bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Type 2 Diabetes: Implications from Large-Scale Studies
Authors: DeForest Natalie , Majithia Amit R. 
Published: March 2022

AbstractPurpose of ReviewType 2 diabetes (T2D) is a multifactorial, heritable syndrome characterized by dysregulated glucose homeostasis that results from impaired insulin secretion and insulin resistance. Genetic association studies have successfully identified hundreds of T2D risk loci implicating many genes in disease pathogenesis. In this review, we provide an overview of the recent T2D genetic studies from the past 3 years with particular focus on the effects of sample size and ancestral diversity on genetic discovery as well as discuss recent work on the use and limitations of genetic risk scores (GRS) for T2D risk prediction.Recent FindingsRecent large-scale, multi-ancestry genetic studies of T2D have identified over 500 novel risk loci. The genetic variants (i.e., single nucleotide polymorphisms (SNPs)) marking these novel loci in general have smaller effect sizes than previously discovered loci. Inclusion of samples from diverse ancestral backgrounds shows a few ancestry specific loci marked by common variants, but overall, the majority of loci discovered are common across ancestries. Inclusion of common variant GRS, even with hundreds of loci, does not substantially increase T2D risk prediction over standard clinical risk factors such as age and family history.SummaryCommon variant association studies of T2D have now identified over 700 T2D risk loci, half of which have been discovered in the past 3 years. These recent studies demonstrate that inclusion of ancestrally diverse samples can enhance locus discovery and improve accuracy of GRS for T2D risk prediction. GRS based on common variants, however, only minimally enhances risk prediction over standard clinical risk factors.
Options in the Treatment of Subacute Sclerosing Panencephalitis: Implications for Low Resource Areas
Authors: Samia Pauline , Oyieke Katherine , Tunje Dorcas , Udwadia-Hegde Anaita , Feemster Kristen , Oncel Ibrahim , Anlar Banu 
Published: March 2022

Abstract

Purpose of the review
Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, and frequently fatal neurodegenerative disorder caused by measles virus. The risk of SSPE remains significant globally, with fluctuating incidence noted in in tandem with measles vaccine uptake. This review aims to explore the current global status of SSPE, its treatment, and preventive measures.

Recent findings
An increase in measles cases have been reported in various parts of the world for different reasons related to the regional context of the outbreak. With reduction in measles vaccine doses since the onset of the COVID-19 pandemic, the future risk of SSPE can only accelerate. In recent years, subsequent cases of SSPE have been reported in the period following documented measles outbreaks in different settings. Concomitantly, there have been efforts to evaluate the efficacy of immunomodulatory, antiviral, and anti-seizure therapies that could ameliorate the devastating effects of this disease. This review elucidates on these approaches and their limitations, reasons for poor vaccine coverage in low- and middle-income countries, as well as the possible solutions to the prevention of measles and eventual avoidance of SSPE.

Summary
Prevention of measles virus infection with the resultant sequelae would be the most effective strategy for the management of SSPE. This approach would be particularly important in low resource setting that currently bears the double burden of widespread communicable diseases and malnutrition.
Cellular and Molecular Events Leading to Paraquat-Induced Apoptosis: Mechanistic Insights into Parkinson’s Disease Pathophysiology
Authors: See Wesley Zhi Chung , Naidu Rakesh , Tang Kim San 
Published: March 2022

Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal features of tremor, bradykinesia, rigidity, and postural instability, in addition to other non-motor symptoms. Pathologically, PD is attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta, with the hallmark of the presence of intracellular protein aggregates of α-synuclein in the form of Lewy bodies. The pathogenesis of PD is still yet to be fully elucidated due to the multifactorial nature of the disease. However, a myriad of studies has indicated several intracellular events in triggering apoptotic neuronal cell death in PD. These include oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, alteration in dopamine catabolism, inactivation of tyrosine hydroxylase, and decreased levels of neurotrophic factors. Laboratory studies using the herbicide paraquat in different in vitro and in vivo models have demonstrated the induction of many PD pathological features. The selective neurotoxicity induced by paraquat has brought a new dawn in our perspectives about the pathophysiology of PD. Epidemiological data have suggested an increased risk of developing PD in the human population exposed to paraquat for a long term. This model has opened new frontiers in the quest for new therapeutic targets for PD. The purpose of this review is to synthesize the relationship between the exposure of paraquat and the pathogenesis of PD in in vitro and in vivo models.
Comparison between PSM and IBESS approaches for the fatigue life estimation of weldments
Authors: Scacco Federico , Zerbst Uwe , Meneghetti Giovanni , Madia Mauro 
Published: March 2022

