bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning–based biomarker profile derived from 4210 serially measured proteins predicts clinical outcome of patients with heart failure
Authors: de Bakker Marie , Petersen Teun B , Rueten-Budde Anja J , Akkerhuis K Martijn , Umans Victor A , Brugts Jasper J , Germans Tjeerd , Reinders Marcel J T , Katsikis Peter D , van der Spek Peter J , Ostroff Rachel , She Ruicong , Lanfear David , Asselbergs Folkert W , Boersma Eric , Rizopoulos Dimitris , Kardys Isabella
Published: October 2023

Aims

Risk assessment tools are needed for timely identification of patients with heart failure (HF) with reduced ejection fraction (HFrEF) who are at high risk of adverse events. In this study, we aim to derive a small set out of 4210 repeatedly measured proteins, which, along with clinical characteristics and established biomarkers, carry optimal prognostic capacity for adverse events, in patients with HFrEF.

Methods and results

In 382 patients, we performed repeated blood sampling (median follow-up: 2.1 years) and applied an aptamer-based multiplex proteomic approach. We used machine learning to select the optimal set of predictors for the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization). The association between repeated measures of selected proteins and PEP was investigated by multivariable joint models. Internal validation (cross-validated c-index) and external validation (Henry Ford HF PharmacoGenomic Registry cohort) were performed. Nine proteins were selected in addition to the MAGGIC risk score, N-terminal pro-hormone B-type natriuretic peptide, and troponin T: suppression of tumourigenicity 2, tryptophanyl-tRNA synthetase cytoplasmic, histone H2A Type 3, angiotensinogen, deltex-1, thrombospondin-4, ADAMTS-like protein 2, anthrax toxin receptor 1, and cathepsin D. N-terminal pro-hormone B-type natriuretic peptide and angiotensinogen showed the strongest associations [hazard ratio (95% confidence interval): 1.96 (1.17–3.40) and 0.66 (0.49–0.88), respectively]. The multivariable model yielded a c-index of 0.85 upon internal validation and c-indices up to 0.80 upon external validation. The c-index was higher than that of a model containing established risk factors (P = 0.021).

Conclusion

Nine serially measured proteins captured the most essential prognostic information for the occurrence of adverse events in patients with HFrEF, and provided incremental value for HF prognostication beyond established risk factors. These proteins could be used for dynamic, individual risk assessment in a prospective setting. These findings also illustrate the potential value of relatively ‘novel’ biomarkers for prognostication.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 24
Strategic Campaign Communication: Evidence from 30,000 Candidate Manifestos
Authors: Le Pennec Caroline
Published: October 2023

Politicians seeking to persuade voters may not always be able to say what they would like to say. Adopting policy positions opposite to that of their party or contradicting their previous policy announcements may be costly. I use computational text analysis on 30,000 candidate manifestos from two-round French elections to show that politicians take these costs into account, by toeing the party line and sticking to their platform, while also strategically adjusting their campaign communication and advertising neutral non-policy issues when they need to reach a broader electorate. I provide suggestive evidence that this moderation of electoral discourse predicts better performance in office and may therefore provide valuable information to voters.
Blood DNA methylation signature of diet quality and association with cardiometabolic traits
Authors: Domínguez-Barragán Jorge , Fernández-Sanlés Alba , Hernáez Álvaro , Llauradó-Pont Joana , Marrugat Jaume , Robinson Oliver , Tzoulaki Ioanna , Elosua Roberto , Lassale Camille
Published: October 2023

Aims

Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aims were to identify cytosine–phosphate–guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm) and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D), and coronary heart disease (CHD).

Methods and results

Meta-EWAS including 5274 participants in four cohorts from Spain, the USA, and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet, to a healthy plant-based diet, and to the Dietary Approaches to Stop Hypertension. Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. We found 18 differentially methylated CpGs associated with dietary scores (P < 1.08 × 10−7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI and at cg05399785 (WDR8) with greater SBP, and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk, and CHD risk and at cg0557921 (AHRR) with lower CHD risk.

Conclusion

Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.
Beneficial Effect of Societal Factors on APOE-ε2 and ε4 Carriers’ Brain Health: A Systematic Review
Authors: Aravena José M , Lee Jakyung , Schwartz Anna E , Nyhan Kate , Wang Shi-Yi , Levy Becca R
Published: October 2023

Background

Apolipoprotein-E (APOE) ε4 and ε2 are the most prevalent risk-increasing and risk-reducing genetic predictors of Alzheimer’s disease, respectively. However, the extent to which societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on brain health has not yet been examined systematically.

