

A total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male. Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.26 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were 14,585,640 SAR and 90,776,250 SAR, respectively. The total laboratory investigations ranked as the highest-cost services (22,086,296 SAR), followed by treatment (14,574,233.1 SAR). Overall, the total cost of all medical services for patients hospitalized with COVID-19 was 193,394,103.1 SAR.

Conclusion

This national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.

Key points

The nursing costs and length of stay were lower in the ICU than in the general ward.

The costs of hospitalization in general medical wards were less than those of admission to the ICU.

These cost data will be valuable for future researchers evaluating the COVID-19 pandemic’s increasing health care economic burden in Saudi Arabia and the implementation of cost-effective models to assess the possible implications of COVID-19 prevention and treatment initiatives.
Racial differences in white matter hyperintensity burden in aging, MCI, and AD
Authors: Morrison Cassandra , Dadar Mahsa , Manera Ana L. , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

White matter hyperintensities may be one of the earliest pathological changes in aging and may potentially accelerate cognitive decline. Whether race influences WMH burden has been conflicting. The goal of this study was to examine if race differences exist in WMH burden and whether these differences are influenced by vascular factors [i.e., diabetes, hypertension, body mass index (BMI)]. Participants from the Alzheimer’s Disease Neuroimaging Initiative were included if they had a baseline MRI, diagnosis, and WMH measurements. Ninety-one Black and 1937 White individuals were included. Using bootstrap re-sampling, 91 Whites were randomly sampled and matched to Black participants based on age, sex, education, and diagnosis 1000 times. Linear regression models examined the influence of race on baseline WMHs with and without vascular factors: WMH ∼ Race + Age + Sex + Education + BMI + Hypertension + Diabetes and WMH ∼ Race + Age + Sex + Education. The 95% confidence limits of the t-statistics distributions for the 1000 samples were examined to determine statistical significance. All vascular risk factors had significantly higher prevalence in Black than White individuals. When not including vascular risk factors, Black individuals had greater WMH volume overall as well as in frontal and parietal regions, compared to White individuals. After controlling for vascular risk factors, no WMH group differences remained significant. These findings suggest that vascular risk factors are a major contributor to racial group differences observed in WMHs.
White matter hyperintensity load varies depending on subjective cognitive decline criteria
Authors: Morrison Cassandra , Dadar Mahsa , Villeneuve Sylvia , Ducharme Simon , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

Background

Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD+) and without subjective cognitive decline (SCD–) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD+ and SCD-.

Methods

A total of 535 cognitively unimpaired older adults with 1353 time points from the Alzheimer’s Disease Neuroimaging Initiative were included in this study. SCD was operationalized using four different methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog+Worry, and Worry. Linear mixed-effects models were used to investigate the associations between SCD and overall and regional WMH burden.

Results

Overall temporal WMH burden differences were only observed with the Worry questionnaire. Higher WMH burden change over time was observed in SCD+ compared to SCD– in the temporal and parietal regions using the CCI (temporal, p=.01; parietal p=.03) and ECog (temporal, p=.03; parietal p=.01). For both the ECog+Worry and Worry questionnaire, change in WMH burden over time was increased in SCD+ compared to SCD- for overall, frontal, temporal, and parietal WMH burden (p<.05).

Conclusion

These results show that WMH burden differs between SCD+ and SCD– depending on the questionnaire and the approach (regional/global) used to measure WMHs. The various methods used to define SCD may reflect different types of underlying pathologies.
Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing?
Authors: Campbell Cori , Wang Tingyan , Burrow Rebekah , Mandal Sema , Hippisley-Cox Julia , Barnes Eleanor , Matthews Philippa C
Published: April 2022

Background

HBV is the leading global cause of cirrhosis and primary liver cancer. The virus’s attributable disease burden in the UK is concentrated in vulnerable populatons including ethinic minorities, people experiencing homelessness and people born in high-prevalence countries. Despite this the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or positivity rate vary widely across sources. We summarised datasets that are available to represent UK CHB epidemiology, consider differences between sources, and discuss deficiencies in current estimates.

Methods

We searched for estimates of CHB case numbers in the UK (incorporating incidence and/or prevalence-like data) across a range of available sources, including UK-wide reports from government bodies, publications from independent bodies (including medical charities and non-governmental organisations) and articles in peer-reviewed scientific journals. We present positivity rates from each respective data source but caution that estimates may not be representative of the true UK-wide population prevalence.

