bluuebunny/crossref_metadata_2025 huggingface dataset:
Photonic band gaps and waveguide slow-light propagation in Bravais–Moiré two-dimensional photonic crystals
Authors: Gómez-Urrea H A , Cardona J G , Caro-Lopera F J , Mora-Ramos M E
Published: November 2022

Photonic band gap widths and slow-light optical guided modes are theoretically investigated for Bravais–Moiré (BM) photonic crystals (PCs) made of cylindrical dielectric cores which are formed from the combination of two square Bravais lattices. The Moiré pattern forms due to a commensurable rotation of one of these lattices with respect to the other. The analysis of gap maps is made versus the radii of dielectric cores—both rotated and unrotated—contained in the BM unit cell (UC). Guided modes are considered within the framework of coupled-resonator optical waveguides (CROWs), built from the generation of a point defect chain along the direction of electromagnetic wave propagation. For the analyzed structures, rather wide photonic band gaps were found. It was noticed that changing the core radii can significantly affect the dielectric contrast in the UC, leading to wider gaps. In addition, due to the kind of crystal cell structure considered, guided modes with group velocities smaller than those typically observed in PCs with simple square lattices were found for the investigated CROWs.
Photoelectron spectromicroscopy analysis of graphene during gate-controlled photo-oxidation process
Authors: Nagamura Naoka , Konno Shun , Matsumoto Morihiro , Zhang Wenxiong , Kotsugi Masato , Oshima Masaharu , Nouchi Ryo
Published: November 2022

The analysis of chemical reactions in two-dimensional (2D) materials is becoming increasingly important for device applications. Typically, 2D materials are in the form of small flakes; therefore, local inhomogeneities between or within the flakes should be investigated. In this study, we investigated the gate-controlled UV photo-oxidation reaction of monolayer graphene sheets using field-effect transistor structures. We performed a surface characterization of the photo-oxidized graphene micro-sheets using an original scanning photoelectron microscopy system that enables element-selective electronic and chemical state analysis with a high spatial resolution. We succeeded for the first time in experimentally revealing the progression of the photo-oxidation reaction in graphene from the edge. During the photo-oxidation process, hole doping from the adsorbed molecules occurred first. The reaction proceeded selectively to the edges of the graphene sheets. Defects were then introduced by chemical reactions with adsorbed molecules, and finally the graphene sheets decomposed and disappeared.
Chromosome size matters: genome evolution in the cyperid clade
Authors: Elliott Tammy L , Zedek František , Barrett Russell L , Bruhl Jeremy J , Escudero Marcial , Hroudová Zdenka , Joly Simon , Larridon Isabel , Luceño Modesto , Márquez-Corro José Ignacio , Martín-Bravo Santiago , Muasya A Muthama , Šmarda Petr , Thomas William Wayt , Wilson Karen L , Bureš Petr
Published: November 2022

Background and Aims

While variation in genome size and chromosome numbers and their consequences are often investigated in plants, the biological relevance of variation in chromosome size remains poorly known. Here, we examine genome and mean chromosome size in the cyperid clade (families Cyperaceae, Juncaceae and Thurniaceae), which is the largest vascular plant lineage with predominantly holocentric chromosomes.

Methods

We measured genome size in 436 species of cyperids using flow cytometry, and augment these data with previously published datasets. We then separately compared genome and mean chromosome sizes (2C/2n) amongst the major lineages of cyperids and analysed how these two genomic traits are associated with various environmental factors using phylogenetically informed methods.

Key Results

We show that cyperids have the smallest mean chromosome sizes recorded in seed plants, with a large divergence between the smallest and largest values. We found that cyperid species with smaller chromosomes have larger geographical distributions and that there is a strong inverse association between mean chromosome size and number across this lineage.

Conclusions

The distinct patterns in genome size and mean chromosome size across the cyperids might be explained by holokinetic drive. The numerous small chromosomes might function to increase genetic diversity in this lineage where crossovers are limited during meiosis.
Evaluation of tools for taxonomic classification of viruses
Authors: Cadenas-Castrejón Elizabeth , Verleyen Jérôme , Boukadida Celia , Díaz-González Lorena , Taboada Blanca
Published: November 2022

