bluuebunny/crossref_metadata_2025 huggingface dataset:
Disengagement From HIV Care and Failure of Second-Line Therapy in Nigeria: A Retrospective Cohort Study, 2005–2017
Authors: El Bouzidi Kate , Murtala-Ibrahim Fati , Kwaghe Vivian , Datir Rawlings P. , Ogbanufe Obinna , Crowell Trevor A. , Charurat Man , Dakum Patrick , Gupta Ravindra K. , Ndembi Nicaise , Sabin Caroline A.
Published: January 2022

Background:

Understanding the correlates of disengagement from HIV care and treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve clinical outcomes among people living with HIV (PLHIV).

Methods:

We conducted a retrospective cohort study of PLHIV aged >15 years who started second-line ART at a tertiary center in Nigeria between 2005 and 2017. Participants were considered to have disengaged from care if they had not returned within a year after each clinic visit. Cox proportional hazard models were used to investigate factors associated with: (1) viral failure (HIV-1 RNA >1000 copies/mL), (2) immunologic failure (CD4 count decrease or <100 cells/mm3), and (3) severe weight loss (>10% of bodyweight), after >6 months of second-line ART.

Results:

Among 1031 participants, 33% (341) disengaged from care during a median follow-up of 6.9 years (interquartile range 3.7–8.5). Of these, 26% (89/341) subsequently reentered care. Disengagement was associated with male gender, age <30 years, lower education level, and low CD4 count at second-line ART initiation. Among participants with endpoint assessments available, 20% (112/565) experienced viral failure, 32% (257/809) experienced immunologic failure, and 23% (190/831) experienced weight loss. A lower risk of viral failure was associated with professional occupations compared with elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04 to 0.70).

Conclusion:

Adverse outcomes were common during second-line ART. However, reengagement is possible and resources should be allocated to focus on retaining PLHIV in care and providing services to trace and reengage those who have disengaged from care.
Cost-Effectiveness of Interventions to Improve HIV Pre-exposure Prophylaxis Initiation, Adherence, and Persistence Among Men Who Have Sex With Men
Authors: Wheatley Margo M. , Knowlton Gregory , Kao Szu-Yu , Jenness Samuel M. , Enns Eva A.
Published: January 2022

Background:

To help achieve Ending the HIV Epidemic (EHE) goals of reducing new HIV incidence, pre-exposure prophylaxis (PrEP) use and engagement must increase despite multidimensional barriers to scale-up and limitations in funding. We investigated the cost-effectiveness of interventions spanning the PrEP continuum of care.

Setting:

Men who have sex with men in Atlanta, GA, a focal jurisdiction for the EHE plan.

Methods:

Using a network-based HIV transmission model, we simulated lifetime costs, quality-adjusted life years (QALYs), and infections averted for 8 intervention strategies using a health sector perspective. Strategies included a status quo (no interventions), 3 distinct interventions (targeting PrEP initiation, adherence, or persistence), and all possible intervention combinations. Cost-effectiveness was evaluated incrementally using a $100,000/QALY gained threshold. We performed sensitivity analyses on PrEP costs, intervention costs, and intervention coverage.

Results:

Strategies averted 0.2%–4.2% new infections and gained 0.0045%–0.24% QALYs compared with the status quo. Initiation strategies achieved 20%–23% PrEP coverage (up from 15% with no interventions) and moderate clinical benefits at a high cost, while adherence strategies were relatively low cost and low benefit. Under our assumptions, the adherence and initiation combination strategy was cost-effective ($86,927/QALY gained). Sensitivity analyses showed no strategies were cost-effective when intervention costs increased by 60% and the strategy combining all 3 interventions was cost-effective when PrEP costs decreased to $1000/month.

Conclusion:

PrEP initiation interventions achieved moderate public health gains and could be cost-effective. However, substantial financial resources would be needed to improve the PrEP care continuum toward meeting EHE goals.
Higher Cerebrospinal Fluid Soluble Urokinase-type Plasminogen Activator Receptor, But Not Interferon γ-inducible Protein 10, Correlate With Higher Working Memory Deficits
Authors: De Almeida Sergio M. , Rotta Indianara , Tang Bin , Umlauf Anya , Vaida Florin , Cherner Mariana , Franklin Donald , Letendre Scott , Ellis Ronald J. ,   the HNRC Group
Published: January 2022

Background:

We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S).

Methods:

A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and β2 microglobulin (β2m) in the CSF and serum were quantified using different immunoassays.

Results:

Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum β2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and β2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum β2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024).