Results and Discussion

Six CHB case number estimates were identified, with three estimates reporting information concerning population subgroups, including number of infected individuals across age, sex and ethnicity categories., Estimates among sources reporting prevalence varied from 0.27% to 0.73%. An alterantive proxy for population prevalence (obtained via the UK antenatal screening programme which achieves over 95% coverage of every pregnant woman) estimated a CHB prevalence of <0.5%. Estimates varied by sources of error, bias and missingness, data linkage, and substantial “blind spots” in consistent testing and registration of HBV diagnoses. Multi-parameter evidence synthesis and back-calculation model methods similar to those used to generate estimates of HCV ad HIV population-wide prevalence may be applicable to HBV.
Protection conferred by vaccine plus previous infection (hybrid immunity) with vaccines of three different platforms during the Omicron variant period in Brazil
Authors: Cerqueira-Silva Thiago , de Araujo Oliveira Vinicius , Paixão Enny S. , Veras Florentino Pilar Tavares , Penna Gerson O. , Pearce Neil , Werneck Guilherme L. , Barreto Maurício L. , Boaventura Viviane S. , Barral-Netto Manoel
Published: April 2022

Hybrid immunity (infection plus vaccination) provided high protection against infection and severe disease in the periods of delta and gamma variants of concern. However, the protection of hybrid immunity in the Omicron era remains unknown. We performed a test-negative study using Brazilian national databases between January 01 and March 22, 2022, a period of predominant circulation of the Omicron variant in Brazil. Hybrid immunity offered low protection against infection, with rapid waning, compared to unvaccinated with or without previous infection. For severe illness (hospitalisation or death), the protection, although already high for unvaccinated pre-infected increased regardless of the type of vaccine (Ad26.COV2.S, BNT162b2, ChAdOx-1 or CoronaVac).

In conclusion, during the Omicron-dominant period in Brazil, hybrid immunity offered high protection against severe illness and low protection against infection.
Radioactive Contamination in Feral Dogs in the Chernobyl Exclusion Zone: Population Body-Burden Survey and Implications for Human Radiation Exposure
Authors: Hecla Jake , Kambarian Erik , Tubbs Robert , McKinley Carla , Berliner Aaron J. , Russell Kayla , Spatola Gabrielle , Chertok Jordan , Braun Weston , Hank Natalia , Marquette Courtney , Betz Jennifer , Paik Terry , Chenery Marie , Cagan Alex , Willis Carl , Mousseau Tim
Published: April 2022

This report describes a two-year effort to survey the internal 137Cs and external β-emitter contamination present in the feral dog population near the Chernobyl nuclear power plant (ChNPP) site, and to quantify the potential for human radiation exposure from this contamination. This work was performed as an integral part of the radiation safety and control procedures of an animal welfare oriented trap-neuter-release (TNR) program. The measurement program employed handheld β-sensitive probes, and a simple whole-body counter to measure internal 137Cs burden during post-surgical observation and recovery. External β contamination surveys performed during intake showed that 21/288 animals had significant, removable external contamination. Measurements with the whole-body counter indicated internal 137Cs body burdens ranging from undetectable (minimum detection level ∼100 Bq/kg in 2017, ∼ 30 Bq/kg in 2018) to approximately 30,000 Bq/kg. A total of 33 animals had 137Cs body-burdens above 1 kBq/kg. We observe that internal contamination levels are positively correlated with capture locations within ChNPP boundaries. The large variation in the 137Cs concentration in these animals is not well-understood, could be due to prey selection, access to human food scraps, or extended residence in highly contaminated areas. These internally-contaminated animals are unlikely to pose an exposure hazard despite their large body-burdens due to their limited exposure to humans. However, the small minority of animals with external contamination may pose a contamination hazard to workers, tourists, and others interacting with the dogs, as evidenced by total quantity of removable activity and incidents of transfer to materials used in animal capture.
Conserved cell-type specific signature of resilience to Alzheimer’s disease nominates role for excitatory intratelencephalic cortical neurons
Authors: Telpoukhovskaia Maria A. , Hadad Niran , Gurdon Brianna , Dai Yanchao , Ouellette Andrew R. , Neuner Sarah M. , Dunn Amy R. , Willcox Jon A. L. , Wu Yiyang , Dumitrescu Logan , Bellur Orhan , Zhang Ji-Gang , O’Connell Kristen M.S. , Dammer Eric B. , Seyfried Nicholas T. , Muzumdar Sukalp , Gillis Jesse , Robson Paul , Arnold Matthias , Hohman Timothy J. , Philip Vivek M. , Menon Vilas , Kaczorowski Catherine C.
Published: April 2022