Viruses are the most abundant infectious agents on earth, and they infect living organisms such as bacteria, plants and animals, among others. They play an important role in the balance of different ecosystems by modulating microbial populations. In humans, they are responsible for some common diseases and may cause severe illnesses. Viral metagenomic studies have become essential and offer the possibility to understand and extend the knowledge of virus diversity and functionality. For these approaches, an essential step is the classification of viral sequences. In this work, 11 taxonomic classification tools were compared by analysing their performances, in terms of sensitivity and precision, to classify reads at the species and family levels using the same (viral and nonviral) datasets and evaluation metrics, as well as their processing times and memory requirements. The results showed that factors such as richness (numbers of viral species in samples), taxonomic level in the classification and read length influence tool performance. High values of viral richness in samples decreased the performances of most tools. Additionally, the classifications were better at higher taxonomic levels, such as families, compared to lower taxonomic levels, such as species, and were more evident in short reads. The results also indicated that BLAST and Kraken2 were the best tools for classifying all types of reads, while FastViromeExplorer and VirusFinder were only good when used for long reads and Centrifuge, DIAMOND, and One Codex when used for short reads. Regarding nonviral datasets (human and bacterial), all tools correctly classified them as nonviral.
Candesartan—the next anti-amyloid drug?
Authors: Yasar Sevil
Published: November 2022

This scientific commentary refers to ‘Safety and biomarker effects of candesartan in non-hypertensive adults with prodromal Alzheimer's disease’ by Hajjar et al. (https://doi.org/10.1093/braincomms/fcac270).
Selective attention sharpens population receptive fields in human auditory cortex
Authors: Lage-Castellanos Agustin , De Martino Federico , Ghose Geoffrey M , Gulban Omer Faruk , Moerel Michelle
Published: November 2022

Selective attention enables the preferential processing of relevant stimulus aspects. Invasive animal studies have shown that attending a sound feature rapidly modifies neuronal tuning throughout the auditory cortex. Human neuroimaging studies have reported enhanced auditory cortical responses with selective attention. To date, it remains unclear how the results obtained with functional magnetic resonance imaging (fMRI) in humans relate to the electrophysiological findings in animal models. Here we aim to narrow the gap between animal and human research by combining a selective attention task similar in design to those used in animal electrophysiology with high spatial resolution ultra-high field fMRI at 7 Tesla. Specifically, human participants perform a detection task, whereas the probability of target occurrence varies with sound frequency. Contrary to previous fMRI studies, we show that selective attention resulted in population receptive field sharpening, and consequently reduced responses, at the attended sound frequencies. The difference between our results to those of previous fMRI studies supports the notion that the influence of selective attention on auditory cortex is diverse and may depend on context, stimulus, and task.
The effects of bilateral posterior parietal cortex tRNS on reading performance
Authors: Bertoni Sara , Franceschini Sandro , Campana Gianluca , Facoetti Andrea
Published: November 2022

According to established cognitive neuroscience knowledge based on studies on disabled and typically developing readers, reading is based on a dual-stream model in which a phonological-dorsal stream (left temporo-parietal and inferior frontal areas) processes unfamiliar words and pseudowords, whereas an orthographic-ventral stream (left occipito-temporal and inferior frontal areas) processes known words. However, correlational neuroimaging, causal longitudinal, training, and pharmacological studies have suggested the critical role of visuo-spatial attention in reading development. In a double blind, crossover within-subjects experiment, we manipulated the neuromodulatory effect of a short-term bilateral stimulation of posterior parietal cortex (PPC) by using active and sham tRNS during reading tasks in a large sample of young adults. In contrast to the dual-stream model predicting either no effect or a selective effect on the stimulated phonological-dorsal stream (as well as to a general multisensory effect on both reading streams), we found that only word-reading performance improved after active bilateral PPC tRNS. These findings demonstrate a direct neural connectivity between the PPC, controlling visuo-spatial attention, and the ventral stream for visual word recognition. These results support a neurobiological model of reading where performance of the orthographic-ventral stream is boosted by an efficient deployment of visuo-spatial attention from bilateral PPC stimulation.
Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice
Authors: Li Lai-Fu , Li Zi-Lin , Song Bai-Lin , Jiang Yi , Wang Yan , Zou Hua-Wei , Yao Lun-Guang , Liu Ying-Juan
Published: November 2022

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant–subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.
Morphological characteristics of lesions with thin cap fibroatheroma—a substudy from the COMBINE (OCT-FFR) trial
Authors: Roleder-Dylewska Magda , Gasior Pawel , Hommels Tobias M , Roleder Tomasz , Berta Balasz , Ang Hui Ying , Ng Jaryl Chen Koon , Hermanides Renicus S , Fabris Enrico , IJsselmuiden Alexander J J , Kauer Floris , Alfonso Fernando , von Birgelen Clemens , Escaned Javier , Camaro Cyril , Kennedy Mark W , Pereira Bruno , Magro Michael , Nef Holger , Reith Sebastian , Malinowski Krzysztof , De Luca Giuseppe , Garcia Garcia Hector M , Granada Juan F , Wojakowski Wojciech , Kedhi Elvin
Published: November 2022

Aims

To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs).