Discussion:

We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.
An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE)
Authors: Elliott Jessie A. , Markar Sheraz R. , Klevebro Fredrik , Johar Asif , Goense Lucas , Lagergren Pernilla , Zaninotto Giovanni , van Hillegersberg Richard , van Berge Henegouwen Mark I. , Nilsson Magnus , Hanna George B. , Reynolds John V. ,   ENSURE Study Group
Published: January 2022

Objective:

To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer.

Summary Background Data:

Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence.

Methods:

European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009–2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed.

Results:

Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12–0.25]) and increased tumor-directed therapy (OR 2.09 [1.58–2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89–1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47–0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58–0.89]). IS was associated with greater anxiety (P =0.016), but similar overall HRQL.

Conclusions:

IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.
Postoperative and Pathological Outcomes of CROSS and FLOT as Neoadjuvant Therapy for Esophageal and Junctional Adenocarcinoma
Authors:   Oesophago-Gastric Anastomotic Audit (OGAA) Collaborative
Published: January 2022

Objective:

This study aimed to compare the postoperative and pathological outcomes between carboplatin, paclitaxel, radiotherapy (CROSS) and 5-FU, leucovorine, oxaliplatin and docetaxel (FLOT) in esophageal adenocarcinoma (EAC) patients from an international, multicenter cohort.

Summary of Background Data:

Ongoing debate exists around optimum approach to locally advanced EAC, with proponents for perioperative chemotherapy, such as FLOT, or multimodal therapy, in particular the CROSS regimen.

Methods:

Patients undergoing CROSS (n = 350) and FLOT (n = 368), followed by curative esophagectomy for EAC were identified from the Oesophagogastric Anastomosis Audit.

Results:

The 90-day mortality was higher after CROSS than FLOT (5% vs 1%, P = 0.005), even on adjusted analyses [odds ratio (OR): 3.97, confidence interval (CI)95%: 1.34–13.67]. Postoperative mortality in CROSS were related to higher pulmonary (74% vs 60%) and cardiac complications (42% vs 20%) compared to FLOT. CROSS was associated with higher pathologic complete response (pCR) rates (18% vs 10%, P = 0.004) and margin-negative resections (93% vs 76%, P < 0.001) compared with FLOT. On adjusted analyses, CROSS was associated with higher pCR rates (OR: 2.05, CI95%: 1.26-3.34) and margin-negative resections (OR: 4.55, CI95%: 2.70-7.69) compared to FLOT.

Conclusions:

This study provides real-world data CROSS was associated with higher 90-day mortality than FLOT, related to cardio-pulmonary complications with CROSS. These warrant a further review into causes and mechanisms in selected patients, and at minimum suggest the need for strict radiation therapy quality assurance. Research into impact of higher pCR rates and R0 resections with CROSS compared to FLOT on long-term survival is needed.
The Relationship Between Decision-making Capacity and the Domains of Awareness in Alzheimer Disease
Authors: de Souza Natalie A.P. , de Oliveira Felipe , de Carvalho Raquel L.S. , Dourado Marcia C.N.
Published: January 2022

People with Alzheimer dementia (PwAD) who are aware of their overall cognitive function and diagnosis are more likely to be judged competent in decision-making capacity. Therefore, we aimed to investigate the relationship between decision-making capacity and the different domains of awareness and the relationship between decision-making capacity and the cognitive and clinical impairment of the PwAD. Using a cross-sectional design, we included 121 PwAD and their caregivers. Awareness was assessed across domains, including cognitive functioning and health condition, functional activity impairments, emotional state, social functioning, and interpersonal relationships. The MacArthur Competence Assessment Tool for Treatment was adopted to gather information about decision-making abilities. We found that decision-making capacity is related to the cognitive and functional domains of awareness and relatively independent of the emotional functioning and the relationship domains. Our finding highlighted that PwAD who are unaware of the disease or the cognitive and functional impairments might be unlikely to appreciate the personal benefits of a proposed health treatment or to understand and judge the personal consequences of a decision accurately.
Association Between Adherence to the MIND Diet and Cognitive Performance is Affected by Income
Authors: Ferreira Naomi V. , Lotufo Paulo A. , Marchioni Dirce M.L. , Barreto Sandhi M. , Viana Maria C. , Caramelli Paulo , Bensenor Isabela J.M. , Suemoto Claudia K.
Published: January 2022

Background:

The relationship between the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet and cognition has not been widely investigated in low- to middle-income countries. We investigated the relationship between MIND diet and cognition in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline data.

Methods:

We included 11,788 participants. MIND diet adherence was based on the intake of 15 components according to a food frequency questionnaire. We analyzed the association between MIND diet adherence and global cognition, memory, and executive function using adjusted linear regression. We examined the interaction between income and MIND diet adherence on cognition and presented income stratified analyses.