Methods

To fill this gap, we conducted a systematic review searching for studies in MEDLINE, Embase, PsycINFO, and Scopus until June 2023, that included: (a) 1 of 5 social determinants of health (SDH) identified by Healthy People 2030, (b) APOE-ε2 or APOE-ε4 allele carriers, (c) cognitive or brain-biomarker outcomes, and (d) studies with an analysis of how APOE-ε2 and/ or APOE-ε4 carriers differ on outcomes when exposed to SDH.

Results

From 14 076 articles retrieved, 124 met the inclusion criteria. In most of the studies, exposure to favorable SDH reduced APOE-ε4’s detrimental effect and enhanced APOE-ε2’s beneficial effect on cognitive and brain-biomarker outcomes (cognition: 70.5%, n: 74/105; brain-biomarkers: 71.4%, n: 20/28). A similar pattern of results emerged in each of the 5 Healthy People 2030 SDH categories, where finishing high school, having resources to satisfy basic needs, less air pollution, less negative external stimuli that can generate stress (eg, negative age stereotypes), and exposure to multiple favorable SDH were associated with better cognitive and brain health among APOE-ε4 and APOE-ε2 carriers.

Conclusions

Societal factors can reduce the harmful impact of APOE-ε4 and enhance the beneficial impact of APOE-ε2 on cognitive outcomes. This suggests that plans to reduce dementia should include community-level policies promoting favorable SDH.
Macrophage N-glycan processing inhibits antibody-dependent cellular phagocytosis
Authors: Díaz de león Jesús S Aguilar , Aguilar Isaac , Barb Adam W
Published: October 2023

Factors regulating macrophage effector function represent potential targets to optimize the efficacy of antibody-mediated therapies. Macrophages are myeloid cells capable of engulfing and destroying diseased or damaged target cells. Antibodies binding to the target cell surface can engage macrophage Fc gamma receptors (FcγRs) to elicit antibody-dependent cellular phagocytosis (ADCP), a process that contributes to treatments mediated by anti-tumor antibodies. Conversely, macrophage ADCP of apoptotic T cells is also linked to tolerance in the tumor environment. Here we evaluated the role of asparagine(N)-linked glycans in the function of macrophages derived from primary human monocytes. Macrophages treated with kifunensine, an inhibitor of N-glycan processing, exhibited greater target binding and ADCP of antibody-coated target cells. Kifunensine treatment increased ADCP of both rituximab-coated Raji B cells and trastuzumab-coated SKBR3 cells. ADCP required FcγRs; inhibiting CD64 / FcγRI led to the greatest reduction, followed by CD32 / FcγRII and then CD16 / FcγRIII in most donors. Kifunensine treatment also increased the antibody-binding affinity of CD16. Differences in the abundance of phosphorylated immune receptors, including Siglec-9, CD32a, and LAIR-1 correlated with the increased ADCP. These results demonstrate that N-glycan processing regulates macrophage effector function.
Redefining Patent Translation: The Influence of ChatGPT and the Urgency to Align Patent Language Regimes in Europe with Progress in Translation Technology
Authors: Larroyed Aline
Published: October 2023

This article investigates the impact of ChatGPT on the current language regimes in Europe for patent translation. With the growing number of patent applications being filed annually, there is a high demand for cost-effective and high-quality patent translation services. Despite advancements in translation technology, including ChatGPT, there remains a scarcity of research on the use of these technologies in patent translation, particularly with regard to the legal validity of machine-generated translations. The article takes an interdisciplinary approach, incorporating a review of regulatory documents, a preliminary evaluation of ChatGPT’s performance using the LISA QA matrix and a review of relevant doctrinal literature. The regulatory examination in this study centers on the provisions of the European Patent Convention and related legal documents that specify the language criteria for acquiring a patent within Europe. The preliminary evaluation uses a sample of 20 patents translated from English into Portuguese to assess accuracy, fluency and acceptability. The examination of available legal literature strives to attain a thorough comprehension of how laws and principles of the legal system are being put into practice in association with the progression of translation technologies. This article endeavors to examine the potential effects of utilizing ChatGPT in patent translation on existing language regulations in Europe and if new regulations will be necessary. It highlights the need for further research in this field to better understand the advantages and implications of using advanced language models in patent translation.
Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study
Authors: Garchitorena Andres , Rasoloharimanana Lova Tsikiniaina , Rakotonanahary Rado Jl , Evans Michelle V , Miller Ann C , Finnegan Karen E , Cordier Laura F , Cowley Giovanna , Razafinjato Benedicte , Randriamanambintsoa Marius , Andrianambinina Samuel , Popper Stephen J , Hotahiene Raphaël , Bonds Matthew H , Schoenhals Matthieu
Published: October 2023

Introduction

Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the World Health Organization Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021.