Methods and results

From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area.

Conclusion

Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.
Discrimination driven by variation in social and economic conservatism: evidence from a nationwide field experiment
Authors: Lacroix Julie , Ruedin Didier , Zschirnt Eva
Published: November 2022

We examine how contextual variation in aggregated political attitudes shapes ethnic discrimination. Using a field experiment with national coverage we identify ethnic discrimination in the Swiss housing market (N = 7,533 queries for viewings from fictitious persons who vary by name to signal ethnic origin). We use referendums and popular initiatives to identify the aggregated political attitudes at the municipality level in two dimensions: social conservatism and economic conservatism. We show that although aggregated levels of discrimination are low, discrimination varies spatially – higher levels of discrimination are found in municipalities that are both socially and economically conservative. Municipalities that are economically conservative, but socially liberal also tend to exhibit ethnic discrimination. By contrast, we find no evidence of ethnic discrimination in municipalities that are socially conservative, but economically liberal. Considering how the literature highlights social conservatism when discussing the role of political ideology on attitudes and ethnic discrimination, this result highlights how differentiating different forms of conservatism helps better understand the relationship between ideology and behaviour – in this case ethnic discrimination.
Coronary microvascular dysfunction is associated with impaired cognitive function: the Cerebral-Coronary Connection study (C3 study)
Authors: Mejia-Renteria Hernan , Travieso Alejandro , Matías-Guiu Jordi A , Yus Miguel , Espejo-Paeres Carolina , Finocchiaro Francesca , Fernández Sara , Gomez-Escalonilla Carlos Ignacio , Reneses-Prieto Blanca , Gómez-Garré Maria Dulcenombre , Delgado-Alvarez Alfonso , Bustos Ana , Perez de Isla Leopoldo , de Diego Jose Juan Gomez , Modrego-Martin Javier , Ortega-Hernandez Adriana , Papadopoulos Petros , Arrazola-García Juan , Matías-Guiu Jorge , Escaned Javier
Published: November 2022

Background

It remains unknown whether the presence of coronary microcirculatory dysfunction (CMD) correlates with its equivalent condition in the brain, cerebral small vessel disease (CSVD). The cerebral-coronary connection (C3), a prospective blinded study, investigated the prevalence of CMD in patients with coronary artery disease (CAD) and its association with CSVD and cognitive function.

Methods and results

Patients with documented CAD fulfilling inclusion criteria underwent physiological assessment of epicardial vessels and the microcirculation using intracoronary pressure and Doppler. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperaemic microvascular resistance. Brain magnetic resonance imaging, transcranial Doppler (TCD), and neurocognitive examination were performed. Overall, 67 patients were included in the study (mean age 66 years, 73% female). Patients with abnormal CFR (<2.0) (55.2%) showed higher burden of white-matter hyperintensities: 43.2 vs. 20.0% (P = 0.044). After statistical adjustment, low CFR was associated with lower grey matter volume (P = 0.024) and with parameters of white-matter microstructural damage in diffusion-tensor imaging (lower fractional anisotropy and higher mean diffusivity, P = 0.029 and P = 0.032, respectively). Low CFR was associated with higher resistive (P = 0.027) and pulsatility (P = 0.043) values on TCD, and worse neurocognitive test scores (lower mini mental state examination, P = 0.025, and slower Trail Making Test A, P = 0.034).

Conclusions

Coronary microcirculatory dysfunction is frequent in patients with CAD and correlates with CSVD, abnormal cerebral flow haemodynamics, and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and the brain are part of a single pathological process affecting microcirculation in patients with CAD.