Results:

MIND diet adherence was not associated with cognition in the whole sample. Income was an effect modifier of MIND adherence on global cognition (P=0.03) and executive function (P<0.001). For participants with high income, greater adherence was associated with better executive function [β=0.015, 95% confidence interval (CI)=0.002; 0.028, P=0.025]; while for participants with low income, greater adherence was associated with lower global cognition (β=−0.020, 95% CI=−0.036; −0.005, P=0.010) and executive function (β=−0.023, 95% CI=−0.039; −0.007, P=0.004). Adherence to the MIND diet was higher among participants with high income (P<0.001).

Conclusion:

For high-income participants, greater adherence was associated with better cognitive performance; for low-income participants, greater adherence was associated with lower cognitive performance.
Whole Exome Sequencing (WES) identifies Homozygous mutation in g.37429732G>A in GRHPR gene is responsible for early onset of nephrolithiasis in the population of West Bengal, India
Authors: Chatterjee Arindam , Sarkar Kunal , Bank Sarbashri , Saraf Siddharth , wakle Dhansagar , pal Dilip Kumar , Chakraborty Santanu , Ghosh Sudakshina , bankura Biswabandhu , Das Madhusudan
Published: January 2022

Kidney stone disease (KSD) or nephrolithiasis (NL), is a serious clinical concern that gradually poses threat to global health and economy. The frequency of KSD is rapidly increasing and about 12% of the Indian population are suffering from this disease. In this scenario, we studied the incidence and age group stratification of KSD in the eastern part of India. Furthermore, patients with GRHPR mutation were highly predominant. Furthermore, real time quantitative PCR expression and protein expression through immunoblotting along with protein activity & computational analysis were carried out in patients with GRHPR mutation. Our findings revealed that the candidates of the early age group are prone to hyperoxaluria moreover a potent and frequent mutation in the GRHPR gene is widely present in this age group. Further, biochemical tests such as serum creatine, serum urea, serum and urinary calcium were carried out for the patients along with age matched controls. Moreover, the actual underlying cause of nephrolithiasis for lower age groups still remains unclear. The study revealed that mutations were more often found in GRHPR, AGXT, and HOGA1 genes in the study cohort.
Resveratrol increases tear production and spontaneous ocular pain after corneal abrasion in male, but not female, rats using a preclinical model of photorefractive keratectomy (PRK)
Authors: Hegarty Deborah M. , Carroll James R. , Nguyen Dennis , Halls Victoria S. , Robbins Dennis I. , Price Theodore J. , Dussor Gregory , Aicher Sue A.
Published: January 2022

Photorefractive keratectomy (PRK) is an alternative to LASIK and can cause intense acute pain that is often not relieved by standard treatments. To assess potential therapeutics for this type of acute pain, appropriate preclinical models are needed. Herein we describe a rodent preclinical model of PRK and a multi-faceted approach to determine the therapeutic potential of resveratrol, a natural phytoestrogen, on pain, tear production, and the corneal epithelium. Studies were conducted in male and female Sprague-Dawley rats. Heptanol was applied to one eye and the superficial corneal epithelium was removed, mimicking the abrasion seen in PRK. Spontaneous pain was assessed with orbital tightening (OT) scores for 7 days. Corneal abrasion increased OT scores in both male and female rats with peak responses at 24 - 48 hours. Topical application of resveratrol had a sex-specific effect on OT scores and tear production. Resveratrol increased OT scores in abraded males, but not females, at 72 hours and 1 week after abrasion. Resveratrol dose-dependently increased tear production in abraded males, but had no effect in abraded females. While there was no correlation between OT score at 1 week and tear production, CGRP content of corneal nerves was positively correlated with 1 week OT score. There was also a significant increase in CD68-labeled macrophages in resveratrol-treated abraded corneas as compared to naïve corneas. These findings demonstrate the usefulness of our preclinical PRK model for the assessment of ocular pain therapeutics and indicate that topical resveratrol may not be useful for managing PRK-induced pain.
DNA methylation and general psychopathology in childhood: An epigenome-wide meta-analysis from the PACE consortium
Authors: Rijlaarsdam Jolien , Cosin Marta , Schellhas Laura , Abrishamcar Sarina , Malmberg Anni , Neumann Alexander , Felix Janine F. , Sunyer Jordi , Gutzkow Kristine B. , Grazuleviciene Regina , Wright John , Kampouri Mariza , Zar Heather J. , Stein Dan J. , Heinonen Kati , Räikkönen Katri , Lahti Jari , Huels Anke , Caramaschi Doretta , Alemany Silvia , Cecil Charlotte A. M.
Published: January 2022

