bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of hemoglobin A1c time in range with risk for diabetes complications
Authors: Mohr David C , Zhang Libin , Prentice Julia C , Nelson Richard E , Li Donglin , Pleasants Erin , Conlin Paul R 
Published: July 2022

IntroductionWe assessed the association between hemoglobin A1c time in range (A1c TIR), based on unique patient-level A1c target ranges, with risks of developing microvascular and macrovascular complications in older adults with diabetes.Research design and methodsWe used a retrospective observational study design and identified patients with diabetes from the Department of Veterans Affairs (n=397 634). Patients were 65 years and older and enrolled in Medicare during the period 2004–2016. Patients were assigned to individualized A1c target ranges based on estimated life expectancy and the presence or absence of diabetes complications. We computed A1c TIR for patients with at least four A1c tests during a 3-year baseline period. The association between A1c TIR and time to incident microvascular and macrovascular complications was studied in models that included A1c mean and A1c SD.ResultsWe identified 74 016 patients to assess for incident microvascular complications and 89 625 patients to assess for macrovascular complications during an average follow-up of 5.5 years. Cox proportional hazards models showed lower A1c TIR was associated with higher risk of microvascular (A1c TIR 0% to <20%; HR=1.04; 95%) and macrovascular complications (A1c TIR 0% to <20%; HR=1.07; 95%). A1c mean was associated with increased risk of microvascular and macrovascular complications but A1c SD was not. The association of A1c TIR with incidence and progression of individual diabetes complications within the microvascular and macrovascular composites showed similar trends.ConclusionsMaintaining stability of A1c levels in unique target ranges was associated with lower likelihood of developing microvascular and macrovascular complications in older adults with diabetes.
Guillain-Barré syndrome following SARS-CoV-2 vaccination in the UK: a prospective surveillance study
Authors: Tamborska Arina A , Singh Bhagteshwar , Leonhard Sonja E , Hodel Eva Maria , Stowe Julia , Watson-Fargie Taylor , Fernandes Peter M , Themistocleous Andreas C , Roelofs Jacob , Brennan Kathryn , Morrice Caroline , Michael Benedict D , Jacobs Bart C , McDonald Helen , Solomon Tom 
Published: July 2022

ObjectiveTo investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.MethodsWe captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).ResultsBetween 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study.InterpretationMost reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.
The acute effect of maximal exercise on arterial stiffness in adults with and without intellectual and developmental disabilities
Authors: Melo Xavier , Marôco João Luís , Pinto Rita , Angarten Vitor , Coimbra Manuel , Correia Duarte , Roque Mafalda , Reis Joana , Santos Vanessa , Fernhall Bo , Santa-Clara Helena 
Published: July 2022

We compared central and peripheral arterial stiffness response patterns between persons with and without intellectual and developmental disabilities (IDD) of different age groups at rest and following a cardiopulmonary exercise test (CPET). Fifteen young adults with and without IDD, and 15 middle-aged adults without IDD performed a CPET. Central and peripheral arterial stiffness were measured at rest and following CPET using estimates of carotid-femoral (cfPWV), carotid-radial (crPWV), and carotid-ankle (cdPWV) pulse wave velocity derived from piezoelectric mechano-transducers. cfPWV remained unchanged following CPET in adults with and without IDD but increased in middle-aged adults ( d = 0.85; 95% CI: 0.27–1.42 m·s–1, p = 0.005), whereas cdPWV was similarly reduced ( d = –0.77; 95% CI: –1.06 to –0.48 m·s–1, p < 0.001) in all groups. crPWV remained unchanged in all groups. These results were independent of exercise-related changes in mean arterial pressure. Overall group differences suggested that persons with IDD ( d = –1.78; 95% CI: –3.20 to –0.37 m·s–1, p = 0.009) and without IDD ( d = –1.84; 95% CI: –3.26 to –0.43 m·s–1, p = 0.007) had lower cfPWV than middle-aged adults. We found no evidence of early vascular aging and diminished vascular reserve following CPET in adults with IDD.
Enemy release from beech bark disease coincides with upslope shift of American beech
Authors: Cleavitt Natalie L. , Montague Madeline S. , Battles John J. , Box Olivia F. , Matthes Jaclyn Hatala , Fahey Timothy J. 
Published: July 2022