Clinical Trial Registration

ClinicalTrials.gov NCT04131075.
Cardiac troponin release following coronary artery bypass grafting: mechanisms and clinical implications
Authors: Heuts Samuel , Gollmann-Tepeköylü Can , Denessen Ellen J S , Olsthoorn Jules R , Romeo Jamie L R , Maessen Jos G , van ‘t Hof Arnoud W J , Bekers Otto , Hammarsten Ola , Pölzl Leo , Holfeld Johannes , Bonaros Nikolaos , van der Horst Iwan C C , Davidson Sean M , Thielmann Matthias , Mingels Alma M A
Published: November 2022

The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.
High-density lipoprotein revisited: biological functions and clinical relevance
Authors: von Eckardstein Arnold , Nordestgaard Børge G , Remaley Alan T , Catapano Alberico L
Published: November 2022

Previous interest in high-density lipoproteins (HDLs) focused on their possible protective role in atherosclerotic cardiovascular disease (ASCVD). Evidence from genetic studies and randomized trials, however, questioned that the inverse association of HDL-cholesterol (HDL-C) is causal. This review aims to provide an update on the role of HDL in health and disease, also beyond ASCVD. Through evolution from invertebrates, HDLs are the principal lipoproteins, while apolipoprotein B-containing lipoproteins first developed in vertebrates. HDLs transport cholesterol and other lipids between different cells like a reusable ferry, but serve many other functions including communication with cells and the inactivation of biohazards like bacterial lipopolysaccharides. These functions are exerted by entire HDL particles or distinct proteins or lipids carried by HDL rather than by its cholesterol cargo measured as HDL-C. Neither does HDL-C measurement reflect the efficiency of reverse cholesterol transport. Recent studies indicate that functional measures of HDL, notably cholesterol efflux capacity, numbers of HDL particles, or distinct HDL proteins are better predictors of ASCVD events than HDL-C. Low HDL-C levels are related observationally, but also genetically, to increased risks of infectious diseases, death during sepsis, diabetes mellitus, and chronic kidney disease. Additional, but only observational, data indicate associations of low HDL-C with various autoimmune diseases, and cancers, as well as all-cause mortality. Conversely, extremely high HDL-C levels are associated with an increased risk of age-related macular degeneration (also genetically), infectious disease, and all-cause mortality. HDL encompasses dynamic multimolecular and multifunctional lipoproteins that likely emerged during evolution to serve several physiological roles and prevent or heal pathologies beyond ASCVD. For any clinical exploitation of HDL, the indirect marker HDL-C must be replaced by direct biomarkers reflecting the causal role of HDL in the respective disease.
Prevalence, trends, and outcomes of cardiovascular diseases in pregnant patients in the USA: 2010–19
Authors: Majmundar Monil , Doshi Rajkumar , Patel Kunal N , Zala Harshvardhan , Kumar Ashish , Kalra Ankur
Published: November 2022

Aims

Contemporary data on the prevalence, trends, and outcomes of cardiovascular diseases (CVDs) in pregnant patients are limited. This study aimed to analyse the prevalence, trends, and outcomes of CVD and their subtypes in hospitalized pregnant patients in the USA.

Methods and results

This retrospective population-based cohort study used the Nationwide Readmission Database to identify all hospitalized pregnant patients from 1 January 2010, to 31 December 2019. Data analyses were conducted from January to February 2022. Pregnancy-associated hospitalizations were identified. The main outcomes were the prevalence and trend of CVD in pregnant patients. 39 212 104 hospitalized pregnant patients were identified: 4 409 924 with CVD (11.3%) and 34 802 180 without CVD (88.8%). The annual age-adjusted CVD prevalence increased from 9.2% in 2010 to 14.8% in 2019 (P < 0.001). Hypertensive disorder of pregnancy (1069/10 000) was the most common, and aortic dissection (0.1/10 000) was the least common CVD. The trends of all CVD subtypes increased; however, the trend of valvular heart disease decreased. Age-adjusted in-hospital all-cause mortality was 8.2/10 000 in CVD, but its trend decreased from 8.1/10 000 in 2010 to 6.5/10 000 in 2019 (P < 0.001). CVD was associated with 15.51 times higher odds of in-hospital all-cause mortality compared with non-CVD patients [odds ratio (OR): 15.51, 95% confidence interval (CI)13.22–18.20, P < 0.001]. CVD was associated with higher 6-week postpartum readmission (OR: 1.97, 95% CI: 1.95–1.99), myocardial infarction (OR: 3.04, 95% CI: 2.57–3.59), and stroke (OR: 2.66, 95% CI: 2.41–2.94)(P < 0.001 for all).

