bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Hepatitis B Screening Into Routine Antenatal Care to Prevent Mother-to-Child Transmission in Rural Western Uganda
Authors: Thahir Sahal , Muhindo Enid , Turigye Brian , Kabagambe Kenneth , Thompson Peyton , Mulogo Edgar M , Boyce Ross M
Published: August 2023

In rural Uganda where birth dose vaccination for hepatitis B is not routine, we implemented a pilot program for preventing mother-to-child transmission that effectively identified women with high-risk hepatitis B virus (HBV) infection and started antiviral treatment during pregnancy. Further work is required to enhance antiviral adherence through delivery to ensure effective prevention of vertical HBV transmission.
Veridicalism and Scepticism
Authors: Avnur Yuval
Published: August 2023

According to veridicalism, your beliefs about the existence of ordinary objects are typically true, and can constitute knowledge, even if you are in some global sceptical scenario. Even if you are a victim of Descartes’ demon, you can still know that there are tables, for example. Accordingly, even if you don’t know whether you are in some such scenario, you still know that there are tables. This refutes the standard sceptical argument. But does it solve the sceptical problem posed by that argument? I argue that it does not, because we do not know substantively more about the external world according to veridicalism than we do according to the sceptical argument. Rather, veridicalism merely reformulates what little knowledge we have. I then draw some general conclusions about the nature of the sceptical problem, the formulation of the standard argument, and the significance of this for some other, non-veridicalist strategies.
Grandparenting during pandemic times: pros and cons for mental health
Authors: Vigezzi Giacomo Pietro , Bertuccio Paola , Amerio Andrea , Bottini Gabriella , Gandola Martina , Cavalieri d’Oro Luca , Iacoviello Licia , Stuckler David , Signorelli Carlo , Zucchi Alberto , Gallus Silvano , Odone Anna ,   Lost in Lombardia Project Investigators, Amerio A , Amore M , Bertuccio P , Bonaccio M , Bosetti C , Cavalieri d’Oro L , Ciampichini R , De Sena R , Gallus S , Gianfagna F , Ghislandi S , Ghulam A , Iacoviello L , Jarach C M , Lugo A , Mosconi G , Odone A , Rognoni M , Serafini G , Scala M , Signorelli C , Stival C , Stuckler D , Vigezzi G P , Wang Y , Zucchi A
Published: August 2023

Background

The COVID-19 pandemic and associated lockdown measures posed an unprecedented challenge to the crucial role of grandparenting in family-oriented cultures, such as Italy. Reduced contact with grandchildren during this period potentially threatened grandparents’ mental health and well-being.

Methods

We analysed data from the LOckdown and lifeSTyles in Lombardia cross-sectional study conducted in November 2020. The study included a representative sample of 4400 older adults from Lombardy, Italy, of which 1289 provided childcare to their grandchildren.

Results

A decrease in self-reported grandparenting was associated with an increased likelihood of experiencing depressive symptoms among grandparents (OR 1.50, 95% CI 1.01–2.24). Conversely, an increase in grandparenting was linked to poorer sleep quality (OR 11.67, 95% CI 5.88–23.17) and reduced sleep quantity (OR 2.53, 95% CI 1.45–4.41).

Conclusions

Despite the barriers posed by the pandemic, grandparenting played a beneficial role in maintaining the mental health and well-being of older adults. However, it is crucial to recognise specific vulnerabilities, such as gender, feelings of hopelessness and overcrowding, which can have detrimental effects during and beyond emergency situations. Careful attention to these factors is essential for developing targeted support systems and interventions aimed at safeguarding the mental health of older adults and enhancing their resilience in crises.
A millimetre-wave superconducting hyper-spectral device
Authors: Chowdhury U , Calvo M , Goupy J , Levy-Bertrand F , Monfardini A
Published: August 2023