Alzheimer’s disease (AD), the leading cause of dementia, affects millions of people worldwide. With no disease-modifying medication currently available, the human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline and pathology (amyloid plaques and neurofibrillary tangles) are present. Remarkably, some individuals who have AD pathology remain cognitively normal. Uncovering factors that lead to “cognitive resilience” to AD is a promising path to create new targets for therapies. However, technical challenges discovering novel human resilience factors limit testing, validation, and nomination of novel drugs for AD. In this study, we use single-nucleus transcriptional profiles of postmortem cortex from human individuals with high AD pathology who were either cognitively normal (resilient) or cognitively impaired (susceptible) at time of death, as well as mouse strains that parallel these differences in cognition with high amyloid load. Our cross-species discovery approach highlights a novel role for excitatory layer 4/5 cortical neurons in promoting cognitive resilience to AD, and nominates several resilience genes that includeATP1A1,GRIA3,KCNMA1, andSTXBP1. This putative cell type has been implicated in resilience in previous studies on bulk RNA-seq tissue, but our single-nucleus and cross-species approach identifies particular resilience-associated gene signatures in these cells. These novel resilience candidate genes were tested for replication in orthogonal data sets and confirmed to be correlated with cognitive resilience. Based on these gene signatures, we identified several potential mechanisms of resilience, including regulation of synaptic plasticity, axonal and dendritic development, and neurite vesicle transport along microtubules that are potentially targetable by available therapeutics. Because our discovery of resilience-associated genes in layer 4/5 cortical neurons originates from an integrated human and mouse transcriptomic space from susceptible and resilient individuals, we are positioned to test causality and perform mechanistic, validation, and pre-clinical studies in our human-relevant AD-BXD mouse panel.
Microglia undergo rapid phenotypic transformation in acute brain slices but remain essential for neuronal synchrony
Authors: Berki Péter , Cserép Csaba , Pósfai Balázs , Szabadits Eszter , Környei Zsuzsanna , Kellermayer Anna , Nyerges Miklós , Wei Xiaofei , Mody Istvan , Araki Kunihiko , Beck Heinz , He Kaikai , Wang Ya , Wu Zhaofa , Jing Miao , Li Yulong , Gulyás Attila I. , Dénes Ádám
Published: April 2022

Acute brain slices represent a “workhorse” model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue injury, it is unclear how microglia, the main immune cells and damage sensors of the CNS shape tissue integrityex vivo. To this end, we have studied the mechanisms of microglial phenotype changes and contribution to neuronal network organisation and functioning in acute brain slices. Using a novel ATP- reporter mouse line and microglia reporter mice, we show that acute slice preparation induces rapid, P2Y12 receptor (P2Y12R) dependent dislocation and migration of microglia, paralleled with marked morphological transformations driven by early ATP surges and subsequent ATP flashes. Gradual depolarization of microglia is associated with the downregulation of purinergic P2Y12R and time-dependent changes of microglia-neuron interactions, paralleled by altered numbers of excitatory and inhibitory synapses. Importantly, functional microglia not only modulate synapse sprouting, but the absence of microglia or microglial P2Y12R markedly diminishes the incidence, amplitude, and frequency of sharp wave-ripple activity in hippocampal slices. Collectively, our data suggest that microglia are inherent modulators of complex neuronal networks, and their specific actions are indispensable to maintain neuronal network integrity and activityex vivo.These findings could facilitate new lines of research resulting in improvedex vivomethodologies and a better understanding of microglia-neuron interactions both in physiological and pathological conditions.
Validation of genetic variants from NGS data using Deep Convolutional Neural Networks
Authors: Vaisband Marc , Schubert Maria , Gassner Franz Josef , Geisberger Roland , Greil Richard , Zaborsky Nadja , Hasenauer Jan
Published: April 2022

Accurate somatic variant calling from next-generation sequencing data is one most important tasks in personalised cancer therapy. The sophistication of the available technologies is ever-increasing, yet, manual candidate refinement is still a necessary step in state-of-the-art processing pipelines. This limits reproducibility and introduces a bottleneck with respect to scalability. We demonstrate that the validation of genetic variants can be improved using a machine learning approach resting on a Convolutional Neural Network, trained using existing human annotation. In contrast to existing approaches, we introduce a way in which contextual data from sequencing tracks can be included into the automated assessment. A rigorous evaluation shows that the resulting model is robust and performs on par with trained researchers following published standard operating procedure.
Systematic conformation-to-phenotype mapping via limited deep-sequencing of proteins
Authors: Serebryany Eugene , Zhao Victor Y. , Park Kibum , Bitran Amir , Trauger Sunia A. , Budnik Bogdan , Shakhnovich Eugene I.
Published: April 2022

