bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fog type classification using a modified Richardson number for Christchurch, New Zealand
Authors: Lin Dongqi , Katurji Marwan , Revell Laura E. , Khan Basit , Osborne Neal , Soltanzadeh Iman , Kremser Stefanie 
Published: June 2022

AbstractSituated on a coastal plain between the Southern Alps and Banks Peninsula, Christchurch, New Zealand, experiences around 49 fog days every year. Given its complex topography, accurate fog forecasting is difficult at Christchurch International Airport (CHA). Climatological analysis of local fog events is an important first step to gain insight into the processes involved in the fog lifecycle. In this study, fog events were identified using 12 years of meteorological observations from an automatic weather station situated at CHA. A novel fog type classification method was developed using the modified Richardson number (MRi). The MRi fog type classification method assesses the local dynamic stability of a 1.25 m shallow layer of near‐surface air. Here, the MRi is used as a quantitative index to classify advection fog, advection–radiation fog, and radiation fog. Vertical gradients of air temperature and wind speed were derived for prefog and fog periods, and a number of criteria were applied to the MRi for the fog type classification. The fog type classification results were examined in correspondence with the derived fog intensity, duration, diurnal and seasonal variability of frequency of occurrences, and synoptic and local wind flows. In agreement with other fog studies across the world, fog occurs most frequently during local winter and spring. Radiation fog is the predominant type of fog identified at CHA, and its formation and development usually coincide with the local drainage northwesterlies. This study is the first to use long‐term observational data to investigate the fog climatology and typology at CHA in detail. The fog climatological characteristics presented in this study will serve as the basis of future fog studies in Christchurch. The presented MRi fog type classification method can potentially be used in fog characteristic studies worldwide.
New‐onset and persistent neurological and psychiatric sequelae of COVID‐19 compared to influenza: A retrospective cohort study in a large New York City healthcare network
Authors: Iosifescu Andrei L. , Hoogenboom Wouter S. , Buczek Alexandra J. , Fleysher Roman , Duong Tim Q. 
Published: June 2022

AbstractObjectivesNeurological and neuropsychiatric manifestations of post‐acute SARS‐CoV‐2 infection (neuro‐PASC) are common among COVID‐19 survivors, but it is unknown how neuro‐PASC differs from influenza‐related neuro‐sequelae. This study investigated the clinical characteristics of COVID‐19 patients with and without new‐onset neuro‐PASC, and of flu patients with similar symptoms.MethodsWe retrospectively screened 18,811 COVID‐19 patients and 5772 flu patients between January 2020 and June 2021 for the presence of new‐onset neuro‐sequelae that persisted at least 2 weeks past the date of COVID‐19 or flu diagnosis.ResultsWe observed 388 COVID‐19 patients with neuro‐PASC versus 149 flu patients with neuro‐sequelae. Common neuro‐PASC symptoms were anxiety (30%), depression (27%), dizziness (22%), altered mental status (17%), chronic headaches (17%), and nausea (11%). The average time to neuro‐PASC onset was 138 days, with hospitalized patients reporting earlier onset than non‐hospitalized patients. Neuro‐PASC was associated with female sex and older age (p < 0.05), but not race, ethnicity, most comorbidities, or COVID‐19 disease severity (p > 0.05). Compared to flu patients, COVID‐19 patients were older, exhibited higher incidence of altered mental status, developed symptoms more quickly, and were prescribed psychiatric drugs more often (p < 0.05).ConclusionsThis study provides additional insights into neuro‐PASC risk factors and differentiates between post‐COVID‐19 and post‐flu neuro‐sequelae.
National prescription patterns of antidepressants among patients with amyotrophic lateral sclerosis: An analysis of the Korean National Health Insurance database
Authors: Park C. Hyung Keun , Choi Seok‐Jin , Kim Ye‐Jee , Hong Yoon‐Ho , Sung Jung‐Joon 
Published: June 2022