The general psychopathology factor (GPF) has been proposed as a way to capture variance shared between psychiatric symptoms. Despite a growing body of evidence showing both genetic and environmental influences on GPF, the biological mechanisms underlying these influences remain unclear. In the current study, we conducted epigenome-wide meta-analyses to identify both probe- and region-level associations of DNA methylation (DNAm) with school-age general psychopathology in six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was examined both at birth (cord blood; prospective analysis) and during school-age (peripheral whole blood; cross-sectional analysis) in total samples of N=2,178 and N=2,190, respectively. At school-age, we identified one probe (cg11945228) located in the Bromodomain-containing protein 2 gene (BRD2) that negatively associated with GPF (p=8.58×10−8). We also identified a significant DMR at school-age (p=1.63×10−8), implicating the SHC Adaptor Protein 4 (SHC4) gene that has been previously implicated in multiple types of psychiatric disorders in adulthood, including obsessive compulsive disorder and major depressive disorder. In contrast, no prospective associations were identified with DNAm at birth. Taken together, results of this study revealed some evidence of an association between DNAm at school-age and GPF. Future research with larger samples is needed to further assess DNAm variation associated with GPF.
Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study
Authors: Yegorov Sergey , Kadyrova Irina , Negmetzhanov Baurzhan , Kolesnikova Yevgeniya , Kolesnichenko Svetlana , Korshukov Ilya , Baiken Yeldar , Matkarimov Bakhyt , Miller Matthew S. , Hortelano Gonzalo H. , Babenko Dmitriy
Published: January 2022

Background

Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in >70 countries. Yet there is a shortage of data on this vaccine’s performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in a multiethnic cohort from Kazakhstan.

Methods

COVID-19-free participants (n=82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays.

Findings

Of the 73 and 70 participants retained post-dose 1 and 2, respectively, most (>50%) reported mild-to-moderate injection site or systemic reactions to vaccination; no severe or potentially life-threatening conditions were reported. dose 1 appeared to be more reactogenic than dose 2, with fatigue and headache more frequent in participants with prior COVID-19 exposure. After dose 2 nausea was more common in subjects without prior COVID-19. The combined S-IgG and S-IgA seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization titers was 83% post-dose 1’, and increased to 98% post-dose 2’, with the largest relative increase observed in participants without prior COVID-19 exposure. Nasal S-IgG and S-IgA increased post-dose 1, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count.

Interpretation

Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal, suggesting that adjustments to the current vaccine dosing regimen may be necessary to optimize immunization efficacy and cost-effectiveness. Although Sputnik-V appears to have a reactogenicity profile similar to that of other COVID-19 vaccines, the observed alterations to the GRO/platelet axis call for further investigation of Sputnik V effects on systemic immunology.

Funding

Ministry of Education and Science of the Republic of Kazakhstan.
Validation of diagnostic nomograms based on CE-MS urinary biomarkers to distinguish clinically significant prostate cancer
Authors: Frantzi Maria , Heidegger Isabel , Roesch Marie C. , Gomez-Gomez Enrique , Steiner Eberhard , Vlahou Antonia , Mullen William , Guler Ipek , Merseburger Axel S. , Mischak Harald , Culig Zoran
Published: January 2022

Background

Prostate cancer (PCa) is the most common cancer and one of the leading causes of death worldwide. However, a significant proportion of PCa are low risk PCa which do not require an active treatment due to its low mortality rates. Thus, one major issue in PCa management is to accurately distinguish between indolent and clinically significant (cs) PCa to reduce overdiagnosis and overtreatment. In this study, we aim to validate the performance of diagnostic nomograms (DN) based on previously published urinary biomarkers for discriminating csPCa.

Patients and Methods

Capillary electrophoresis/ mass spectrometry has been employed to validate a published biomarker model based on 19 urinary peptides specific for csPCa. Added value of the 19-biomarker model (19-BM) was assessed in diagnostic nomograms including prostate specific antigen (PSA), PSA density and the risk calculator from The European Randomized Study of Screening for Prostate Cancer (ERSPC). For this purpose, urine samples from 147 PCa patients (including 80 low, 44 intermediate and 17 high risk patients) were collected prior to prostate biopsy. The 19-BM score was calculated via a support vector machine-based software based on the pre-defined cut-off criterion of -0.07. DNs were subsequently developed to assess added value of integrative diagnostics.

Results

Independent validation of the 19-BM resulted in 87% sensitivity and 65% specificity, with an AUC of 0.81, outperforming PSA (AUCPSA:0.64), PSA density (AUCPSAD: 0.64) and ERSPC-3/4 risk calculator (0.67). Integration of 19-BM with the other clinical variables into distinct DN, resulted in improved (AUC range: 0.82-0.88) but not significantly better performance compared to 19-BM alone.