Upslope shifts in plant distributions are often attributed to warming climate and lengthening of the growing season; however, biotic interactions may also contribute. The impacts of pests and pathogens are often sensitive to climate change and can vary along the climatic gradient associated with elevation. American beech ( Fagus grandifolia) has moved upslope throughout the northeastern United States. Meanwhile, beech growth and longevity have decreased as a result of beech bark disease (BBD), a decline disease caused by the introduced European felted beech scale insect ( Cryptococcus fagisuga) and native fungi from the genus Neonectria. Within a forested landscape spanning 250–1150 m elevation, we examined the relationships between elevation, beech demography and BBD to explore whether release from BBD at higher elevation may contribute to the upslope expansion of beech. Beech has shifted upslope at a rate of 1 m⋅year−1coincident with lower mortality, higher recruitment, faster growth, lower BBD severity, and higher sapling densities at higher elevations. We suggest that climatic constraints on the beech scale insect at high elevations has led to a lower impact of BBD, which contributed to higher rates of beech growth, survival, and recruitment and in turn facilitated the regional upslope shift of beech.
Opioid receptor μ, not δ and κ, modulate food intake induced by ghrelin in laying chickens
Authors: Baghaeikia Shilan , Fallah Hamed , Khodadadi Mina , Yousefvand Shiba , Mahdavi Kimia , Zendehdel Morteza , Rahmani Behrouz 
Published: July 2022

Evidence from animal studies suggests that the opioidergic system and ghrelin have a regulatory role in food intake, but their interaction(s) have not been studied in laying chickens. So in this study, four experiments (each included four groups) were designed. The first experiment was performed to evaluate the effect of ghrelin on the cumulative food intake. Experiments 2–4 were designed to investigate the possibility of μ, δ, or κ opioid receptors mediating ghrelin-induced hypophagia. All drugs were injected intracerebroventricularly (ICV) at 5 days of age. The results of this study showed that the ICV injection of 1.5 nmol ghrelin did not affect cumulative food intake. However, ICV injection of ghrelin with doses of 3 and 6 nmol significantly reduced the cumulative food intake ( p < 0.05). However, co-injection of ghrelin with naltrindole and norbinaltorphimine did not show a significant change in decreased food intake compared with ghrelin. Also, opioid μ receptor gene expression significantly increased ( p < 0.05), but δ and κ opioid receptors’ gene expression did not significantly change. These results indicated that the opioidergic system is involved in developing ghrelin-induced hypophagic effects in laying chickens. Accordingly, this effect of ghrelin to modify the nutritional behavior is possibly mediated by opioid μ receptor.
Design of an enhanced mechanism for a new Kibble balance directly traceable to the quantum SI
Authors: Keck Lorenz , Seifert Frank , Newell David , Schlamminger Stephan , Theska René , Haddad Darine 
Published: July 2022

AbstractThe “Quantum Electro-Mechanical Metrology Suite” (QEMMS) is being designed and built at the National Institute of Standards and Technology. It includes a Kibble balance, a graphene quantum Hall resistance array and a Josephson voltage system, so that it is a new primary standard for the unit of mass, the kilogram, directly traceable to the International System of Units (SI) based on quantum constants. We are targeting a measurement range of 10 g to 200 g and optimize the design for a relative combined uncertainty of $2\times 10^{-8}$
2
×

10

−
8

for masses of 100 g. QEMMS will be developed as an open hardware and software design. In this article, we focus on the design of an enhanced moving and weighing mechanism for the QEMMS based on flexure pivots.
Intratumoral Heterogeneity and Immune Modulation in Lung Adenocarcinoma in Female Smokers and Never Smokers
Authors: Trefzer Timo B. , Schneider Marc A. , Jechow Katharina , Chua Robert Lorenz , Muley Thomas , Winter Hauke , Kriegsmann Mark , Meister Michael , Eils Roland , Conrad Christian 
Published: July 2022

Abstract
Lung cancer remains the leading cause of cancer-related death worldwide, despite declining smoking prevalence in industrialized countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who have never smoked, with an observable bias toward female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumor evolution and progression in never smokers is therefore highly needed. Here, we used single-nucleus transcriptomics of surgical lung adenocarcinoma (LUAD) and normal lung tissue samples from patients with or without a history of smoking. Immune cells as well as fibroblasts and endothelial cells responded to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In LUAD, characterization of differentially expressed transcriptional programs in macrophages and cancer-associated fibroblasts provided insight into how the niche favors tumor progression. Within tumors, eight subpopulations of neoplastic cells were identified in female smokers and never smokers. Pseudotemporal ordering inferred a trajectory toward two differentiated tumor cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumor growth exhibited differential immune modulating signatures in both patient groups. Collectively, these results resolve cellular heterogeneity and immune interactions in LUAD, with a special emphasis on female never smokers.