AbstractIn the framework of the fatigue assessment of welded components, several methods are available in design standards such as the nominal stress, hot-spot stress, notch stress and linear elastic fracture mechanics approaches. The present paper aims at comparing two advanced local approaches for the fatigue strength assessment of different welded joints made of steel. The first one is IBESS which is based on short crack fracture mechanics. The second one is the PSM which instead involves the strain energy density approach. Both methods will be briefly presented, and the fatigue life prediction results discussed. The results obtained for the joint geometries considered in this work show advantages and drawbacks of the approaches, which are thoroughly analysed as well.
Containing Hunger, Contesting Injustice? Exploring the Transnational Growth of Foodbanking- and Counter-responses- Before and During the COVID-19 Pandemic
Authors: Spring Charlotte , Garthwaite Kayleigh , Fisher Andy 
Published: March 2022

AbstractCOVID-19 caused levels of household food insecurity to spike, but the precarity of so many people in wealthy countries is an outgrowth of decades of eroding public provisions and labour protections that once protected people from hunger, setting the stage for the virus’ unevenly-distributed harms. The prominence of corporate-sponsored foodbanking as a containment response to pandemic-aggravated food insecurity follows decades of replacing rights with charity. We review structural drivers of charity’s growth to prominence as a hunger solution in North America, and of its spread to countries including the UK. By highlighting pre-pandemic pressures shaping foodbanking, including charities’ efforts to retool themselves as health providers, we ask whether anti-hunger efforts during the pandemic serve to contain ongoing socioeconomic crises and the unjust living conditions they cause, or contest them through transformative pathways to a just food system. We suggest that pandemic-driven philanthropic and state funding flows have bolstered foodbanking and the food system logics that support it. By contextualising the complex and variegated politics of foodbanking in broader movements, from community food security to food sovereignty, we reframe simplistic narratives of charity and highlight the need for justice-oriented structural changes in wealth redistribution and food system organisation if we are to prevent the kinds of emergency-within-emergency that we witnessed as COVID-19 revealed the proximity of many to hunger.
Daylight conditions in housing–Its role and priority in Danish building regulations
Authors: Mathiasen Nanet , Frandsen Anne Kathrine , Grønlund Louise 
Published: March 2022

AbstractIn a Danish context, the Building Regulation is the legislation for our built environment. Therefore, the focus of this survey is to investigate how Danish legislation treats questions on daylight in relation to the build environment. Furthermore, it looks at whether the specific ways of looking at daylight influence the general understanding of light and the processing of daylight design in the built environment. When acknowledging both its multifaceted character and the impact daylight has, as well as the inherent implications regulation can have on the practices that apply to them, the question remains as to how Danish building regulations treat questions of daylight in relation to the built environment. Furthermore, what is the implication of understanding these ways of looking at daylight? This survey is a profound study of 14 Danish building regulations, from the first historical regulations in 1856 up to the latest regulation of 2018. To investigate the role of daylight and its priority in Danish building regulations, daylight is defined through three theoretical topics: vision, energy, and health. This survey focuses on daylight in relation to private housing. Reviewing the 14 Danish Building Regulations illustrates how the understanding of daylight in relation to the built environment has changed. The different requirements on daylight design varies through time and reflects the political agenda of each specific historical period. This underlines how daylight is subject to changing agendas; however, it is rarely an agenda on its own.
A Clustering Method with Historical Data to Support Large-Scale Consensus-Reaching Process in Group Decision-Making
Authors: Xiong Kai , Dong Yucheng , Zhao Sihai 
Published: March 2022

AbstractWith the rapid development of information technology and social network, the large-scale group decision-making (LSGDM) has become more and more popular due to the fact that large numbers of stakeholders are involved in different decision problems. To support the large-scale consensus-reaching process (LCRP), this paper proposes a LCRP framework based on a clustering method with the historical preference data of all decision makers (DMs). There are three parts in the proposed framework: the clustering process, the consensus process and the selection process. In the clustering process, we make use of an extended k-means clustering technique to divide the DMs into several clusters based on their historical preferences data. Next, the consensus process consists of the consensus measure and the feedback adjustment. The consensus measure aims to calculate the consensus level among DMs based on the obtained clusters. If the consensus level fails to reach the pre-defined consensus threshold, it is necessary to make the feedback adjustment to modify DMs' preferences. At last, the selection process is carried out to obtain a collective ranking of all alternatives. An illustrative example and detailed simulation experiments are demonstrated to show the validity of the proposed framework against the traditional LCRP models which just consider the preference information of DMs at only one stage for clustering.
Heterogeneous Patterns of Aged Organic Carbon Export Driven by Hydrologic Flow Paths, Soil Texture, Fire, and Thaw in Discontinuous Permafrost Headwaters
Authors: Koch Joshua C. , Bogard Matthew J. , Butman David E. , Finlay Kerri , Ebel Brian , James Jason , Johnston Sarah Ellen , Jorgenson M. Torre , Pastick Neal J. , Spencer Robert G. M. , Striegl Robert , Walvoord Michelle , Wickland Kimberly P. 
Published: March 2022