Conclusion

There is an increasing age-adjusted trend in overall CVD and its subtypes among pregnant patients in the USA from 2010 to 2019. Pregnant patients with CVD had higher odds of in-hospital mortality than those without CVD. However, in-hospital all-cause mortality among patients with and without CVD has decreased over the past 10 years. CVD was associated with higher 6-week postpartum all-cause readmission, myocardial infarction, and stroke rates.
Surgical or percutaneous coronary revascularization for heart failure: an in silico model using routinely collected health data to emulate a clinical trial
Authors: Pathak Suraj , Lai Florence Y , Miksza Joanne , Petrie Mark C , Roman Marius , Murray Sarah , Dearling Jeremy , Perera Divaka , Murphy Gavin J
Published: November 2022

Aims

The choice of revascularization with coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence.

Methods and results

A trial of CABG vs. PCI in people with heart failure (HF) was modelled in silico using routinely collected healthcare data. The in silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Allocation to CABG vs. complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95% confidence intervals (CIs). The target population included 13 519 HF patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1% in the CABG group and 70.0% in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE −16.2%, 95% CI −20.6% to −11.8%), with comparable estimates in the unmatched target population (ATE −15.5%, 95% CI −17.5% to −13.5%).

Conclusion

In people with HF, in silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years vs. complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.
Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program
Authors: Lichtenstein Gary R , Bressler Brian , Francisconi Carlos , Vermeire Severine , Lawendy Nervin , Salese Leonardo , Sawyerr Gosford , Shi Hongjiong , Su Chinyu , Judd Donna T , Jones Thomas , Loftus Edward V
Published: November 2022

Background

In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program.

Methods

Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received ≥ 1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis.

Results

In the Overall Cohort (1157 patients with ≤ 6.8 years’ tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups.

Conclusions

Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy.

ClinicalTrials.gov Registration Numbers

NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.
Childhood socio-economic circumstances and dementia: prospective register-based cohort study of adulthood socio-economic and cardiovascular health mediators
Authors: Korhonen Kaarina , Leinonen Taina , Tarkiainen Lasse , Einiö Elina , Martikainen Pekka
Published: November 2022

Background

This study analysed the association between childhood socio-economic circumstances and the risk of dementia, and investigated the mediating role of potentially modifiable risk factors including adulthood socio-economic position and cardiovascular health.

Methods

We used a 10% sample of the 1950 Finnish population census linked with subsequent population and health registers (n = 95 381). Information of socio-economic characteristics, family structure and housing conditions at the age of 0–15 years was obtained from the 1950 census. We identified cohort members who developed dementia in 2000–2018 using national hospital, medication and death registers. Discrete time survival analysis using logistic regression and mediation analysis applying the Karlson–Holm–Breen (KHB) method were employed.

Results

An excess risk of dementia was observed for household crowding [odds ratio (OR) = 1.10; 95% CI 1.02–1.18 for 3 to <4 persons per heated room; OR = 1.19; 95% CI 1.11–1.27 for ≥4 persons], single-father family (OR = 1.27; 95% CI 1.07–1.51) and eastern and northern region of residence (OR = 1.19; 95% CI 1.10–1.28). The effects of single-father family and region of residence were mostly direct with adulthood characteristics mediating 14% and 29% of the total effect, respectively. The largest indirect effect was observed for household crowding mediated through adulthood socio-economic position (47–65%).

Conclusions

The study shows that childhood socio-economic circumstances are associated with dementia, and that the underlying mechanisms only partly relate to adulthood socio-economic position and cardiovascular health. Socio-economic and health interventions targeted at families with children may carry long-term benefits by contributing to a lower dementia risk in later life.
Antecedents and consequences of Americans’ COVID-19 conspiracy beliefs: a focus on support for trump, populism, institutional trust, media consumption, and mask-wearing attitudes
Authors: Lee Taeyoung , Santillana Melissa , Lacasa-Mas Ivan , Ashe Ivy
Published: November 2022

During the COVID-19 pandemic, there have been growing concerns about conspiracy theories across the globe. Especially in the United States, conspiratorial narratives have been promoted by political figures and moved to public discourse from the fringe, shaping public opinion and hampering preventive measures. This study examines a host of political and communicative factors that might contribute to Americans’ belief in COVID-19 conspiracy theories and how such belief is associated with attitudes toward mask-wearing. Findings from a U.S. national two-wave panel survey showed that support for Donald Trump was the strongest predictor of conspiracy beliefs. Populism, trust in scientific institutions, conservative media use, and social media use predicted such beliefs as well. We also found a negative relationship between conspiracy beliefs and mask-wearing attitudes, suggesting that conspiracy beliefs might threaten public health by hindering preventive behavior. The implications of these findings are discussed.
Linking sleep, political ideology, and religious observance: a multi-national comparison
Authors: Ksiazkiewicz Aleksander , Erol Fatih
Published: November 2022