Methods

We integrated a nested seroprevalence study within a pre-existing longitudinal cohort conducted in a representative sample of 1600 households in Ifanadiana District, Madagascar. Socio-demographic and health information was collected in combination with dried blood spots for about 6500 individuals of all ages, which were analysed to detect IgG and IgM antibodies against four specific proteins of SARS-CoV-2 in a bead-based multiplex immunoassay. We evaluated spatio-temporal patterns in COVID-19 infection history and its associations with several geographic, socio-economic and demographic factors via logistic regressions.

Results

Eighteen percent of people had been infected by April-June 2021, with seroprevalence increasing with individuals’ age. COVID-19 primarily spread along the only paved road and in major towns during the first epidemic wave, subsequently spreading along secondary roads during the second wave to more remote areas. Wealthier individuals and those with occupations such as commerce and formal employment were at higher risk of being infected in the first wave. Adult mortality increased in 2020, particularly for older men for whom it nearly doubled up to nearly 40 deaths per 1000. Less than 10% of mortality in this period would be directly attributed to COVID-19 deaths if known infection fatality ratios are applied to observed seroprevalence in the district.

Conclusion

Our study provides a very granular understanding on COVID-19 transmission and mortality in a rural population of sub-Saharan Africa and suggests that the disease burden in these areas may have been substantially underestimated.
A many-objective evolutionary algorithm with population preprocessing and projection distance-assisted elimination mechanism
Authors: Wei Li-sen , Li Er-chao
Published: October 2023

Pareto dominance-based many-objective evolutionary algorithms (MaOEAs) face a significant challenge from many-objective problems (MaOPs). The selection pressure reduces as the number of objectives rises, while the non-dominated solution grows exponentially. Pareto dominance-based MaOEA increases the selection pressure by designing diversity-related environmental strategies. However, it still struggles to strike a good balance between population diversity and convergence. Moreover, the diversity-selection method increases the likelihood that dominance-resistant solutions (DRSs) will be chosen, which is detrimental to the performance of MaOEAs. To address the aforementioned problems, a many-objective optimization algorithm based on population preprocessing and projection distance-assisted elimination mechanism (PPEA) is proposed. In PPEA, first, the population preprocessing method is designed to lessen the negative impacts of DRSs. Second, to further improve the ability to balance population diversity and convergence of Pareto dominance-based MaOEAs, a projection distance-assisted elimination mechanism is proposed to remove the poorer individuals one by one until the population size satisfies the termination condition. The performance of PPEA was compared with seven excellent MaOEAs on a series of benchmark problems with 3–15 objectives and a real-world application problem. The experimental results indicate that PPEA is competitive and can effectively balance the diversity and convergence of the population when dealing with MaOPs.
A highly contiguous genome assembly for the pocket mouse Perognathus longimembris longimembris
Authors: Kozak Krzysztof M , Escalona Merly , Chumchim Noravit , Fairbairn Colin , Marimuthu Mohan P A , Nguyen Oanh , Sahasrabudhe Ruta , Seligmann William , Conroy Chris , Patton James L , Bowie Rauri C K , Nachman Michael W
Published: October 2023

The little pocket mouse, Perognathus longimembris, and its nine congeners are small heteromyid rodents found in arid and seasonally arid regions of Western North America. The genus is characterized by behavioral and physiological adaptations to dry and often harsh environments, including nocturnality, seasonal torpor, food caching, enhanced osmoregulation, and a well-developed sense of hearing. Here we present a genome assembly of Perognathus longimembris longimembris generated from PacBio HiFi long read and Omni-C chromatin-proximity sequencing as part of the California Conservation Genomics Project. The assembly has a length of 2.35 Gb, contig N50 of 11.6 Mb, scaffold N50 of 73.2 Mb, and includes 93.8% of the BUSCO Glires genes. Interspersed repetitive elements constitute 41.2% of the genome. A comparison with the highly endangered Pacific pocket mouse, P. l. pacificus, reveals broad synteny. These new resources will enable studies of local adaptation, genetic diversity, and conservation of threatened taxa.
Clinical characterization of patients with gBRCA1/2 mutation-positive unresectable pancreatic cancer: a multicenter prospective study
Authors: Kubo Tomohiro , Muramatsu Joji , Arihara Yohei , Murota Ayako , Ishikawa Kazuma , Yoshida Makoto , Nagashima Hiroyuki , Tamura Fumito , Ikeda Yuki , Usami Makoto , Ono Michihiro , Nakamura Hajime , Watanabe Daichi , Shibata Takanori , Kasahara Kaoru , Sakurai Akihiro , Takada Kohichi
Published: October 2023

Background

Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan.

Methods & Results

In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0–9.2).

Conclusions

The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.