AbstractClimate change is thawing and potentially mobilizing vast quantities of organic carbon (OC) previously stored for millennia in permafrost soils of northern circumpolar landscapes. Climate‐driven increases in fire and thermokarst may play a key role in OC mobilization by thawing permafrost and promoting transport of OC. Yet, the extent of OC mobilization and mechanisms controlling terrestrial‐aquatic transfer are unclear. We demonstrate that hydrologic transport of soil dissolved OC (DOC) from the active layer and thawing permafrost to headwater streams is extremely heterogeneous and regulated by the interactions of soils, seasonal thaw, fire, and thermokarst. Repeated sampling of streams in eight headwater catchments of interior Alaska showed that the mean age of DOC for each stream ranges widely from modern to ∼2,000 years B.P. Together, an endmember mixing model and nonlinear, generalized additive models demonstrated that Δ14C‐DOC signature (and mean age) increased from spring to fall, and was proportional to hydrologic contributions from a solute‐rich water source, related to presumed deeper flow paths found predominantly in silty catchments. This relationship was correlated with and mediated by catchment properties. Mean DOC ages were older in catchments with >50% burned area, indicating that fire is also an important explanatory variable. These observations underscore the high heterogeneity in aged C export and difficulty of extrapolating estimates of permafrost‐derived DOC export from watersheds to larger scales. Our results provide the foundation for developing a conceptual model of permafrost DOC export necessary for advancing understanding and prediction of land‐water C exchange in changing boreal landscapes.
Untangling the Solar Wind and Magnetospheric Drivers of the Radiation Belt Electrons
Authors: Wing Simon , Johnson Jay R. , Turner Drew L. , Ukhorskiy Aleksandr Y. , Boyd Alexander J. 
Published: March 2022

AbstractMany solar wind parameters correlate with one another, which complicates the causal‐effect studies of solar wind driving of the magnetosphere. Conditional mutual information (CMI) is used to untangle and isolate the effect of individual solar wind and magnetospheric drivers of the radiation belt electrons. The solar wind density (nsw) negatively correlates with electron phase space density (PSD; average energy ∼1.6 MeV) with time lag (τ) = 15 hr. The effect of nsw has been attributed to magnetopause shadowing or other loss mechanisms, but when the effect of solar wind velocity (Vsw) is removed, τ shifts to 7–11 hr, which is a more accurate time scale for this process. The peak correlation between Vsw and PSD shifts from τ = 30–50 to 44–56 hr, when the effect of nsw is removed. This suggests that the time scale for electron acceleration to 1–2 MeV is about 44–56 hr following Vsw enhancements. The effect of nsw is significant only at L* = 4.5–6 (L* > 6 is highly variable), whereas the effect of Vsw is significant only at L* = 3.5–6.5. The peak response of PSD to Vsw is the shortest and most significant at L* = 4.5–5.5. As time progresses, the peak response broadens and shifts to higher τ at higher and lower L*, consistent with local acceleration at L* = 4.5–5.5 followed by outward and inward diffusion. The outward radial diffusion time scale at L* = 5–6 is ∼40 hr per RE.
Modeling an Extreme Dust Deposition Event to the French Alpine Seasonal Snowpack in April 2018: Meteorological Context and Predictions of Dust Deposition
Authors: Baladima Foteini , Thomas Jennie L. , Voisin Didier , Dumont Marie , Junquas Clementine , Kumar Rajesh , Lavaysse Christophe , Marelle Louis , Parrington Mark , Flemming Johannes 
Published: March 2022