Conclusions

19-BM alone or combined with clinical variables into DN, demonstrated value for detecting csPCa, and decreasing the number of biopsies.
Causal Effects Contributing to Elevated Metabolic Power During Walking in Children Diagnosed with Cerebral Palsy
Authors: Gill Pavreet K. , Steele Katherine M. , Donelan J. Maxwell , Schwartz Michael H.
Published: January 2022

Metabolic power (net energy consumed while walking per unit time) is, on average, two-to-three times greater in children with cerebral palsy (CP) than their typically developing peers, contributing to greater physical fatigue, lower levels of physical activity and greater risk of cardiovascular disease. The goal of this project was to identify the total causal effects of clinical factors that may contribute to high metabolic power demand in children with CP.

We included children who 1) visited Gillette Children’s Specialty Healthcare for a quantitative gait assessment after the year 2000, 2) were formally diagnosed with CP, 3) were classified as level I-III under the Gross Motor Function Classification System and 4) were 18 years old or younger. We created a structural causal model that specified the assumed relationships of a child’s gait pattern (i.e., gait deviation index, GDI) and common impairments (i.e., dynamic and selective motor control, strength, and spasticity) with metabolic power. We estimated causal effects using Bayesian additive regression trees, adjusting for factors identified by the causal model.

There were 2157 children who met our criteria. We found that a child’s gait pattern, as summarized by the GDI, affected metabolic power approximately twice as much as the next largest contributor. Selective motor control, dynamic motor control, and spasticity had the next largest effects. Among the factors we considered, strength had the smallest effect on metabolic power.

Our results suggest that children with CP may benefit more from treatments that improve their gait pattern and motor control than treatments that improve spasticity or strength.
Germline TYK2 mutation and cancer risk
Authors: Yarmolinsky James , Amos Christopher I. , Hung Rayjean J. , Moreno Victor , Burrows Kimberley , Smith-Byrne Karl , Atkins Joshua R. , Brennan Paul ,   Colon Cancer Family Registry (CCFR),   Colorectal Cancer Transdisciplinary study (CORECT),   Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO),   Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium, McKay James D. , Martin Richard M. , Smith George Davey
Published: January 2022

Deucravacitinib, a novel, selective inhibitor of TYK2 is currently under review at the FDA and EMA for treatment of moderate-to-severe plaque psoriasis. It is unclear whether recent safety concerns (i.e. elevated rates of lung cancer and lymphoma) related to similar medications (i.e. other JAK inhibitors) are shared with this novel TYK2 inhibitor. We used a partial loss-of-function variant in TYK2 (rs34536443), previously shown to protect against psoriasis and other autoimmune diseases, to evaluate the potential effect of therapeutic TYK2 inhibition on risk of lung cancer and non-Hodgkin lymphoma. Summary genetic association data on lung cancer risk were obtained from a GWAS meta-analysis of 29,266 cases and 56,450 controls in the Integrative Analysis of Lung Cancer Risk and Etiology (INTEGRAL) consortium. Summary genetic association data on non-Hodgkin lymphoma risk were obtained from a GWAS meta-analysis of 8,489 cases and 374,506 controls in the UK Biobank and InterLymph consortium. In the primary analysis, each copy of the minor allele of rs34536443, representing partial TYK2 inhibition, was associated with an increased risk of lung cancer (OR 1.15, 95% CI 1.07-1.24, P = 1.72 × 10-4) and non-Hodgkin lymphoma (OR 1.18, 95% CI 1.05-1.33, P = 5.25 × 10-3). In secondary analyses, there was weak evidence of an association of rs34536443 with advanced prostate cancer risk (OR 1.08, 95% CI 1.00-1.17, P = 0.04), but little evidence of association with three other common adult cancers examined. Our analyses using an established partial loss-of-function mutation to mimic TYK2 inhibition provide genetic evidence that therapeutic TYK2 inhibition may increase risk of lung cancer and non-Hodgkin lymphoma. These findings, consistent with recent reports from post-marketing trials of similar JAK inhibitors, could have important implications for future safety assessment of Deucravacitinib and other TYK2 inhibitors in development.
IMPACT OF WEEKNIGHT AND WEEKEND CURFEWS USING MOBILITY DATA: A CASE STUDY OF BENGALURU URBAN
Authors: Adiga Aniruddha , Athreya Siva , Marathe Madhav , Midthala Jagadish , Rathod Nihesh , Sundaresan Rajesh , Venkataramanan Srinivasan , Yasodharan Sarath
Published: January 2022