An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.
Phase retrieval of electron rocking curves using total variation and total squared variation regularizations
Authors: Shichi Akihiro , Ishizuka Hiroyuki , Saitoh Koh
Published: October 2023

In this study, a new method for the phase retrieval of electron rocking curves observed using convergent-beam electron diffraction, which is applicable to the determination of three-dimensional lattice displacement fields along the beam direction, is proposed. Total variation and total squared variation regularizations are introduced for phase retrieval to suppress overfitting to noise or background signals in the rocking curves and to reproduce the sparse characteristics of displacement fields, which exist only near lattice defects. The results show that the proposed algorithm is effective for rocking curves modulated by the dynamical effect of electron diffraction. The accuracy of phase reconstruction using the proposed method is also discussed. Phase retrieval of the experimental rocking curves obtained from a stacking fault in stainless steel is demonstrated.
Individual-level home values and cancer mortality in a statewide registry
Authors: Zhu Alec , Rhodes Stephen , Dong Weichuan , Rose Johnie , Cullen Jennifer , Miller David B , Spratt Daniel E , Ponsky Lee , Shoag Daniel , Trapl Erika , Schumacher Fredrick , Penukonda Suhas , Brant Aaron , Strasser Mary O , Koroukian Siran M , Markt Sarah , Shoag Jonathan E
Published: October 2023

Background

Prior work assessing disparities in cancer outcomes has relied on regional socioeconomic metrics. These metrics average data across many individuals, resulting in a loss of granularity and confounding with other regional factors.

Methods

Using patients’ addresses at the time of diagnosis from the Ohio Cancer Incidence Surveillance System, we retrieved individual home price estimates from an online real estate marketplace. This individual-level estimate was compared with the Area Deprivation Index (ADI) at the census block group level. Multivariable Cox proportional hazards models were used to determine the relationship between home price estimates and all-cause and cancer-specific mortality.

Results

A total of 667 277 patients in Ohio Cancer Incidence Surveillance System were linked to individual home prices across 16 cancers. Increasing home prices, adjusted for age, stage at diagnosis, and ADI, were associated with a decrease in the hazard of all-cause and cancer-specific mortality (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.92 to 0.93, and HR = 0.95, 95% CI = 0.94 to 0.95, respectively). Following a cancer diagnosis, individuals with home prices 2 standard deviations above the mean had an estimated 10-year survival probability (7.8%, 95% CI = 7.2% to 8.3%) higher than those with home prices 2 standard deviations below the mean. The association between home price and mortality was substantially more prominent for patients living in less deprived census block groups (Pinteraction < .001) than for those living in more deprived census block groups.

Conclusion

Higher individual home prices were associated with improved all-cause and cancer-specific mortality, even after accounting for regional measures of deprivation.
Beyond research as a dirty word? Searching for ethical and reflexive ways of doing research with and for migrant communities
Authors: Fiorito Tara
Published: October 2023

What do “white” migration researchers, such as myself, need to learn from over-researched (undocumented) migrant youth and indigenous communities that consider research a dirty word? And how do such assertions not lead to an impasse, but can actually enable scholars to conduct ethical and reflexive research that directly engages and benefits migrant communities throughout the research process? These are the central questions I seek to take up in this article by critically reflecting on my engaged research with undocumented migrant youth (activists) in Los Angeles and the Netherlands. Building on epistemological and ethical considerations and practices from participatory action research, co-creative research, and arts-based research, this article argues for four essential shifts in our modes of knowledge production, which are then empirically illustrated through a critical examination of my own research. These four shifts are: (1) a move from epistemic violence and injustice to epistemic justice, (2) a move from damage-centred to desire-based research, (3) a move from singular to comprehensive narratives, and (4) a move from extractavist to engaged research.
Selection on Visual Opsin Genes in Diurnal Neotropical Frogs and Loss of the SWS2 Opsin in Poison Frogs
Authors: Wan Yin Chen , Navarrete Méndez María José , O'Connell Lauren A , Uricchio Lawrence H , Roland Alexandre-Benoit , Maan Martine E , Ron Santiago R , Betancourth-Cundar Mileidy , Pie Marcio R , Howell Kimberly A , Richards-Zawacki Corinne L , Cummings Molly E , Cannatella David C , Santos Juan C , Tarvin Rebecca D
Published: October 2023

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here, we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae: Atelopus), and pumpkin toadlets (Brachycephalidae: Brachycephalus). We found evidence of positive selection on 44 amino acid sites in LWS, SWS1, SWS2, and RH1 opsin genes, of which one in LWS and two in RH1 have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence that SWS2, normally expressed in rod cells in frogs and some salamanders, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their behavior. Our analyses show that assessments of opsin diversification in across taxa could expand our understanding of the role of sensory system evolution in ecological adaptation.
Tubular toxicity of proteinuria and the progression of chronic kidney disease
Authors: Makhammajanov Zhalaliddin , Gaipov Abduzhappar , Myngbay Askhat , Bukasov Rostislav , Aljofan Mohamad , Kanbay Mehmet
Published: October 2023