Sleep is fundamental to life and essential to one’s health behavior, scholastic achievement, and work performance. Recent years have seen an increase in empirical investigations incorporating sleep research into political science. This study complements existing sleep-politics studies by examining the associations between chronotype (a person’s preferred time to sleep and wake up) and attitudinal and behavioral political outcomes (left–right ideology and social conservatism proxied by religious service attendance). We analyze representative samples from 10 national contexts (Finland, Greece, Ireland, Mexico, the Netherlands, New Zealand, the Philippines, Russia, South Korea, and Switzerland) to test our hypotheses. The results demonstrate that morning chronotype has significant links with political conservatism in six national contexts depending on model specification (most robustly in Switzerland). Unexpectedly, the morning chronotype may have links to liberalism in three other countries depending on model specification (most robustly in Russia). The results for religious observance are more uniform, indicating a link between morningness and greater religious observance across all cases in many specifications (excepting a reversed relationship in New Zealand in some models). Urbanization, seasonal effects, geographical characteristics, and religious denominations are explored as potential confounders.
Invariance of Plurigenera Fails in Positive and Mixed Characteristic
Authors: Brivio Iacopo
Published: November 2022

We construct families of elliptic surface pairs with terminal singularities over a DVR of positive or mixed characteristic $(X,B)\to {\operatorname {Spec}} R$, such that $P_m(X_k,B_k)>P_m(X_K,B_K)$ for all sufficiently divisible $m>0$. In particular, this shows that invariance of all sufficiently divisible plurigenera does not follow from the MMP and abundance conjectures.
On Citing Dobzhansky about the Significance of Evolution to Biology
Authors: Giaimo Stefano
Published: November 2022

Synopsis

Evolutionary thinking illuminates biology. Dobzhansky advocated this view in two distinct papers. The earliest paper (1964) is a discussion of the relationship between distinct biological disciplines, and one of the key ideas is that evolution is an integrative principle of biology. The later paper (1973) is a long argument to the effect that evolution makes more sense of the living than some creationist doctrines. The first paper should then be the primary reference for those biologists who cite Dobzhansky to champion among their peers the added value of evolutionary thinking in a specific scientific problem. Here, looking at citation data, we find evidence that this expected referencing practice does not coincide with the actual referencing practice in the scientific literature.
Repeated Alpine Flight Loss Within the Widespread New Zealand StoneflyNesoperla fulvescensHare (Plecoptera: Gripopterygidae)
Authors: McCulloch Graham A , Foster Brodie J , Dutoit Ludovic , Waters Jonathan M
Published: November 2022

Flight loss is a common feature of upland insect assemblages, with recent studies detecting parallel wing reduction events across independent alpine lineages. However, the geographic scale over which such repeated evolution can operate remains unclear. In this study, we use genotyping-by-sequencing to assess the genomic relationships among vestigial-winged and full-winged populations of the widespread New Zealand stonefly Nesoperla fulvescens, to test for repeated wing loss events over small spatial scales. Biogeographic analyses indicate that alpine wing loss in this widespread species is restricted to a single, narrow mountain range. Intriguingly, our coalescent analyses indicate that upland vestigial-winged N. fulvescens populations are not sister to one another, suggesting wings have been lost independently in disjunct populations of this species, over a <30 km scale. Our results suggest that selection against flight above the alpine treeline can drive rapid and repeated adaptation even across narrow spatial scales. We propose that such repetitive processes may represent a far more pervasive feature of alpine insect adaptation than is currently recognized.
Using similar patients to predict complication in patients with diabetes, hypertension, and lipid disorder: a domain knowledge-infused convolutional neural network approach
Authors: Oei Ronald Wihal , Hsu Wynne , Lee Mong Li , Tan Ngiap Chuan
Published: November 2022

Objective

This study aims to develop a convolutional neural network-based learning framework called domain knowledge-infused convolutional neural network (DK-CNN) for retrieving clinically similar patient and to personalize the prediction of macrovascular complication using the retrieved patients.