Karnataka imposed weeknight and weekend curfews to mitigate the spread of the Omicron variant of SARS-CoV-2. We attempt to assess the impact of curfew using community mobility reports published by Google. Then, we quantify the impact of such restrictions via a simulation study. The pattern of weeknight and weekend curfew, followed by relaxations during the weekdays, seems, at best, to slow and delay the Omicron spread. The simulation outcomes suggest that Omicron eventually spreads and affects nearly as much of the population as it would have without the restrictions. Further, if Karnataka cases trajectory follows the South African Omicron wave trend and the hospitalisation is similar to that observed in well-vaccinated countries (2% of the confirmed cases), then the healthcare requirement is likely within the capacity of Bengaluru Urban when the caseload peaks, with or without the mobility restrictions. On the other hand, if Karnataka cases trajectory follows both the South African Omicron wave trend and the hospitalisation requirement observed there (6.9%), then the healthcare capacity may be exceeded at peak, with or without the mobility restrictions.
Systematically omitting indoor air quality: sub-standard guidance for shelters, group homes and long-term care during the COVID-19 pandemic
Authors: Katz Amy S. , Li Tianyuan , James LLana , Siegel Jeff , O’Campo Patricia
Published: January 2022

Scientific evidence suggests that COVID-19 is transmitted through the air, and can be mitigated using indoor air quality measures such as ventilation and filtration. We set out to explore how Public Health Ontario (PHO) responded to this evidence. PHO is mandated by legislation to share “scientific and technical advice and support” and “contribute to efforts to reduce health inequities” in Ontario, Canada, a jurisdiction of more than 14 million people (Ontario Agency for Health Protection and Promotion Act, 2007). We were particularly interested in how PHO addressed indoor air quality measures in the context of guidance developed for communal facilities such as long-term care homes and congregate settings (e.g. shelters, group homes, detention centres). We reviewed PHO’s public, written COVID-19 guidance specifically designed for long-term care and congregate settings, and published or revised between January, 2021 and October, 2021. We also compared PHO’s COVID-19 checklists for long-term care and congregate settings to PHO’s COVID-19 checklists for schools, camps and doctor’s offices. We found no references to indoor air quality measures in any guidance documents specifically designed for long-term care and congregate settings, including COVID-19 checklists. We did, however, find references to indoor air quality measures in COVID-19 checklists for schools, summer camps and doctor’s offices. We conclude that PHO has provided sub-standard COVID-19 guidance to long-term care and congregate settings, putting workers and residents at greater risk of illness and death, and exacerbating health inequities in Ontario.
Deep Sequence Learning for Assessing Hypertension in Pregnancy from Doppler Signals
Authors: Katebi Nasim , Clifford Gari D.
Published: January 2022

Measuring blood pressure during pregnancy is an essential component of antenatal care, and is critical for detecting adverse conditions such as pre-eclampsia. The standard approach for measuring blood pressure is via manual auscultation by a trained expert or via an oscillometric self-inflating cuff. While both methods can provide reasonably accurate blood pressure measurements when used correctly, non-expert use can lead to significant error. Moreover, such techniques are uncomfortable and can cause bruising, pain and consequential resistance to use / low compliance. In this work, we propose a low-cost onedimensional Doppler-based method for the detection of hypertension in pregnancy.

Using a sample of 653 pregnant women of Mayan descent in highland Guatemala, we recorded up to 10 minutes of 1D Doppler data of the fetus, and blood pressure from both arms using an Omron M7 oscillometric cuff. A hierarchical LSTM network with attention mechanism was trained to classify hypertension in pregnancy, producing an area under the receiveroperator curve of 0.94. A projection of the data into lower dimensions indicates hypertensive cases are located at the periphery of the distribution of the output of the distribution.

This work presents the first demonstration that blood pressure can be measured using Doppler (without occlusion) and may lead to a novel class of blood pressure monitors which allow rapid blood pressure estimation from multiple body locations. Moreover, the association of the predictor with the fetal blood flow indicates that hypertension in the mother has a significant effect on the fetal blood flow.
Estimation of the Lifetime Quality-Adjusted Life Years (QALYs) Lost Due to Syphilis acquired in the United States in 2018
Authors: Lee Kyueun , You Shiying , Li Yunfei , Chesson Harrell , Gift Thomas L. , Berruti Andrés A. , Hsu Katherine , Yaesoubi Reza , Salomon Joshua A. , Rönn Minttu
Published: January 2022

Background

The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018.