Proteinuria is a well-established biomarker of chronic kidney disease (CKD) and a risk predictor of associated disease outcomes. Proteinuria is also a driver of CKD progression toward end-stage kidney disease. Toxic effects of filtered proteins on proximal tubular epithelial cells enhance tubular atrophy and interstitial fibrosis. The extent of protein toxicity and the underlying molecular mechanisms responsible for tubular injury during proteinuria remain unclear. Nevertheless, albumin elicits its toxic effects when degraded and reabsorbed by proximal tubular epithelial cells. Overall, healthy kidneys excrete over 1000 individual proteins, which may be potentially harmful to proximal tubular epithelial cells when filtered and/or reabsorbed in excess. Proteinuria can cause kidney damage, inflammation and fibrosis by increasing reactive oxygen species, autophagy dysfunction, lysosomal membrane permeabilization, endoplasmic reticulum stress and complement activation. Here we summarize toxic proteins reported in proteinuria and the current understanding of molecular mechanisms of toxicity of proteins on proximal tubular epithelial cells leading to CKD progression.
Statin therapy and the incidence of atherosclerotic cardiovascular events after kidney transplantation
Authors: Nazoiri Charifa , Liabeuf Sophie , Brazier François , Nowak Alban , Bennis Youssef , Laville Solène M , Bodeau Sandra , Gras-Champel Valérie , Masmoudi Kamel , Choukroun Gabriel , Batteux Benjamin
Published: October 2023

Background

Statins are recommended in kidney transplant recipients (KTRs)—a population with a high risk of major cardiovascular (CV) events. However, the literature data on the effectiveness of statins in KTRs are sparse and inconclusive. The present study's objective was to evaluate the association between statin exposure and atherosclerotic CV events in KTRs and the biochemical effectiveness of statins on the lipid profile.

Methods

A total of 318 consecutive KTRs managed at a single center between 2006 and 2019 were retrospectively included. Those exposed to statins after transplantation were incident users. In all users, statins were indicated for primary CV prevention. Lipid profiles, the occurrence of any atherosclerotic CV events (stroke, myocardial infarction, other atherosclerotic CV events and atherosclerotic CV deaths) were documented comprehensively. We applied Cox models that included statin exposure as a time-dependent covariate fitted with time-varying inverse probability treatment weighting (IPTW) to assess the effectiveness of statins on atherosclerotic CV events and on all CV events. We built linear mixed models to assess the biochemical effectiveness of statins.

Results

During a median (interquartile range) follow-up period of 6.0 (3.9–10.0) years, 27 atherosclerotic CV events occurred in 26 patients. In the Cox models fitted with time-varying IPTW, exposure to statins was not associated with a decrease in atherosclerotic CV events; the hazard ratio was 1.16 (95% confidence interval 0.53–2.53) (P = .700). In the linear mixed models, statin exposure was associated with significant decrease over time in triglyceride and low-density lipoprotein cholesterol concentrations (P < .001). These results were consistent when stratified for the intensity of statin therapy.

Conclusion

Even though the lipid profile improved, statin exposure was not associated with a decrease in CV events in this real-life, single-center, retrospective, long-term follow-up study of a KTR cohort. Larger, controlled studies are needed to confirm or refute these results.
Designing artificial ion channels with strict K+/Na+ selectivity toward next-generation electric-eel-mimetic ionic power generation
Authors: Li Jipeng , Du Linhan , Kong Xian , Wu Jianzhong , Lu Diannan , Jiang Lei , Guo Wei
Published: October 2023