Materials and Methods

We use the electronic health records of 169 434 patients with diabetes, hypertension, and/or lipid disorder. Patients are partitioned into 7 subcohorts based on their comorbidities. DK-CNN integrates both domain knowledge and disease trajectory of patients over multiple visits to retrieve similar patients. We use normalized discounted cumulative gain (nDCG) and macrovascular complication prediction performance to evaluate the effectiveness of DK-CNN compared to state-of-the-art models. Ablation studies are conducted to compare DK-CNN with reduced models that do not use domain knowledge as well as models that do not consider short-term, medium-term, and long-term trajectory over multiple visits.

Results

Key findings from this study are: (1) DK-CNN is able to retrieve clinically similar patients and achieves the highest nDCG values in all 7 subcohorts; (2) DK-CNN outperforms other state-of-the-art approaches in terms of complication prediction performance in all 7 subcohorts; and (3) the ablation studies show that the full model achieves the highest nDCG compared with other 2 reduced models.

Discussion and Conclusions

DK-CNN is a deep learning-based approach which incorporates domain knowledge and patient trajectory data to retrieve clinically similar patients. It can be used to assist physicians who may refer to the outcomes and past treatments of similar patients as a guide for choosing an effective treatment for patients.
Mis-mappings between a producer’s quantitative test codes and LOINC codes and an algorithm for correcting them
Authors: McDonald Clement J , Baik Seo H , Zheng Zhaonian , Amos Liz , Luan Xiaocheng , Marsolo Keith , Qualls Laura
Published: November 2022

Objectives

To access the accuracy of the Logical Observation Identifiers Names and Codes (LOINC) mapping to local laboratory test codes that is crucial to data integration across time and healthcare systems.

Materials and Methods

We used software tools and manual reviews to estimate the rate of LOINC mapping errors among 179 million mapped test results from 2 DataMarts in PCORnet. We separately reported unweighted and weighted mapping error rates, overall and by parts of the LOINC term.

Results

Of included 179 537 986 mapped results for 3029 quantitative tests, 95.4% were mapped correctly implying an 4.6% mapping error rate. Error rates were less than 5% for the more common tests with at least 100 000 mapped test results. Mapping errors varied across different LOINC classes. Error rates in chemistry and hematology classes, which together accounted for 92.0% of the mapped test results, were 0.4% and 7.5%, respectively. About 50% of mapping errors were due to errors in the property part of the LOINC name.

Discussions

Mapping errors could be detected automatically through inconsistencies in (1) qualifiers of the analyte, (2) specimen type, (3) property, and (4) method. Among quantitative test results, which are the large majority of reported tests, application of automatic error detection and correction algorithm could reduce the mapping errors further.

Conclusions

Overall, the mapping error rate within the PCORnet data was 4.6%. This is nontrivial but less than other published error rates of 20%–40%. Such error rate decreased substantially to 0.1% after the application of automatic detection and correction algorithm.
Disparity in checkpoint inhibitor utilization among commercially insured adult patients with metastatic lung cancer
Authors: Li Meng , Liao Kaiping , Chen Alice J , Cascone Tina , Shen Yu , Lu Qian , Shih Ya-Chen Tina
Published: November 2022

Background

There is a lack of evidence from nationwide samples on the disparity of initiating immune checkpoint inhibitors (ICIs) after metastatic lung cancer diagnosis.

Methods

We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large, nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. Independent variables included county-level measures (quintiles of percentage of racialized population, quintiles of percentage of population below poverty, urbanity, and density of medical oncologists) and patient characteristics (age, sex, Charlson comorbidity index, Medicare Advantage, and year of diagnosis). All tests were 2-sided.

Results

A total of 17 022 patients were included. Counties with a larger proportion of racialized population appeared to be more urban, have a greater percentage of its residents in poverty, and have a higher density of medical oncologists. In Cox analysis, the adjusted hazard ratio of the second, third, fourth, and highest quintile of percentage of racialized population were 0.89 (95% confidence interval [CI] = 0.82 to 0.98), 0.85 (95% CI = 0.78 to 0.93), 0.78 (95% CI = 0.71 to 0.86), and 0.71 (95% CI = 0.62 to 0.81), respectively, compared with counties in the lowest quintile. The slower ICI therapy initiation was driven by counties with the highest percentage of Hispanic population and other non-Black racialized groups.