Millimetre-wave observations represent an important tool for cosmology studies. The line intensity mapping technique has been proposed to map in three dimensions the specific intensity due to line (e.g. [C ii] and CO) emission, e.g. from the primordial galaxies, as a function of redshift. Hyper-spectral integrated devices have the potential to replace the current Fourier transform, or the planned Fabry–Perot-based instruments operating at millimetre and sub-millimetre wavelengths. The aim is to perform hyper-spectral mapping, with a spectral resolution R = λ/Δλ = 100–1000, over large, i.e. thousands of beams, instantaneous patches of the sky. The innovative integrated device that we have developed allows avoiding moving parts, complicated and/or dispersive optics, or tunable filters to be operated at cryogenic temperatures. The prototype hyper-spectral focal plane is sensitive in the 75- to 90-GHz range and contains 19 horns for 16 spectral-imaging channels, each selecting a frequency band of about 0.1 GHz. For each channel a conical horn antenna, coupled to a planar superconducting resonant absorber made of thin aluminium, collects the radiation. A capacitively coupled titanium–aluminium bi-layer Lumped Element Kinetic Inductance Detector is then in charge of dissipating and sensing the supercurrent established in the resonant absorber. The prototype is fabricated with only two photolithography steps over a commercial mono-crystalline sapphire substrate. It exhibits a spectral resolution R = λ/Δλ ≈ 800. The optical noise equivalent power of the best channels is in the observational relevant $4\cdot 10^{-17} W/\sqrt{Hz}$ range. The average sensitivity of all the channels is around $1\cdot 10^{-16} W/\sqrt{Hz}$. The device, as expected from three-dimensional simulations, is polarization-sensitive, paving the way to spectro-polarimetry measurements over very large instantaneous field of views.
Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study
Authors: Chan Eugene Yu-hin , Yap Desmond Yat-hin , Wong Wilfred Hing-sang , Wong Sze-wa , Lin Kyle Ying-kit , Hui Felix Yan-wai , Li Jennifer Yee-ming , Lam Sophia Suet-ying , Wong Jennie Kit-yee , Lai Fiona Fung-yee , Ho Tsz-wai , Tong Pak-chiu , Lai Wai-ming , Chan Tak Mao , Ma Alison Lap-tak
Published: August 2023

Objectives

There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse.

Methods

We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001–2021 to investigate the incidence and outcomes related to renal relapse.

Results

Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [n = 36 (38%)] or MMF [n = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [n = 53 (54%)] or AZA [n = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s.d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3–5) and end-stage kidney disease (17.9% vs 1.8%, P < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P = 0.02), osteopenia (38.5% vs 17.9%, P = 0.04) and hypertension (30.8% vs 7.1%, P < 0.01).

Conclusion

Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse.
Openness to Experience is associated with neural and performance measures of memory in older adults
Authors: Stolz Christopher , Bulla Ariane , Soch Joram , Schott Björn H , Richter Anni
Published: August 2023

Age-related decline in episodic memory performance is a well-replicated finding across numerous studies. Recent studies focusing on aging and individual differences found that the Big Five personality trait Openness to Experience (hereafter: Openness) is associated with better episodic memory performance in older adults, but the associated neural mechanisms are largely unclear. Here, we investigated the relationship between Openness and memory network function in a sample of 352 participants (143 older adults, 50–80 years; 209 young adults, 18–35 years). Participants underwent functional magnetic resonance imaging (fMRI) during a visual memory encoding task. Functional memory brain–network integrity was assessed using the similarity of activations during memory encoding (SAME) scores, which reflect the similarity of a participant’s memory network activity compared to prototypical fMRI activity patterns of young adults. Openness was assessed using the NEO Five-Factor Inventory. Older vs young adults showed lower memory performance and higher deviation of fMRI activity patterns (i.e. lower SAME scores). Specifically in older adults, high Openness was associated with better memory performance, and mediation analysis showed that this relationship was partially mediated by higher SAME scores. Our results suggest that trait Openness may constitute a protective factor in cognitive aging by better preservation of the brain’s memory network.
Latent Cumulative Disadvantage: US Immigrants’ Reversed Economic Assimilation in Later Life
Authors: Ye Leafia Z
Published: August 2023

One of the most salient findings in research on immigration has been that immigrants experience substantial economic mobility as they accumulate more years in the host-society labor force and eventually approach earnings parity with their native-born counterparts. However, we do not know whether this progress is sustained in retirement. In this paper, I develop a framework of Latent Cumulative (Dis)advantage and hypothesize that even as immigrants are approaching parity with the native-born in terms of current earnings, they accumulate disadvantages in lifetime earnings, job benefits, and retirement planning that eventually lead them to have growing disadvantages in income in later life. Drawing on decades of longitudinal data from the Health and Retirement Study, I find that while foreign- and native-born men in the United States both experience a decline in income after age 50, the decline is much more substantial among foreign-born men. As a result, immigrant men’s economic assimilation is reversed in later life. I find evidence that this phenomenon is driven mainly by immigrants’ lower lifetime earnings and cumulative exposure to worse job benefits. Given that the foreign-born elderly population in the United States is projected to quadruple by 2050, findings from this paper have important implications for long-term policy planning.
Production and Limbal Lineage Commitment of Aniridia Patient-Derived Induced Pluripotent Stem Cells
Authors: Ilmarinen Tanja , Vattulainen Meri , Kandhavelu Jeyalakshmi , Bremond-Gignac Dominique , Aberdam Daniel , Skottman Heli
Published: August 2023