A biological potassium channel is >1000 times more permeable to K+ than to Na+ and exhibits a giant permeation rate of ∼108 ions/s. It is a great challenge to construct artificial potassium channels with such high selectivity and ion conduction rate. Herein, we unveil a long-overlooked structural feature that underpins the ultra-high K+/Na+ selectivity. By carrying out massive molecular dynamics simulation for ion transport through carbonyl-oxygen-modified bi-layer graphene nanopores, we find that the twisted carbonyl rings enable strict potassium selectivity with a dynamic K+/Na+ selectivity ratio of 1295 and a K+ conduction rate of 3.5 × 107 ions/s, approaching those of the biological counterparts. Intriguingly, atomic trajectories of K+ permeation events suggest a dual-ion transport mode, i.e. two like-charged potassium ions are successively captured by the nanopores in the graphene bi-layer and are interconnected by sharing one or two interlayer water molecules. The dual-ion behavior allows rapid release of the exiting potassium ion via a soft knock-on mechanism, which has previously been found only in biological ion channels. As a proof-of-concept utilization of this discovery, we propose a novel way for ionic power generation by mixing KCl and NaCl solutions through the bi-layer graphene nanopores, termed potassium-permselectivity enabled osmotic power generation (PoPee-OPG). Theoretically, the biomimetic device achieves a very high power density of >1000 W/m2 with graphene sheets of <1% porosity. This study provides a blueprint for artificial potassium channels and thus paves the way toward next-generation electric-eel-mimetic ionic power generation.
The Race Politics Associated With Wearing a Mask in Public to Combat COVID-19
Authors: Sanchez Gabriel R , Vargas Edward D , Dominguez Melanie Sayuri
Published: October 2023

We explore the racial and ethnic politics associated with mask wearing early in the COVID-19 pandemic. Using panel and cross-sectional data from the National Panel Study of COVID-19 (n = 1,996) fielded in March and April 2020, we asked Americans about their self-reported race/ethnicity, their political party affiliation, and if they have worn a mask or scarf in public to stop the spread of the coronavirus. We also asked respondents who reported wearing a mask in public if they worry they might be mistaken for a criminal. Our logistic regression models found that racial and ethnic minorities are more likely to wear a mask or scarf over their faces to prevent the spread of COVID-19 despite being more likely to worry about being criminalized by police or security while wearing a mask. We argue that proximal contact with the virus, because racial and ethnic minorities are more likely to be affected by COVID-19, leads to increased willingness by people in these groups to protect themselves and others. Democrats were also more likely to wear masks compared with Republican respondents. and those living in Republican-led states were less likely to wear a mask in public and more likely to be criminalized for wearing a mask.

Was mask use during the early COVID-19 pandemic political? In our paper, we use panel and cross-sectional data from the National Panel Study of COVID-19 fielded in March and April 2020 when we asked Americans whether they had worn masks. We also asked those who wore a mask if they felt criminalized while wearing a mask. Our findings show that there are stark differences in mask use between demographic groups and worrying about being criminalized while wearing one.
Circadian misalignment impacts the association of visceral adiposity with metabolic syndrome in adolescents
Authors: Morales-Ghinaglia Natasha , He Fan , Calhoun Susan L , Vgontzas Alexandros N , Liao Jason , Liao Duanping , Bixler Edward O , Fernandez-Mendoza Julio
Published: October 2023

Study Objectives

Although insufficient sleep is a risk factor for metabolic syndrome (MetS), the circadian timing of sleep (CTS) is also involved in cardiac and metabolic regulation. We examined whether delays and deviations in the sleep midpoint (SM), a measure of CTS, modify the association between visceral adipose tissue (VAT) and MetS in adolescents.

Methods

We evaluated 277 adolescents (median 16 years) who had at least 5 nights of at-home actigraphy (ACT), in-lab polysomnography (PSG), dual-energy X-ray absorptiometry (DXA) scan, and MetS score data. Sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL) were examined as effect modifiers of the association between VAT and MetS, including waist circumference, blood pressure, insulin resistance, triglycerides, and cholesterol. Linear regression models adjusted for demographics, ACT-sleep duration, ACT-sleep variability, and PSG-apnea–hypopnea index.

Results

The association between VAT and MetS was significantly stronger (p-values for interactions < 0.001) among adolescents with a schooldays SM later than 4:00 (2.66 [0.30] points increase in MetS score), a SI higher than 1 hour (2.49 [0.30]) or a SJL greater than 1.5 hours (2.15 [0.36]), than in those with an earlier SM (<3:00; 1.76 [0.28]), lower SI (<30 minutes; 0.98 [0.70]), or optimal SJL (<30 minutes; 1.08 [0.45]).

Conclusions

A delayed sleep phase, an irregular sleep–wake cycle, and greater social jetlag on schooldays identified adolescents in whom VAT had a stronger association with MetS. Circadian misalignment is a risk factor that enhances the impact of visceral obesity on cardiometabolic morbidity and should be a target of preventative strategies in adolescents.
Guernsey Royal Court finds a dishonest breach of trust: acting ‘en bon père de famille’
Authors: Lyne Sandie , Parr Gareth , Randall Victoria
Published: October 2023

In handing down its judgment in the matter of Nina Naustdal v TKC Corporate Services NV and two others on 23 December 2022, the Royal Court of Guernsey found that the First Defendant, a professional trustee, had acted in dishonest breach of trust. At the heart of the judgment was that the principal asset of the Trust had been transferred out of trust to benefit a stranger to the trust, constituting a fraud on a power. Amongst the various other relief that it granted, the Court declared that the purported transfer of trust property by the trustee was void. Furthermore, it ordered that the trustee be deprived of its indemnity for any legal fees and disbursements in connection with the proceedings and to repay any sums that had been taken from the trust.
Colorectal cancer hepatic metastases resection margins outcomes: a single-centre retrospective cohort study
Authors: Marion Samuel , Facchino Sabrina , Cheng-Oviedo Sonia , Collin Yves
Published: October 2023

Background:

Surgical resection is the most efficient treatment for isolated colorectal cancer hepatic metastases. Among the known prognostic factors of this procedure, the impact of the resection margin width is still a controversial matter in the literature.