Conclusions

Commercially insured patients with metastatic lung cancer who lived in counties with greater percentage of racialized population had slower initiation of ICI therapy after lung cancer diagnosis, despite greater density of oncologists in their neighborhood.
Comparison of Mental Health Visits at a Military Treatment Facility Emergency Department Pre- and Post-COVID-19 Pandemic
Authors: Wojahn Amanda , Reilly Erin , Morrison Theodore C , Lemieux Renée S , Grimaldo Felipe
Published: November 2022

Introduction

There is a paucity of quantitative research regarding the effect of coronavirus 2019 (COVID-19) on Emergency Department (ED) visits in the United States, and specifically mental health–related ED visits. The small existing body of research describes an overall decline in ED visits worldwide; however, there are anecdotal reports that psychiatric complaints to the ED have increased during the pandemic. The primary objective of this study was to describe the volume of mental health ED visits at a single ED during the COVID-19 pandemic compared to previous years.

Materials and Methods

This was a single-center, retrospective chart review of adult patients evaluated in the ED at an academic military medical facility from March to December of 2017-2020 for mental health. The electronic medical record was queried for mental health International Classification of Diseases, 10th Revision diagnosis codes. Demographic data including age, gender, disposition, diagnosis, and beneficiary status were collected, and Pearson Chi-Square was used to assess for statistical significance between years.

Results

There was a total of 1,486 mental health ED visits from March to December 2020, compared to an average of 1,668 visits from March to December 2017-2019. Statistically significant (P < 0.05) differences, between 2020 and the prior 3 years combined, were identified in the categories of age, disposition, beneficiary status, and diagnosis. In 2020, there was a lower proportion of visits for patients aged ≥60 (1.2%) than in 2017-2019 (2.5%). Active-duty patients comprised a higher proportion of mental health visits in 2020 (82.4%) versus 2017-2019 (77%). Proportionately fewer patients were admitted in 2020 (25.2%) versus 2017-2019 (29.2%). Adjustment disorders made up 19.0% of visits in 2020 versus 23.2% in 2017-2019, and suicidal ideation and intentional self-inflicted injury comprised 43.3% in 2020 compared with 40.4% in 2017-2019.

Conclusion

There was a significant decline in ED visits for patients over the age of 60 but a significant increase in visits for active-duty patients. Fewer patients were admitted compared to previous years. There was a significant increase in patients diagnosed with suicidal ideation and intentional self-inflicted injury in 2020 compared to previous years. Alarmingly, this study shows increased rates of self-harm and suicidal ideation. Further study is needed to determine why these effects were seen and if there is a higher risk for suicide attempt or completion in these populations. These results indicate that military leadership and the military health system is failing to adequately support and protect service members and their families during these uniquely stressful times. High-level attention to this issue by military leadership is required; the readiness and safety of the nation’s fighting force is at stake.
Modification of the radioactive heat budget of Earth-like exoplanets by the loss of primordial atmospheres
Authors: Erkaev N V , Scherf M , Herbort O , Lammer H , Odert P , Kubyshkina D , Leitzinger M , Woitke P , O’Neill C
Published: November 2022

The initial abundance of radioactive heat producing isotopes in the interior of terrestrial planets are important drivers of its thermal evolution and the related tectonics and possible evolution to an Earth-like habitat. The moderately volatile element K can be outgassed from a magma ocean into H2-dominated primordial atmospheres of protoplanets with assumed masses between 0.55 and 1.0MEarth at the time when the gas disc evaporated. We estimate this outgassing and let these planets grow through impacts of depleted and non-depleted material that resembles the same 40K abundance of average carbonaceous chondrites until the growing protoplanets reach 1.0MEarth. We examine different atmospheric compositions and, as a function of pressure and temperature, calculate the proportion of K by Gibbs Free Energy minimization using the ggchem code. We find that for H2-envelopes and for magma ocean surface temperatures that are ≥ 2500 K, no K condensates are thermally stable, so that outgassed 40K can populate the atmosphere to a great extent. However, due to magma ocean turnover time and the limited diffusion of 40K into the upper atmosphere, from the entire 40K in the magma ocean only a fraction may be available for escaping into space. The escape rates of the primordial atmospheres and the dragged 40K are simulated for different stellar EUV activities with a multispecies hydrodynamic upper atmosphere evolution model. Our results show that one can expect that different initial abundances of heat producing elements will result in different thermal and tectonic histories of terrestrial planets and their habitability conditions.