Methods

We developed a Markov model which simulates the natural history and long-term sequelae of syphilis. The model was parameterized by sex (men and women), sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to account for health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. We performed probabilistic sensitivity analysis to account for uncertainty in the model’s estimates.

Findings

We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The QALY loss per infection was lower among MSM (0.06) than among MSW (0.15) and women (0.10). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349 (5,071-31,360 95%UI). MSM account for 6,373 (47.7%) of the overall burden, compared to MSW (32.1%) and women (20.2%). For each case of congenital syphilis, we estimated 1.79 (1.43-2.16 95%UI) QALYs lost for the child and 0.06 (0.01-0.14 95%UI) QALYs lost for the mother. These per-case estimates correspond to 2,332 (1,871-2,825 95%UI) and 79 (17-177 95%UI) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018.

Conclusion

Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.
Connectivity dynamics and cognitive variability during aging
Authors: Jauny G. , Eustache F. , Hinault T.
Published: January 2022

Aging is associated by cognitive changes, with strong variations across individuals. One way to characterize this individual variability is to use techniques such as magnetoencephalography (MEG) to measure the dynamics of neural synchronization between brain regions, and the variability of this connectivity over time. Indeed, few studies have focused on fluctuations in the dynamics of brain networks over time and their evolution with age. We therefore characterize aging effects on MEG phase synchrony in healthy young and older adults from the Cam-CAN database. Age-related changes were observed, with an increase in the variability of brain synchronization, as well as a reversal of the direction of information transfer in the default mode network (DMN), in the delta frequency band. These changes in functional connectivity were associated with cognitive decline. Results suggest that advancing age is accompanied by a functional disorganization of dynamic networks, with a loss of communication stability and a decrease in the information transmitted. This could be partly due to the loss of integrity of the network structure.
Position- and scale-invariant object-centered spatial selectivity in monkey frontoparietal cortex dynamically adapts to task demand
Authors: Taghizadeh Bahareh , Fortmann Ole , Gail Alexander
Published: January 2022

Humans utilize egocentric and allocentric spatial information to guide goal-directed movements. Egocentric encoding is a well-known property of brain areas along the dorsal pathway. We ask if dorsal stream reach planning areas like parietal reach region (PRR) and dorsal premotor cortex (PMd) also encode object-centered (allocentric) information. During two consecutive instructed delay periods, rhesus monkeys first memorized an object-relative target position and then planned a reach to this position after the object re-occurred at variable positions with potentially different size. In both areas, we find predominant object-centered encoding during visual memory, which is invariant to object position and object size, and predominant egocentric encoding during reach planning. Such dynamic transition from allo- to egocentric encoding within individual dorsal stream areas contrasts the idea of task-independent functional segregation between processing pathways. Instead, demand-specific local computations might facilitate spatial cognition in dynamic environments to facilitate motor planning towards objects changing their location.

Significance statement

Human and non-human primates interact with their environment by manipulating objects. This requires planning and executing reaches to transport the hand to object-relative positions close to or on the object. Previous studies showed that frontal and parietal lobe areas encode reach goals in coordinate systems anchored to different parts of the subjects’ body, such as hand position or gaze direction, and modulated by pose. We show that neurons in the same areas can encode object-centered allocentric spatial information, independent of object location and object size, or egocentric information, depending on dynamically changing task demands. Such dynamic adaptation seems inconsistent with a functional segregation for ego- and allocentric encoding between processing streams.
Diabetes mellitus, hypertension, and HbA1c, as risk factors for arterial stiffness
Authors: Regla Rafaela Pelisson , Okawa Rogério Toshiro Passos , de Oliveira Edilson Almeida , do Nascimento Rafael Campos , de Araújo Milene Cripa Pizatto , Duarte Giovanna Chiqueto , Gargaro Lorena Lima , da Cruz Marina Franciscon Gomes , Perez Alex Cardoso , Hayakawa Guilherme Norio , da Silva Guedes de Moura Barbara Letícia , Teixeira Jorge Juarez Vieira
Published: January 2022

Studies in a healthy and diabetic population have shown that there is a correlation between the disease and arterial stiffness, and consequently an increase in Pulse Wave Velocity (PWV). We investigate predictors laboratory and clinical associated with arterial stiffness, validated by the increase in PWV. Our findings showed that the predictor for diabetes mellitus, hypertension, glycated hemoglobin ≥5.7, confirmed the significant association for increased arterial stiffness, validated by the increase in PWV.
A non-systematic signal-correction error in a commercial multiple-breath washout device significantly impacts outcomes in children and adults
Authors: Oestreich Marc-Alexander , Wyler Florian , Etter Blaise , Ramsey Kathryn A. , Latzin Philipp
Published: January 2022

Background

Multiple-breath nitrogen washout is an established and sensitive technique to assess functional residual capacity and ventilation inhomogeneity in the lung. Indirect calculation of nitrogen concentration requires precise calibration and accurate measurement of gas concentrations.