Congenital aniridia is caused by heterozygous mutations on the PAX6 gene leading to reduced amount of PAX6 protein (haploinsufficiency), abnormal eye development, and aniridia-associated keratopathy (AAK). This progressive corneal opacification resembles late-onset limbal stem cell (LSC) deficiency, leading to disrupted corneal epithelial renewal. The factors leading to AAK are not known and defects in native LSC differentiation and/or features leading to ocular surface dysfunction like inflammation and loss of innervation could contribute to development of AAK. Here, we produced induced pluripotent stem cells (hiPSC) from 3 AAK patients and examined whether PAX6 haploinsufficiency affects LSC lineage commitment. During LSC differentiation, characterization of the AAK lines showed lowered PAX6 expression as compared to wild type (WT) controls and expression peak of PAX6 during early phase of differentiation was detected only in the WT hiPSC lines. Whether it reflects developmental regulation remains to be studied further. Nevertheless, the AAK-hiPSCs successfully differentiated toward LSC lineage, in line with the presence of LSCs in young patients before cell loss later in life. In addition, patient-specific LSCs showed similar wound healing capacity as WT cells. However, extensive batch-related variation in the LSC marker expression and wound healing efficacy was detected without clear correlation to AAK. As development and maintenance of corneal epithelium involves an interplay between LSCs and their environment, the AAK-hiPSCs generated here can be further used to study the crosstalk between LSCs and limbal niche including, eg, corneal immune cells, stroma cells, and neurons.
Family-based pediatric weight management interventions in US primary care settings targeting children ages 6–12 years old: A systematic review guided by the RE-AIM framework
Authors: Yudkin Joshua S , Koym Kelsey , Hamad Yasmin , Malthaner Lauren Q , Burgess Rebecca Meredith , Ortiz Leslie N , Dhurjati Nalini , Mitha Sharmin , Calvi Gabriela , Hill Kristina , Brownell Mckenna , Wei Elena , Swartz Kyle , Atem Folefac D , Galeener Carol A , Messiah Sarah E , Barlow Sarah E , Allicock Marlyn A
Published: August 2023

Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6–12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions.
An integrated approach for early in vitro seizure prediction utilizing hiPSC neurons and human ion channel assays
Authors: Rockley Kimberly , Roberts Ruth , Jennings Hannah , Jones Karen , Davis Myrtle , Levesque Paul , Morton Michael
Published: August 2023

Seizure liability remains a significant cause of attrition throughout drug development. Advances in stem cell biology coupled with an increased understanding of the role of ion channels in seizure offer an opportunity for a new paradigm in screening. We assessed the activity of 15 pro-seizurogenic compounds (7 CNS active therapies, 4 GABA receptor antagonists, and 4 other reported seizurogenic compounds) using automated electrophysiology against a panel of 14 ion channels (Nav1.1, Nav1.2, Nav1.6, Kv7.2/7.3, Kv7.3/7.5, Kv1.1, Kv4.2, KCa4.1, Kv2.1, Kv3.1, KCa1.1, GABA α1β2γ2, nicotinic α4β2, NMDA 1/2A). These were selected based on linkage to seizure in genetic/pharmacological studies. Fourteen compounds demonstrated at least one “hit” against the seizure panel and 11 compounds inhibited 2 or more ion channels. Next, we assessed the impact of the 15 compounds on electrical signaling using human-induced pluripotent stem cell neurons in microelectrode array (MEA). The CNS active therapies (amoxapine, bupropion, chlorpromazine, clozapine, diphenhydramine, paroxetine, quetiapine) all caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency and duration. The GABA antagonist picrotoxin increased all parameters, but the antibiotics amoxicillin and enoxacin only showed minimal changes. Acetaminophen, included as a negative control, caused no changes in any of the parameters assessed. Overall, pro-seizurogenic compounds showed a distinct fingerprint in the ion channel/MEA panel. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources.
Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis
Authors: Lastuvkova Hana , Nova Zuzana , Hroch Milos , Alaei Faradonbeh Fatemeh , Schreiberova Jolana , Mokry Jaroslav , Faistova Hana , Stefela Alzbeta , Dusek Jan , Kucera Otto , Hyspler Radomír , Dohnalkova Ester , Bayer Rachel L , Hirsova Petra , Pavek Petr , Micuda Stanislav
Published: August 2023

Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, we determined the effect of carvedilol (10 mg/kg/day p.o.) on bile formation and bile acid (BA) turnover in male C57BL/6 mice consuming either a chow diet or a western-type NASH-inducing diet. BAs were profiled by liquid chromatography-mass spectrometry and BA-related enzymes, transporters, and regulators were evaluated by western blot analysis and qRT-PCR. In chow diet-fed mice, carvedilol increased plasma concentrations of BAs resulting from reduced BA uptake to hepatocytes via Ntcp transporter downregulation. Inhibition of the β-adrenoreceptor-cAMP-Epac1-Ntcp pathway by carvedilol may be the post-transcriptional mechanism underlying this effect. In contrast, carvedilol did not worsen the deterioration of BA homeostasis accompanying NASH; however, it shifted the spectra of BAs toward more hydrophilic and less toxic α-muricholic and hyocholic acids. This positive effect of carvedilol was associated with a significant attenuation of liver steatosis, inflammation, and fibrosis in NASH mice. In conclusion, our results indicate that carvedilol may increase BAs in plasma by modifying their liver transport. In addition, carvedilol provided significant hepatoprotection in a NASH murine model without worsening BA accumulation. These data suggest beneficial effects of carvedilol in patients at high risk for developing NASH.
CD30 in Cutaneous Pathology
Authors: Fernandez-Flores Angel , Cassarino David
Published: August 2023

The discovery of CD30 as a diagnostic marker was essential in the identification of not only some lymphomas but also many other solid tumors and benign reactive conditions. Many CD30+ cutaneous disorders and tumors have been categorized since the identification of the marker. With the design of targeted therapies against CD30+ tumoral cells, the interest in CD30 determination was not only diagnostic but also mainly therapeutic. In this article, we explore the historical aspects of the discovery of CD30 and examine the main CD30-related cutaneous pathology, susceptible of anti-CD30 modern treatments.
Sarcoidal Granuloma Annulare–Like Dermatitis and Vasculitis With Granulomatous Features: An Atypical Case of Giant Cell Arteritis
Authors: Kye Yae , Hales Molly , See Sharlene Helene C. , Nguyen Cuong V.
Published: August 2023

Giant cell arteritis (GCA) is a diagnosis that clinicians should not miss because of the accompanying risk of irreversible vision loss. GCA can present without the classic symptoms of headache and temporal artery tenderness, which may lead to a delay in diagnosis. Cutaneous findings, although rare, have been associated with GCA. Accordingly, it is imperative to be aware of the broad clinical and histological presentations of GCA, including the cutaneous findings, because they may prove to be harbingers of impending disease. We present a unique case of GCA where 2 distinct cutaneous morphologies, sarcoidal granuloma annulare–like dermatitis and leukocytoclastic vasculitis with granulomatous features, presented simultaneously before the classic symptoms of headache and unilateral vision loss.
Comparison of Loading-Displacement Relationships and Energy-Storing Properties of the Jaipur Foot Against Low-, Mid-, and High-Activity Prosthetic Feet Using Static Proof Testing
Authors: Telford Jeremy C. , Arnold Graham P. , Drew Tim
Published: August 2023

Introduction

The Jaipur foot is a low-cost prosthetic foot developed in Jaipur, India. Despite its worldwide use, few data are available on its mechanical properties. In general, there is a lack of objective data on the mechanical performance of prosthetic feet, hindering the objectivity of the prosthetic foot prescription process. The aim of this project was to compare the properties of the Jaipur foot with three prosthetic feet of differing activity levels (a SACH foot and two ESPFs) used commonly in the UK National Health Service (NHS), specifically evaluating loading-displacement relationships and energy-storing properties.

Materials and Methods

Static proof testing was performed on the four prosthetic feet (BMVSS Jaipur foot, 1D10 Dynamic, 1C30 Trias, and 1C60 Triton) using ISO:10328 methods. Loading-displacement graphs for the forefoot and heel were produced, from which instantaneous stiffness at forces typical of walking and running was produced and energy-storing properties were calculated.

Results

The Jaipur foot demonstrated the highest heel stiffness at both walking and running forces, the highest forefoot stiffness at walking forces, and the lowest energy return of the four feet overall. The ESPFs demonstrated the lowest forefoot stiffness, along with the highest energy returns.

Conclusions

Although low cost and cultural requirements should be taken into account, these data have demonstrated the inferior energy-storing properties of the Jaipur foot compared with Western prosthetic feet, using ISO methods to allow future cross-study comparison.