AbstractIntroduction/AimsThe current status of antidepressant use in patients with amyotrophic lateral sclerosis (ALS), such as the prevalence and factors associated with it, has not been systematically investigated. We aimed to analyze the prevalence and patterns of antidepressant prescriptions in patients with ALS and depression, and to identify factors associated with antidepressant prescriptions after the diagnosis of ALS.MethodsThe data of patients with ALS and the prescription of antidepressants were retrieved from the Korean National Health Insurance claims data. A multivariate logistic regression model was used to identify factors associated with antidepressant prescriptions.ResultsIn total, 533 of 2955 patients had depressive disorders, and 426 were prescribed antidepressants. Selective serotonin reuptake inhibitors and tricyclic antidepressants were the most frequently prescribed drugs. Adjusted odds ratios (ORs) were 1.379 for the prescription of antidepressants in females. For various age groups, compared with those aged 80 years and older, adjusted ORs were 1.889 for those in their 70s, 2.319 for those in their 60s, 2.872 for those in their 50s, 2.854 for those in their 40s, and 3.363 for those under 40 years of age. Adjusted ORs were 1.662 for patients with a history of a psychiatric disorder and 1.861 for those with a history of psychiatric pharmacotherapy (all P < .05).DiscussionMost patients with ALS who had depression received antidepressant prescriptions. In young females with a previous psychiatric disorder or pharmacotherapy, an in‐depth evaluation for a depressive disorder should be performed.
Genome‐wide association studies identify putative pleiotropic locus mediating drought tolerance in sorghum
Authors: Maina Fanna , Harou Abdou , Hamidou Falalou , Morris Geoffrey P. 
Published: June 2022

AbstractDrought is a key constraint on plant productivity and threat to food security. Sorghum (Sorghum bicolor L. Moench), a global staple food and forage crop, is among the most drought‐adapted cereal crops, but its adaptation is not yet well understood. This study aims to better understand the genetic basis of preflowering drought in sorghum and identify loci underlying variation in water use and yield components under drought. A panel of 219 diverse sorghum from West Africa was phenotyped for yield components and water use in an outdoor large‐tube lysimeter system under well‐watered (WW) versus a preflowering drought water‐stressed (WS) treatment. The experimental system was validated based on characteristic drought response in international drought tolerant check genotypes and genome‐wide association studies (GWAS) that mapped the major height locus at QHT7.1 and Dw3. GWAS further identified marker trait associations (MTAs) for drought‐related traits (plant height, flowering time, forage biomass, grain weight, water use) that each explained 7–70% of phenotypic variance. Most MTAs for drought‐related traits correspond to loci not previously reported, but some MTA for forage biomass and grain weight under WS co‐localized with staygreen post‐flowering drought tolerance loci (Stg3a and Stg4). A globally common allele at S7_50055849 is associated with several yield components under drought, suggesting that it tags a major pleiotropic variant controlling assimilate partitioning to grain versus vegetative biomass. The GWAS revealed oligogenic variants for drought tolerance in sorghum landraces, which could be used as trait predictive markers for improved drought adaptation.
Integration of Complex Geometry Gun Propellant Form Function Calculation and Geometry Optimization
Authors: Wang Moru , Jin Guorui , Zhou Yongrong , Nan Fengqiang , Lin Xiangyang , He Weidong 
Published: June 2022