Aim

We investigated the accuracy of the carbon dioxide gas concentration used for the indirect calculation of nitrogen concentration in a commercial multiple-breath washout (MBW) device (EasyOne Pro LAB, ndd Medizintechnik AG, Zurich, Switzerland) and its impact on outcomes.

Methods

A high-precision calibration gas mixture was used to evaluate sensor output and calculated carbon dioxide concentration. We assessed the impact of a corrected CO2 signal on MBW outcomes in a dataset of healthy children and adults and children with lung disease.

Results

The EasyOne device uses a respiratory quotient-based adjustment to correct the measured carbon dioxide signal for potential long-term changes in sensor output. In the majority of measurements (89%), this resulted in an overestimation of expired nitrogen concentrations (range -0.7 to 1.7%), and consequently MBW outcomes. Correction of the CO2 signal reduced the mean (range) cumulative expired volume by 27.1% (−58.1%; 1.0%), functional residual capacity by 11.1% (−21.6%; 1.2%), and lung clearance index by 18.3% (−44.0%; -0.3%). Additionally, within-visit variability was substantially reduced with the corrected signals.

Conclusion

Inadequate signal-correction of the measured CO2 concentration in the EasyOne Pro LAB device leads to a non-systematic error in expired nitrogen concentrations and overestimation of test outcomes. Two-point calibration of the CO2 sensor may maintain accurate measurement of gas concentrations and overcome this error.
Clinical, Environmental, and Genetic Risk Factors for Substance Use Disorders: Characterizing Combined Effects across Multiple Cohorts
Authors: Barr Peter B. , Driver Morgan N. , Kuo Sally I-Chun , Stephenson Mallory , Aliev Fazil , Karlsson Linnér Richard , Marks Jesse , Anokhin Andrey P. , Bucholz Kathleen , Chan Grace , Edenberg Howard J. , Edwards Alexis C. , Francis Meredith W. , Hancock Dana B. , Harden K. Paige , Kamarajan Chella , Kaprio Jaakko , Kinreich Sivan , Kramer John , Kuperman Samuel , Latvala Antti , Meyers Jacquelyn L. , Palmer Abraham A. , Plawecki Martin H. , Porjesz Bernice , Rose Richard J. , Schuckit Marc A. , Salvatore Jessica E. , Dick Danielle M.
Published: January 2022

Substance use disorders (SUDs) incur serious social and personal costs. Risk for SUDs is complex, ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2,475) ancestries. SUD outcomes included: 1) alcohol dependence, 2) nicotine dependence; 3) drug dependence, and 4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 1.37 – 1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11 – 1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09 – 1.18). The full model explained 6% - 13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86 - 8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.
Mortality and predictors of Chronic Kidney Diseases (CKD) in selected dialysis centers in Addis Ababa, Ethiopia
Authors: Desta Beza Zewdu , Derseh Behailu Tariku , Dadi Abel Fekadu
Published: January 2022

Background

Chronic Kidney Disease (CKD) affects 10-15% of the population worldwide. The number of dialysis patients is steadily rising in Ethiopia. Chronic hemodialysis patients experience high rates of mortality; however, data is lacking in Ethiopia. We explored the mortality and its driving factors in selected dialysis center in Addis Ababa

Method

we retrospectively followed a group of End-Stage Renal Disease patients on hemodialysis from 2016 to2020 in St. Paul Millennium Medical College (SPMMC), Zewditu Memorial Hospital (ZMH), and Menellik II Hospital. We fitted Kaplan Meier analysis to estimate the one and five year’s survival probability of these patients and Cox Proportional regression analysis to model the predictors of mortality at p value ≤0.05.

Result

We analyzed a data of (139) patients under follow up. The mean age (± SD) of the patients was 36.8 (±11.95) years. Twenty-four (17%) of the patients died at the end of follow-up. The median survival time was 46.2 months (95% CI: 41.8, 50.5). The one and five-year’s survival probability of these patients was 64.8% and 18.7%, respectively. Our analysis showed that patients with hypertension (AHR = 4.33; 95% CI: 1.02, 34.56), cardiac complication (AHR = 4.69; 95% CI: 1.32, 16.8), and infection during dialysis (AHR = 3.89; 95% CI: 1.96, 13.8) were more likely to die.

Conclusion

The survival status of hemodialysis patients in three was low. Preventing and treating comorbidities and complication during dialysis would reduce mortality of CKD patients.