Clinical Relevance

The mechanical and energy-storing data from this study can be compared with other research using ISO methods to make the prosthetic prescription process more objective, allowing the most appropriate choices to be made for patients.
eGADA: enhanced Genomic Alteration Detection Algorithm, a fast genomic segmentation algorithm based on Sparse Bayesian Learning
Authors: Huang Yu S.
Published: August 2023

eGADA is an enhanced version of GADA, which is a fast segmentation algorithm utilizing the Sparse Bayesian Learning (or Relevance Vector Machine) technique from Tipping 2001. It can be applied to array intensity data, NGS sequencing coverage data, or any sequential data that displays characteristics of stepwise functions. Improvements by eGADA over GADA include:a) a customized Red-Black tree to expedite the final backward elimination step of GADA;b) code in C++, which is safer and better structured than C;c) use Boost libraries extensively to provide user-friendly help and commandline argument processing;d) user-friendly input and output formats;e) export a dynamic library eGADA.so (packaged via Boost.Python) that offers API to Python;f) other bug fixes/optimization. The code is published athttps://github.com/polyactis/eGADA.
“Emotional stress is more detrimental than the virus itself”: Towards an understanding of HIV testing and pre-exposure prophylaxis (PrEP) use among internal migrant men in South Africa
Authors: Nardell Maria F. , Govathson Caroline , Garnier Salomé , Watts Ashley , Babalola Dolapo , Ngcobo Nkosinathi , Long Lawrence , Lurie Mark N. , Miot Jacqui , Pascoe Sophie , Katz Ingrid T.
Published: August 2023

Introduction

South Africa has one of the highest rates of internal migration on the continent, largely comprised of men seeking labor in urban centers. South African men who move within the country (internal migrants) are at higher risk than non-migrant men of acquiring HIV yet are less likely to test or use pre-exposure prophylaxis (PrEP). However, little is known about the mechanisms that link internal migration and challenges engaging in HIV services.

Methods

We recruited 30 internal migrant men (born outside Gauteng Province) for in-depth qualitative interviews at sites in Johannesburg (Gauteng) where migrants may gather (i.e., factories, homeless shelters). Interviewers used open-ended questions, based in the Theory of Triadic Influence, to explore experiences and challenges with HIV testing and/or PrEP. A mixed deductive inductive content analytic approach was used to review data and explain why participants may or may not use these services.

Results

Migrant men come to Johannesburg to find work, but their struggle to survive without reliable income causes daily stress. Stress and time constraints limit their availability to seek health services, and many men lack knowledge about the opportunity for PrEP should they test negative. In addition, migrants must also adjust to life in Johannesburg, where they may be unfamiliar with where to access HIV services and lack social support to help them do so. Migrants may also continue to travel intermittently for work or social purposes, which can make it hard to take a daily pill like PrEP. Yet Johannesburg also presents opportunities for HIV services for migrant men, especially those who perceive greater availability and anonymity of HIV information and services in the city as compared to their rural homes of origin.

Conclusions

Bringing HIV services to migrant men at community sites may ease the burden of accessing these services. Including PrEP counseling and services alongside HIV testing may further encourage men to test, particularly if integrated into counseling for livelihood and coping strategies, as well as support for navigating health services in Johannesburg.
AORTA Gene: Polygenic prediction improves detection of thoracic aortic aneurysm
Authors: Pirruccello James P. , Khurshid Shaan , Lin Honghuang , Weng Lu-Chen , Zamirpour Siavash , Kany Shinwan , Raghavan Avanthi , Koyama Satoshi , Vasan Ramachandran S. , Benjamin Emelia J. , Lindsay Mark E. , Ellinor Patrick T.
Published: August 2023

Background

Thoracic aortic disease is an important cause of morbidity and mortality in the US, and aortic diameter is a heritable contributor to risk. Could a polygenic prediction of ascending aortic diameter improve detection of aortic aneurysm?

Methods

Deep learning was used to measure ascending thoracic aortic diameter in 49,939 UK Biobank participants. A genome-wide association study (GWAS) was conducted in 39,524 participants and leveraged to build a 1.1 million-variant polygenic score withPRScs-auto. Aortic diameter prediction models were built with the polygenic score (“AORTA Gene”) and without it. The models were tested in a held-out set of 4,962 UK Biobank participants and externally validated in 5,469 participants from Mass General Brigham Biobank (MGB), 1,298 from the Framingham Heart Study (FHS), and 610 participants fromAll of Us.

Results

In each test set, the AORTA Gene model explained more of the variance in thoracic aortic diameter compared to clinical factors alone: 39.9% (95% CI 37.8-42.0%) vs 29.2% (95% CI 27.1-31.4%) in UK Biobank, 36.5% (95% CI 34.4-38.5%) vs 32.5% (95% CI 30.4-34.5%) in MGB, 41.8% (95% CI 37.7-45.9%) vs 33.0% (95% CI 28.9-37.2%) in FHS, and 34.9% (95% CI 28.8-41.0%) vs 28.9% (95% CI 22.9-35.0%) inAll of Us. AORTA Gene had a greater AUROC for identifying diameter ≥4cm in each test set: 0.834 vs 0.765 (P=7.3E-10) in UK Biobank, 0.808 vs 0.767 in MGB (P=4.5E-12), 0.856 vs 0.818 in FHS (P=8.5E-05), and 0.827 vs 0.791 (P=7.8E-03) inAll of Us.