Methods:

A retrospective cohort study was performed including 170 patients who underwent surgical resection of colorectal cancer liver metastases (CRLMs) between 2006 and 2016 in our hepatobiliary unit. Resection margin width was determined histologically by measuring the distance from the tumour in millimetres or centimetres. Patients’ clinical characteristics were also collected. Patients were then stratified in two tumour margin groups: below 5 mm (group A) and equal to or above 5 mm (group B). Overall survival (OS) and disease-free survival (DFS) were the primary outcomes.

Results:

Kaplan–Meier curves showed significantly better outcomes for cases having resection margins above 5 mm for both DFS with 1508.7 days (range 1151.2–1866.2) in group A, compared to 2463.9 days (range 2021.3–2906.5) in group B (P=0.049), and OS with 1557.8 days (range 1276.3–1839.3) for group A and 2303.8 days (range 1921.2–-2686.4) for group B (P=0.020). This survival benefit was not significant for patients presenting with stage IV CRC at diagnosis or cases where extended (7+ segments) resections were performed.

Conclusion:

Five-millimetre margins provide a significant survival advantage and should be aimed for in the treatment of CRLMs. Further research on the cause for this finding, including tumour biology’s impact on survival, is required.
Induction of Brugada electrocardiogram pattern with aluminum phosphide poisoning: a case report
Authors: Allam Parbej , Shakya Smriti , Yadav Vijay , KC Shradha , Sedai Hari , Poddar Elisha , Shrestha Suraj , KC Niranjan , Mahato Arun Kumar
Published: October 2023

Introduction and importance:

Aluminum phosphide (ALP) is a commonly used suicidal agent in an agrarian country like Nepal. The unmasking of the Brugada pattern in the electrocardiogram (ECG) associated with ALP poisoning is a rare phenomenon, and studies pertaining to it are scarce in the medical literature.

Case presentation:

An 18-year-old female presented to the emergency department with multiple episodes of vomiting, headache, blurring of vision, and abdominal pain after 4 h of consumption of ALP with suicidal intent. A 12-lead ECG revealed a coved ST-segment elevation and T-wave inversion in leads V1–V3 with right bundle branch block suggestive of a type 1 Brugada pattern. Her past medical and family history was not significant. The patient made an uneventful recovery with the required supportive treatments.

Clinical discussion:

Cardiac arrhythmias are the major cause of death in ALP poisoning. Unmasking of the Brugada ECG pattern is a rare but potentially fatal complication implicated in various pharmacological toxicities, including tricyclic antidepressants, cocaine, procainamide, disopyramide, flecainide, and rarely with ALP.

Conclusions:

ALP poisoning can unmask the Brugada ECG pattern, which can lead to ventricular fibrillation and/or sudden cardiac death.
Factors influencing refusal of lumbar puncture in children under age 10: a cross-sectional study
Authors: Masood Shaheen , Farrukh Riffat , Naseer Amber , Saqib Muhammad , Kadri Adeel , Shakoor Ibrahim , Mustafa Sultan , Mumtaz Hassan
Published: October 2023

Background:

This study aimed to investigate the factors associated with refusal of lumbar puncture (LP) in children aged 1–10 years who presented to a paediatric department in our hospital.

Methods:

A sample of parents and guardians of children who presented to the paediatric department were surveyed to gather information about their educational background and decision-making processes. Attending doctors were also interviewed using a questionnaire to gather their perspectives on the reasons for LP refusal in children. Attending doctors then tried to convince the parents or guardians to see if it changed their decision.

Results:

The study found that the majority of parents and guardians had a lower educational background, with over half being illiterate. Refusal of LP was seen most frequently in parents or guardians who were illiterate. The decision-making process was found to be heavily dependent on the father in a male-dominated society. Peer pressure and lack of knowledge were found to be factors that contributed to LP refusal.