Significance:
Single-cell analysis of healthy lung tissue and lung cancer reveals distinct tumor cell populations, including cells with differential immune modulating capacity between smokers and never smokers, which could guide future therapeutic strategies.
Human-Induced Pluripotent Stem Cell–Derived Cardiomyocyte Model for
TNNT2
Δ160E-Induced Cardiomyopathy
Authors: Kondo Takumi , Higo Shuichiro , Shiba Mikio , Kohama Yasuaki , Kameda Satoshi , Tabata Tomoka , Inoue Hiroyuki , Okuno Shota , Ogawa Shou , Nakamura Satoki , Takeda Maki , Ito Emiko , Li Junjun , Liu Li , Kuramoto Yuki , Lee Jong-Kook , Takashima Seiji , Miyagawa Shigeru , Sawa Yoshiki , Hikoso Shungo , Sakata Yasushi 
Published: July 2022

Background:

The Δ160E mutation in
TNNT2
, which encodes troponin T, is a rare pathogenic variant identified in patients with hypertrophic cardiomyopathy and is associated with poor prognosis. Thus, a convenient human model recapitulating the pathological phenotype caused by
TNNT2
Δ160E is required for therapeutic development.

Methods:

We identified a heterozygous in-frame deletion mutation (c.478_480del, p.Δ160E) in
TNNT2
in a patient with familial hypertrophic cardiomyopathy showing progressive left ventricular systolic dysfunction, leading to advanced heart failure. To investigate the pathological phenotype caused by Δ160E, we generated a set of isogenic induced pluripotent stem cells carrying the heterozygous Δ160E, homozygously corrected or homozygously introduced Δ160E using genome editing and differentiated them into cardiomyocytes (Hetero-Δ160E-, wild type-, and Homo-Δ160E-induced pluripotent stem cells [iPSC]-derived cardiomyocytes [iPSC-CMs]).

Results:
Hetero-Δ160E-iPSC-CMs exhibited prolonged calcium decay, relaxation impairment, and hypertrophy compared to wild type-iPSC-CMs. Notably, these phenotypes were further exacerbated in Homo-Δ160E-iPSC-CMs. Overexpression of R-GECO-fused Δ160E mutant troponin T prolonged decay time and time to peak of the myofilament-localized calcium transient in iPSC-CMs, indicating that sarcomeric calcium retention with Δ160E may affect intracellular calcium concentration. High-content imaging analysis detected remarkable nuclear translocation of NFATc1, especially in Homo-Δ160E-iPSC-CMs, indicating that the Δ160E mutation promotes hypertrophic signaling pathway in a dose-dependent manner. Increased phosphorylation of CaMKIIδ (calcium/calmodulin-dependent protein kinase IIδ) and phospholamban at Thr17 was observed in Homo- and Hetero-Δ160E-iPSC-CMs. Epigallocatechin-3-gallate, a calcium desensitizing compound, shortened prolonged calcium decay and relaxation duration in Δ160E-iPSC-CMs.

Conclusions:

Isogenic iPSC-CMs recapitulate the prolonged calcium decay, relaxation impairment, and subsequent calcium-regulated signaling pathways caused by the
TNNT2
Δ160E mutation and can serve as a human model for therapeutic development to prevent hypertrophic cardiomyopathy pathology.
DC ENaC-Dependent Inflammasome Activation Contributes to Salt-Sensitive Hypertension
Authors: Pitzer Ashley , Elijovich Fernando , Laffer Cheryl L. , Ertuglu Lale A. , Sahinoz Melis , Saleem Mohammad , Krishnan Jaya , Dola Thanvi , Aden Luul A. , Sheng Quanhu , Raddatz Michael A. , Wanjalla Celestine , Pakala Suman , Davies Sean S. , Patrick David M. , Kon Valentina , Ikizler T. Alp , Kleyman Thomas , Kirabo Annet 
Published: July 2022

Background:
Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. In the current study, we hypothesized that ENaC-dependent entry of sodium into APCs activates the NLRP3 (NOD [nucleotide-binding and oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome via IsoLG formation leading to salt-sensitive hypertension.

Methods:
We performed RNA sequencing on human monocytes treated with elevated sodium in vitro and Cellular Indexing of Transcriptomes and Epitopes by Sequencing analysis of peripheral blood mononuclear cells from participants rigorously phenotyped for salt sensitivity of blood pressure using an established inpatient protocol. To determine mechanisms, we analyzed inflammasome activation in mouse models of deoxycorticosterone acetate salt–induced hypertension as well as salt-sensitive mice with ENaC inhibition or expression, IsoLG scavenging, and adoptive transfer of wild-type dendritic cells into NLRP3 deficient mice.

Results:
We found that high levels of salt exposure upregulates the NLRP3 inflammasome, pyroptotic and apoptotic caspases, and IL (interleukin)-1β transcription in human monocytes. Cellular Indexing of Transcriptomes and Epitopes by Sequencing revealed that components of the NLRP3 inflammasome and activation marker IL-1β dynamically vary with changes in salt loading/depletion. Mechanistically, we found that sodium-induced activation of the NLRP3 inflammasome is ENaC and IsoLG dependent. NLRP3 deficient mice develop a blunted hypertensive response to elevated sodium, and this is restored by the adoptive transfer of NLRP3 replete APCs.