Conclusions

Genetic information improved estimation of thoracic aortic diameter when added to clinical risk factors. Larger and more diverse cohorts will be needed to develop more powerful and equitable scores.
Utilizing the Amide Proton Transfer Technique to Characterize Diffuse Gliomas Based on the WHO 2021 Classification of CNS Tumors
Authors: Filimonova Elena , Pashkov Anton , Borisov Norayr , Kalinovsky Anton , Rzaev Jamil
Published: August 2023

Purpose

Diffuse gliomas present a significant challenge for healthcare systems globally. While brain MRI plays a vital role in diagnosis, prognosis, and treatment monitoring, accurately characterizing gliomas using conventional MRI techniques alone is challenging. In this study, we explored the potential of utilizing the amide proton transfer (APT) technique alone or in combination with other quantitative MRI sequences to predict tumor grade and type based on the WHO 2021 Classification of CNS Tumors.

Methods

Forty-two adult patients with histopathologically confirmed brain gliomas were included in the study. They underwent 3T MRI imaging, which involved APT, arterial spin labeling (ASL), and diffusion-weighted imaging sequences. Multinomial and binary logistic regression models were employed to classify patients into clinically relevant groups based on MRI findings and demographic variables.

Results

We found that the best model for tumor grade classification included patient age along with APT values. The highest sensitivity (88%) was observed for Grade 4 tumors, while Grade 3 tumors showed the highest specificity (79%). For tumor type classification, our model incorporated four predictors: APT values, necrosis, and the presence of hemorrhage. The glioblastoma group had the highest sensitivity and specificity (87%), whereas balanced accuracy was the lowest for astrocytomas, indicating that the model performs better at detecting patients with glioblastoma rather than astrocytomas.

Conclusion

The APT technique shows great potential for noninvasive evaluation of diffuse gliomas. The changes in the classification of gliomas as per the WHO 2021 version of the CNS Tumor Classification did not affect its usefulness in predicting tumor grade or type.
RareCRHR2andGRM8variants identified as candidate factors associated with eating disorders in Japanese patients
Authors: Oka Akira , Hadano Shinji , Ueda Mahoko Takahashi , Nakagawa So , Komaki Gen , Ando Tetsuya
Published: August 2023

Eating disorders (EDs) are a type of psychiatric disorder characterized by pathological eating and related behavior and considered to be highly heritable. The purpose of this study was to explore rare variants expected to display biological functions associated with the etiology of EDs. We performed whole exome sequencing (WES) of affected sib-pairs corresponding to disease subtype through their lifetime and their parents. From those results, rare single nucleotide variants (SNVs) concordant with sib-pairs were extracted and estimated to be most deleterious in the examined families. Two non-synonymous SNVs located on corticotropin releasing hormone receptor 2 (CRHR2) and glutamate metabotropic receptor 8 (GRM8) were identified as candidate disease susceptibility factors. The SNV ofCRHR2was included within the cholesterol binding motif of the transmembrane helices region, while the SNV ofGRM8was found to contribute to hydrogen bonds for an α-helix structure. CRHR2 plays important roles in the serotoninergic system of dorsal raphe nuclei, which is involved with feeding and stress-coping behavior. Moreover, GRM8 modulates glutamatergic neurotransmission, and is also considered to have effects on dopaminergic and adrenergic neurotransmission. Further investigation regarding the biological function of these variants may provide an opportunity for elucidate the pathogenesis of EDs.
Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults
Authors: Lee Nelson , Nguyen Lena , Austin Peter C. , Brown Kevin A. , Grewal Ramandip , Buchan Sarah A , Nasreen Sharifa , Gubbay Jonathan , Schwartz Kevin L , Tadrous Mina , Wilson Kumanan , Wilson Sarah E , Kwong Jeffrey C
Published: August 2023

Introduction

We assessed protection conferred by COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods.

Methods

We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged ≥50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2−5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection.

Results

We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose,6-month: 68%, 95%CI 63%−72%;fourth-dose,6-month: 80%, 95%CI 77%−83%), but was lower and waned quickly during BQ/XBB predominance (third-dose,6-month: 59%, 95%CI 48%−67%; 12-month: 49%, 95%CI 41%−56%;fourth-dose,6-month: 62%, 95%CI 56%−68%, 12-months: 51%, 95%CI 41%−56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose,6-month: 60%, 95%CI 36%−75%;fourth-dose,6-month: 63%, 95%CI 42%−76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%−96%). Prior infection alone did not confer lasting protection.