Non-native conformations drive protein misfolding diseases, complicate bioengineering efforts, and fuel molecular evolution. No current experimental technique is well-suited for elucidating them and their phenotypic effects. Especially intractable are the transient conformations populated by intrinsically disordered proteins. We describe an approach to systematically discover, stabilize, and purify native and non-native conformations, generatedin vitroorin vivo, and directly link conformations to molecular, organismal, or evolutionary phenotypes. This approach involves high-throughput disulfide scanning (HTDS) of the entire protein. To reveal which disulfides trap which chromatographically resolvable conformers, we devised a deep-sequencing method for double-Cys variant libraries of proteins that precisely and simultaneously locates both Cys residues within each polypeptide. HTDS of the abundantE. coliperiplasmic chaperone HdeA revealed distinct classes of disordered hydrophobic conformers with variable cytotoxicity depending on where the backbone was cross-linked. HTDS can bridge conformational and phenotypic landscapes for many proteins that function in disulfide-permissive environments.
Estimation of Left Ventricular Mechanical Activation Times from Motion-Corrected Cardiac 4DCT Images
Authors: Manohar Ashish , Yang James , Pack Jed D. , McVeigh Elliot R.
Published: April 2022

Background

Mechanical activation times of the left ventricle (LV) are strongly correlated with patient response to cardiac resynchronization therapy (CRT); however, there remains an unmet clinical need for a simple, robust imaging modality that yields accurate and reproducible estimates of LV mechanical activation times. Modern four-dimensional computed tomography (4DCT) imaging systems with effective motion correction could fulfill this need.

Purpose

To demonstrate the clinical utility of a newly developed cardiac motion correction algorithm called ResyncCT and to investigate its effect on estimating mechanical activation times of the LV.

Methods

Twenty-four subjects with full cardiac volume, full cardiac cycle 4DCT images were retrospectively analyzed in this study. The reconstructed 4DCT images exhibited typical motion artifact characteristics that were dependent on the direction of LV wall motion with respect to the gantry position at each cardiac phase; these artifacts rotated synchronously with the gantry. The motion corrupted images, referred to as the uncorrected images, were processed with a novel cardiac motion correction algorithm called ResyncCT to yield motion corrected images (referred to as the ResyncCT images). Regional shortening (RSCT) of the LV was calculated over a 72-segment model for both the uncorrected and the ResyncCT images; each segment contained RSCT vs time data. From these RSCT vs time curves, LV mechanical activation was estimated as the time point at which the RSCT vs time curve shortened by 10% of its full dynamic range during systolic contraction; we refer to this time point as the time to onset of shortening (TOS). A shift in TOS > |35| ms has a significant effect on reclassifying patients based on their probabilities of responding to CRT; we investigated the effect of ResyncCT on the measured values of TOS over the LV.

Results

ResyncCT had a pronounced effect on the TOS estimates; ResyncCT could potentially reclassify 23/24 (96%) subjects as either responders or non-responders to CRT. In 16/24 (67%) subjects, the differences in TOS that were sufficient to bring about a reclassification of CRT response were at least as large in surface area of the LV as one entire American Heart Association segment.

Conclusions

We demonstrated the clinical utility of ResyncCT in estimating LV mechanical activation times as ‘times to onset of shortening’ in 24 human subjects. ResyncCT has a pronounced effect on the estimation of LV mechanical activation times; the differences in activation times between the ResyncCT and uncorrected images are heterogenous and subject specific. The effect of ResyncCT could potentially reclassify 96% of the subjects used in this study based on their probabilities of responding to CRT. The results reported in this study highlight the potential utility of ResyncCT in estimating timing of mechanical events of interest of the LV for CRT planning.
Nav1.2 and BK channels interaction shapes the action potential in the axon initial segment
Authors: Filipis Luiza , Blömer Laila Ananda , Montnach Jérôme , De Waard Michel , Canepari Marco
Published: April 2022

In neocortical layer-5 pyramidal neurons, the action potential (AP) is generated in the axon initial segment (AIS) when the membrane potential (Vm) reaches the threshold for activation of two diverse voltage-gated Na+ channels, that differ in spatial distribution and biophysical properties. Yet, the understanding of specific functional differences between these two channels remains elusive. Here, using ultrafast Na+, Vm and Ca2+ imaging in combination with partial block of Nav1.2 by a recent peptide, we demonstrate an exclusive role of Nav1.2 in shaping the generating AP. Precisely, Ca2+ influx via Nav1.2 activates BK Ca2+-activated K+ channels determining the amplitude and the early phase of repolarisation of the AP in the AIS. We mimicked this result with a NEURON model where the role of the different ion channels tested reproduced the experimental evidence. The exclusive role of Nav1.2 reported here is important for understanding the physiology and pathology of neuronal excitability.