Conclusions:
These findings reveal a mechanistic link between ENaC, inflammation, and salt-sensitive hypertension involving NLRP3 inflammasome activation in APCs. APC activation via the NLRP3 inflammasome can serve as a potential diagnostic biomarker for salt sensitivity of blood pressure.
Stability and dynamics of a spectral graph model of brain oscillations
Authors: Verma Parul , Nagarajan Srikantan , Raj Ashish 
Published: July 2022

Abstract
We explore the stability and dynamic properties of a hierarchical, linearized, and analytic spectral graph model for neural oscillations that integrates the structural wiring of the brain. Previously, we have shown that this model can accurately capture the frequency spectra and the spatial patterns of the alpha and beta frequency bands obtained from magnetoencephalography recordings without regionally varying parameters. Here, we show that this macroscopic model based on long-range excitatory connections exhibits dynamic oscillations with a frequency in the alpha band even without any oscillations implemented at the mesoscopic level. We show that depending on the parameters, the model can exhibit combinations of damped oscillations, limit cycles, or unstable oscillations. We determined bounds on model parameters that ensure stability of the oscillations simulated by the model. Finally, we estimated time-varying model parameters to capture the temporal fluctuations in magnetoencephalography activity. We show that a dynamic spectral graph modeling framework with a parsimonious set of biophysically interpretable model parameters can thereby be employed to capture oscillatory fluctuations observed in electrophysiological data in various brain states and diseases.
Functional coordinates: Modeling interactions between brain regions as points in a function space
Authors: Poskanzer Craig , Anzellotti Stefano 
Published: July 2022

Abstract
Here, we propose a novel technique to investigate nonlinear interactions between brain regions that captures both the strength and type of the functional relationship. Inspired by the field of functional analysis, we propose that the relationship between activity in separate brain areas can be viewed as a point in function space, identified by coordinates along an infinite set of basis functions. Using Hermite polynomials as bases, we estimate a subset of these values that serve as “functional coordinates,” characterizing the interaction between BOLD activity across brain areas. We provide a proof of the convergence of the estimates in the limit, and we validate the method with simulations in which the ground truth is known, additionally showing that functional coordinates detect statistical dependence even when correlations (“functional connectivity”) approach zero. We then use functional coordinates to examine neural interactions with a chosen seed region: the fusiform face area (FFA). Using k-means clustering across each voxel’s functional coordinates, we illustrate that adding nonlinear basis functions allows for the discrimination of interregional interactions that are otherwise grouped together when using only linear dependence. Finally, we show that regions in V5 and medial occipital and temporal lobes exhibit significant nonlinear interactions with the FFA.
Islam Compliance, beyond Sharīʿah Compliance: Toward a Broader Socio-Economic Transformation
Authors: Farooq Mohammad Omar 
Published: July 2022

Abstract
With the emergence and growth of the Islamic finance industry, Muslims now have at their disposal comprehensive Sharīʿah-compliant financial services. However, the notion of Sharīʿah compliance has rarely been deconstructed; essentially, it constitutes a prohibition-driven enterprise. While avoidance of the forbidden (ḥarām) is fundamentally important, Islam encompasses a great deal more than the impermissible. Approaching relevant issues from the perspective of Sharīʿah compliance, where legal aspects are overemphasized, leads to legalism where the principles, norms and values based on the Qurʾān and Sunnah are largely ignored or compromised. Limiting itself to merely avoiding the ḥarām has significantly handicapped the industry from identifying and endeavouring to address synergistically the broader socio-economic challenges. In this article, a modified conceptualization based on a more nuanced framework of ‘Islam-compliance’ is proposed and explored, especially from the perspective of value-orientation in Islam. The notion and framework of Islam compliance has broader implications beyond Islamic finance.
Institutionalized Riot Networks in India and Mobile Instant Messaging Platforms
Authors: Nizaruddin Fathima 
Published: July 2022

Abstract
The article uses the context of the Northeast Delhi riots in 2020 to examine how mobile instant messaging platforms have changed the nature of riot networks in India. What role does the state’s partisan approach play in aiding the use of these platforms by the constituents of such networks? Does the lack of adequate mechanisms to hold technology companies accountable contribute to how their platforms are used to aid the circulation of extreme speech, misinformation, and violence? The article explores these questions and argues for a framework to govern mobile instant messaging platforms that goes beyond attempts at self-regulation as well as efforts by national governments to regulate them. The complications that arise when such platforms are used by networks that favour majoritarian rulers are analyzed to examine the need for placing issues related to the governance of platform ecosystems within the framework of the protection of human rights.