Conclusion

Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.
Predicting graft and patient outcomes following kidney transplantation using interpretable machine learning models
Authors: Salaün Achille , Knight Simon , Wingfield Laura , Zhu Tingting
Published: August 2023

The decision to accept a deceased donor organ offer for transplant, or wait for something potentially better in the future, can be challenging. Clinical decision support tools predicting transplant outcomes are lacking. This project uses interpretable methods to predict both graft failure and patient death using data from previously accepted kidney transplant offers. Using more than twenty years of transplant outcome data, we train and compare several survival analysis models in single risk settings. In addition, we usepost hocinterpretability techniques to clinically validate these models. Neural networks show comparable performance to the Cox proportional hazard model, with concordance of 0.63 and 0.79 for prediction of graft failure and patient death, respectively. Recipient and donor ages, primary renal disease, the number of mismatches at DR locus, and calculated reaction frequency at transplant appear to be important features for transplant outcome prediction. Owing to their good predictive performance and the clinical relevance of theirpost hocinterpretation, neural networks represent a promising core component in the construction of future decision support systems for transplant offering.
Association of cultural participation with morbidity and mortality in the Welsh Population: An observational study
Authors: Jones Daniel Peter , Hurt Lisa , Daniel Rhian
Published: August 2023

Background

Clinical interventions based on cultural participation have consistently demonstrated improved patient outcomes. At the population level, prospective cohort studies show a protective association between cultural participation and all-cause mortality. However, the latter is limited by a narrow choice of methods and outcomes. We sought to address this by using multiple methods to investigate the effects of cultural participation on both morbidity and mortality.

Methods

First, we conducted multivariable linear and logistic regression models using the National Survey of Wales 2015-2019. This featured attendance at cultural events/activities as an exposure and self-reported health (SRH), as well as specific health conditions, as an outcome with sequential adjustment for confounders related to demographics, socio-economic position (SEP), and lifestyle behaviours. To complement this, we conducted a multivariable panel regression model using cultural expenditure data from English and Welsh local authorities and life expectancy data from the Office for National Statistics.

Results

When adjusting for age, sex, SEP, and lifestyle behaviours, we found that overall cultural participation had a small positive association with SRH (4.8% improvement in SRH score, 95% confidence intervals [4.0-5.6%], p<0.0001, n=15374) and lower likelihood of cardiovascular disease, and anxiety/depression. Similar, albeit smaller, positive associations were seen between SRH and individual cultural activities, including library, museum, and heritage site visits. However, we did not identify any association between local authority cultural expenditure and local life expectancy.

Conclusion

We identified new evidence for a positive association between cultural participation and morbidity. However, additional evidence will be required to better establish causal inference.

What is already known on this topic?

Several observational studies show that cultural participation is associated with reduced mortality and clinical trials also support the use of cultural interventions.

What this study adds?

This study provides evidence for beneficial associations between cultural participation, self-reported health, and certain chronic conditions even when taking account of known confounders.

How this study might affect research, practice or policy?

This study further emphasises the importance of arts and culture for health and the need for further research in this area of epidemiology.
Non-detection of emerging and re-emerging pathogens in wastewater surveillance to confirm absence of transmission risk: a case study of polio in New York
Authors: Larsen David A , Hill Dustin , Zhu Yifan , Alazawi Mohammed , Chatila Dana , Dunham Christopher , Faruolo Catherine , Ferro Brandon , Godinez Alejandro , Hanson Brianna , Insaf Tabassum , Lang Dan , Neigel Dana , Neyra Milagros , Pulido Nicole , Wilder Max , Yang Nan , Kmush Brittany , Green Hyatt
Published: August 2023

Infectious disease surveillance systems, including wastewater surveillance, can alert communities to the threat of emerging pathogens. We need methods to infer understanding of transmission dynamics from non-detection. We estimate a sensitivity of detection of poliovirus in wastewater to inform the sensitivity of wastewater surveillance for poliovirus using both a clinical epidemiology and fecal shedding approach. We then apply freedom from disease to estimate the sensitivity of the wastewater surveillance network. Estimated sensitivity to detect a single poliovirus infection was low, <11% at most wastewater treatment plants and <3% in most counties. However, the maximum threshold for the number of infections when polio is not detected in wastewater was much lower. Prospective wastewater surveillance can confirm the absence of a polio threat and be escalated in the case of poliovirus detection. These methods can be applied to any emerging or re-emerging pathogen, and improve understanding from wastewater surveillance.
Usability and Accuracy of the SWIFT-ActiveScreener: Preliminary evaluation for use in clinical research
Authors: Liu Jenny J.W. , Ein Natalie , Gervasio Julia , Easterbrook Bethany , Nouri Maede S. , Nazarov Anthony , Richardson J. Don
Published: August 2023