AbstractMineral dust is an important aerosol in the atmosphere and is known to reduce snow albedo upon deposition. Model predictions of dust deposition events in snow covered mountain regions are challenging due to the complexity of aerosol‐cloud interactions and the specifics of mountain meteorological systems. We use a case study of dust deposition between 30 March and 5 April 2018 to the French alpine snowpack to study the processes that control dust deposition to the seasonal snowpack. To understand processes controlling dust transport and deposition to snow, we use a combination of in situ observations at Col du Lautaret in the French Alps, satellite remote sensing, the Copernicus Atmosphere Monitoring Service (CAMS) reanalysis global atmospheric composition, and the regional model WRF‐Chem. Specifically, we investigate the role of increased model spatial resolution within WRF‐Chem in capturing mountain meteorology, precipitation, and predicted dust deposition. Regional model results are also compared to the reanalysis global CAMS products including aerosols in the atmosphere and predicted dust deposition fluxes. We conclude that predicted mountain meteorology (e.g., precipitation) is better with increased model resolution (3 × 3 km resolution WRF‐Chem domain). This improved meteorology has significant impacts on predicted dry and wet dust deposition to the alpine snowpack. Dry deposition is important in the western part of the French Alps at low altitudes, while wet deposition dominates over the complex higher altitude mountain terrain.
Preclinical assessment of combination therapy of EGFR tyrosine kinase inhibitors in a highly heterogeneous tumor model
Authors: Ikeuchi Hiroshi , Hirose Takeshi , Ikegami Masachika , Takamochi Kazuya , Suzuki Kenji , Mano Hiroyuki , Kohsaka Shinji 
Published: March 2022

AbstractThe development of tyrosine kinase inhibitors (TKIs) has improved the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current research priority is to provide viable treatments for patients who have drug-resistant EGFR mutations. We evaluated the drug sensitivity of various EGFR mutants to monotherapies and combination therapies of EGFR-TKIs. In vitro, the transforming potential and drug sensitivity of 357 EGFR variants were assessed. In vivo, we tested the sensitivity of EGFR variants to different regimens of EGFR-TKIs by examining changes in the proportion of each variant within the tumor. Out of 357 variants thoroughly examined for transforming activities, 144 (40.3%) and 282 (79.0%) transformed 3T3 and Ba/F3 cells, respectively. Among the latter variants, 50 (17.7%) were found to be resistant or only partly resistant to osimertinib or afatinib. Four of 25 afatinib-resistant variants (16%) were sensitive to osimertinib, whereas 25 of 46 osimertinib-resistant variants (54.3%) were sensitive to afatinib. Despite the lack of a synergistic impact, TKI combination treatment effectively reduced in vivo the heterogeneous tumors composed of 3T3 cells with different EGFR variants. Regimens starting with afatinib and subsequently switched to osimertinib suppressed tumor development more efficiently than the opposite combination. Combination EGFR-TKI treatment may decrease tumor growth and prevent the development of resistant variants. This work created an experimental model of a heterogeneous tumor to find the best combination therapy regimen and proposes a basic notion of EGFR-TKI combination therapy to enhance the prognosis of NSCLC patients.
Ventilation-to-perfusion relationships and right-to-left shunt during neonatal intensive care in infants with congenital diaphragmatic hernia
Authors: Dassios Theodore , Shareef Arattu Thodika Fahad M. , Williams Emma , Davenport Mark , Nicolaides Kypros H. , Greenough Anne 
Published: March 2022

Abstract
Background
We aimed to explore the postnatal evolution of ventilation/perfusion ratio (VA/Q) and right-to-left shunt in infants with congenital diaphragmatic hernia (CDH) and whether these indices predicted survival to discharge.

Methods
Retrospective cohort study at King’s College Hospital, London, UK of infants admitted with CDH in 10 years (2011–2021). The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the VA/Q and shunt in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death.

Results
Eighty-two infants with CDH (71 left-sided) were included with a median (IQR) gestation of 38.1(34.8–39.0) weeks. Fifty-three (65%) survived to discharge from neonatal care. The median (IQR) VA/Q in the first 24 h was lower in the deceased infants [0.09(0.07–0.12)] compared to the ones who survived [0.28(0.19–0.38), p < 0.001]. In the infants who survived, the VA/Q was lower in the first 24 h [0.28 (0.19–0.38)] compared to pre-operation [0.41 (0.3–0.49), p < 0.001] and lower pre-operation compared to pre-extubation [0.48 (0.39–0.55), p = 0.027]. The shunt was not different in infants who survived compared to the infants who did not.

Conclusions
Ventilation-to-perfusion ratio was lower in infants who died in the neonatal period compared to the ones that survived and improved in surviving infants over the immediate postnatal period.

Impact

The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the ventilation/perfusion ratio VA/Q in infants with congenital diaphragmatic hernia (CDH) in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death.

The VA/Q in the first 24 h of life was lower in the infants who did not survive to discharge from neonatal care compared to the ones who survived.

In the infants who survived, the VA/Q improved over the immediate postnatal period.

The non-invasive calculation of VA/Q can provide valuable information relating to survival to discharge.
Decreased efficacy of antimicrobial agents in a polymicrobial environment
Authors: O’Brien Thomas James , Figueroa Wendy , Welch Martin 
Published: March 2022

Abstract
The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.