Conclusion:

Refusal of a LP was linked to having a lower educational background and to societal influences in this cross-sectional study of children aged 1–10 years. More than half of the parents and guardians were illiterate, indicating that they had a lower level of education. Refusing LP was influenced by a number of factors, including social pressure and a lack of information. However, these obstacles were overcome thanks to the efforts of the attending doctors who dispelled myths and reassured the parents and guardians of the necessity and safety of the procedure. Possible roadblocks include a lack of financial resources and common misconceptions about LP. These results highlight the significance of addressing educational and societal factors to enhance children’s healthcare.
The tendency of segmental distribution of hepatic metastasis according to couinaud classification: a comparison of portal versus systemic route of metastatis due to primary colorectal and breast tumors
Authors: Khan Dawar , Khan Ayimen Khalid , Khan Sarim Dawar , Aman Muhammad , Amin Ahsun , Waseem Maria , Kumari Usha , Khan Faheemullah , Pervez Alina , Khan Aarash
Published: October 2023

Objective:

The liver is the commonest site of metastatic disease for patients with colorectal cancer (CRC), with at least 25% of patients developing liver metastasis (LM) during their illness. About 50% of patients diagnosed with metastatic breast cancer develop LM, and 5–12% of these patients develop LM as the main site of breast cancer recurrence. This study aims to determine the frequency of segmental distribution of LM seeding from portal versus systemic routes of dissemination due to primary CRC and breast carcinoma, respectively.

Material and methods:

This retrospective study was conducted in a tertiary care teaching hospital in Pakistan. Ethical approval was taken from the institutional review board. A total of 587 patients were included in the study with 297 CRC patients with LM and 300 breast carcinoma patients with LM. Segment I involvement was excluded from the calculation because of the dual blood supply. Patients’ detailed demographics and other information were collected on a predesigned proforma. The authors evaluated axial and multiplanar reformatted computed tomography images for LM and CRC metastasis. Data analysis was done using SPSS version 25. P value less than or equal to 0.05 was considered statistically significant.

Results:

A study population of 587 patients was employed that comprised 287 CRC and 300 breast carcinoma patients. There were 179 (30.5%) male and 408 (69.5%) female patients. The mean age of patients was 54.9±13.3. The study revealed that 204 (34.8%) CRC patients showed right lobe (V, VI, VII, VIII) and 83 (14.1%) CRC patients showed left lobe involvement of metastasis while 192 (32.7%) breast carcinoma patients showed right lobe involvement and 108 (18.4%) breast carcinoma patients showed left lobe involvement in metastasis (P=0.02). We also found 40 (6.8%) colorectal and 55 (9.4%) breast carcinoma patients showed left lateral segment (II, III) involvement. Medial segment involvement (IV) was seen in 43 (7.3%) CRC patients and 53 (9%) breast carcinoma patients (P=0.03).

Conclusion:

The right hepatic lobe is the predominant site of metastasis independent of the portal or systemic route of dissemination in primary carcinoma. Moreover, in left lobe metastasis medial segment (IV) is more affected in CRC while the lateral segment (II, III) is more affected in breast carcinoma.
Odds of HIV among incarcerated drug users: a systematic review and meta-analysis of Asian countries
Authors: Hussain Hassan ul , Kumar Kanwal Ashok , Rehan Syeda Tayyaba , Khan Zayeema , Hashmi Mahnoor Rehan , Khabir Yumna , Fatir Chaudhary Abdul , Tahir Muhammad Junaid , Ahmed Ali , Shrateh Oadi N. , Huda Md. Nazmul
Published: October 2023

Background:

HIV makes up a large portion of infectious diseases globally. People injecting drugs in prisons are at high risk for contracting HIV infection. Prisons house ~10.2 million people globally, making them a high-risk setting for HIV transmission. This systematic review summarizes the available data on the odds of developing HIV infection among imprisoned people who inject drugs (PWIDs) in Asian regions.

Methods:

The authors electronically assessed published studies from January, 2000 to December, 2022, including studies that investigated the odds of HIV in imprisoned PWIDs. We extensively searched PubMed, ERIC, and Cochrane Central and Google Scholar with no constraints in language or time. All the observational studies evaluating the chances of HIV in Asian prisoners with an exposure group of PWIDs and a control group of non-injecting-drug users were included in our analysis.

Results:

The databases search yielded 254 potential studies, 10 observational studies of which having a total of 17 333 participants were included. A low or moderate risk of bias was reported in all the studies except one case-control. The pooled analysis showed a significant association between PWIDs and the chances of contracting HIV infection (Odds ratio=6.40; 95% CI=3.89–10.52; P<0.00001; I2=53%).

Conclusion:

This study found a vital correlation between injecting-drug usage during imprisonment and HIV transmission speed. The results of this meta-analysis support the need to prevent HIV and conducting treatment programs in high-risk settings like prisons.