Systematic reviews (SRs) employ standardized methodological processes for synthesizing empirical evidence to answer specific research questions. These processes include rigorous screening phases to determine eligibility of articles against strict inclusion and exclusion criteria. Despite these processes, SRs are a significant undertaking, and this type of research often necessitates extensive human resource requirements, especially when the scope of the review is large. Given the substantial resources and time commitment required, we investigated a way in which the screening process might be accelerated while maintaining high fidelity and adherence to SR processes. More recently, researchers have increasingly turned to artificial intelligence-based (AI) software to expedite the screening process. This paper evaluated the accuracy and usabiity of a novel, machine learning program, Sciome SWIFT-ActiveScreener (ActiveScreener) in a large SR of mental health outcomes following treatment for PTSD. ActiveScreener exceeded the expected 95% accuracy of the program to predict inclusion or exclusion of relevant articles, and was reported to be user friendly by both novice and seasoned screeners. Our results showed that ActiveScreener, when used appropriately, may save considerable time and human resources when performing SR.
Epidemiology of Congenital Heart Disease in Qatar: Preliminary findings from the Sidra Medicine Cardiac Registry
Authors: Almasri Muna , Al-Sulaiti Khalifa , Al Sayegh Dana , Sharma Omna , El Jerbi Aya , Al-Riyami Zakariya , Sarada Padma Kumari , Gupta Samir , Al-Saloos Hesham , Manyama Mange , Al-Shafai Kholoud N.
Published: August 2023

Background

Congenital heart disease (CHD) is one of the most common congenital anomalies in newborns. The birth prevalence of CHD across the world is variable, reflecting differences in diagnostic capabilities as well as environmental and/or genetic risk factors between regions. Here, we aim to determine the epidemiology of CHD in Qatar in terms of the magnitude, subtypes, associated risk factors and complications.

Methods and results

Data for 76 subjects with CHD were extracted from the Sidra cardiac registry database in October 2022. Extracted information for each subject included on age, nationality, gender, CHD diagnosis, outcomes of CHD, and comorbidities. Maternal history for some of the risk factors were also obtained from the registry. Statistical analysis was performed using Chi-Square tests and Fisher’s Exact tests.

Most of the subjects were from the Middle East and North Africa (MENA) region (52.6%), followed by Southeast Asian (30.3%) and Qatari (14.5%). The three most common CHD types were ventricular septal defect (VSD), Atrial septal defect (ASD), and Transposition of the great arteries (TGA). About 32% subjects were born by parents who are first-degree cousins. This association was statistically significant (P<0.05). About 6.9% subjects in this cohort were born to mothers who had Pre-Gestational Diabetes Mellitus.

Conclusion

The most common CHD type in this study was VSD followed by ASD. The rate of parental consanguinity was generally high among patients with CHDs. The pattern of non-genetic risk factors, comorbidities, and outcomes in patients with CHD was similar to those previously reported in other studies.

Clinical perspective

Congenital heart diseases and other birth defects are largely understudied in Qatar. This study provides epidemiological characteristics of patients with congenital heart diseases in Qatar.

A significant number of subjects in this study had multiple CHD lesions.

This study highlights the association between parental consanguinity and the increased incidence of congenital heart diseases in Qatar, a country with a high rate of parental consanguinity.

Majority of the subjects in this study underwent surgical intervention, perhaps reflecting the complexity of the CHD lesions.
Cellular and molecular basis of leptin resistance
Authors: Tan Bowen , Hedbacker Kristina , Kelly Leah , Zhang Zhaoyue , Luo Ji-Dung , Rabinowitz Joshua D. , Friedman Jeffrey M.
Published: August 2023

Obese humans and diet induced obese mice (DIO) have high leptin levels and fail to respond to the exogenous hormone suggesting that obesity is caused by leptin resistance, the pathogenesis of which is unknown. We found that leptin treatment reduced plasma levels of mTOR ligands leading us to hypothesize that mTOR activation might inhibit leptin signaling. Rapamycin, an mTOR inhibitor, reduced fat mass and increased leptin sensitivity in DIO mice but not in mice with defects in leptin signaling. Rapamycin restored leptin’s actions on POMC neurons but failed to reduce the weight of mice with defects in melanocortin signaling. mTOR activation in POMC neurons caused leptin resistance while POMC specific mutations in mTOR activators decreased the weight gain of DIO mice. Thus increased mTOR activity in POMC neurons is necessary and sufficient for the development of leptin resistance in DIO mice establishing a key pathogenic mechanism leading to obesity.