AbstractTo take full advantage of the additive manufacturing technology, an integrated and efficient approach of complex geometry gun propellant form function calculation and geometry optimization design based on Grasshopper (GH) software was proposed as a first attempt to obtain the closed‐loop of geometric optimization forward design with performance as the goal and algorithm as the means. The burning surface regression simulation and form function calculation of the entire multi‐perforation gun propellant family, multi‐perforation web thickness uneven gun propellant family, mixed gun propellant charges were demonstrated by using the parametric model of GH software. With the highest combustion progressivity as the optimization objective, the genetic algorithm in GH software was used to geometrically optimize the parametric model of multi‐perforation gun propellant family, and then the entire multi‐perforation with ball gun propellant family was obtained. The closed vessel test result showed that the form function calculated by the GH approach was in better agreement with the test curve than that of the analytic method. The integral form function of the mixed gun propellant charges was calculated firstly and proved by the interior ballistic performance calculation. The combustion progressivity of rosette‐shaped 19‐perf with ball gun propellant was significantly improved compared with that before geometry optimization, with the ball‐tube, ball‐ball, and ball‐ball‐ball structure increasing by about 15.0 %, 17.7 %, and 17.7 %, respectively. The integrated and efficient approach was dynamically visualized in real‐time and required no learning of conventional scripting‐type programming, providing the basis for the design and application of gun propellant with any complex geometry.
Odd one out? Functional tuning of Zymomonas mobilis pyruvate kinase is narrower than its allosteric, human counterpart
Authors: Page Braelyn M. , Martin Tyler A. , Wright Collette L. , Fenton Lauren A. , Villar Maite T. , Tang Qingling , Artigues Antonio , Lamb Audrey , Fenton Aron W. , Swint‐Kruse Liskin 
Published: June 2022

AbstractVarious protein properties are often illuminated using sequence comparisons of protein homologs. For example, in analyses of the pyruvate kinase multiple sequence alignment, the set of positions that changed during speciation (“phylogenetic” positions) were enriched for “rheostat” positions in human liver pyruvate kinase (hLPYK). (Rheostat positions are those which, when substituted with various amino acids, yield a range of functional outcomes). However, the correlation was moderate, which could result from multiple biophysical constraints acting on the same position during evolution and/or various sources of noise. To further examine this correlation, we here tested Zymomonas mobilis PYK (ZmPYK), which has <65% sequence identity to any other PYK sequence. Twenty‐six ZmPYK positions were selected based on their phylogenetic scores, substituted with multiple amino acids, and assessed for changes in Kapp‐PEP. Although we expected to identify multiple, strong rheostat positions, only one moderate rheostat position was detected. Instead, nearly half of the 271 ZmPYK variants were inactive and most others showed near wild‐type function. Indeed, for the active ZmPYK variants, the total range of Kapp,PEP values (”tunability”) was 40‐fold less than that observed for hLPYK variants. The combined functional studies and sequence comparisons suggest that ZmPYK has evolved functional and/or structural attributes that differ from the rest of the family. We hypothesize that including such “orphan” sequences in MSA analyses obscures the correlations used to predict rheostat positions. Finally, results raise the intriguing biophysical question as to how the same protein fold can support rheostat positions in one homolog but not another.
Evaluation of residue variability in a conformation‐specific context and during evolutionary sequence reconstruction narrows drug resistance selection in Abl1 tyrosine kinase
Authors: Otsuka Felipe A. M. , Bjelic Sinisa 
Published: June 2022

AbstractDiseases with readily available therapies may eventually prevail against the specific treatment by the acquisition of resistance. The constitutively active Abl1 tyrosine kinase known to cause chronic myeloid leukemia is an example, where patients may experience relapse after small inhibitor drug treatment. Mutations in the Abl1 tyrosine kinase domain (Abl1‐KD) are a critical source of resistance and their emergence depends on the conformational states that have been observed experimentally: the inactive state, the active state, and the intermediate inactive state that resembles Src kinase. Understanding how resistant positions and amino acid identities are determined by selection pressure during drug treatment is necessary to improve future drug development or treatment decisions. We carry out in silico site‐saturation mutagenesis over the Abl1‐KD structure in a conformational context to evaluate the in situ and conformational stability energy upon mutation. Out of the 11 studied resistant positions, we determined that 7 of the resistant mutations favored the active conformation of Abl1‐KD with respect to the inactive state. When, instead, the sequence optimization was modeled simultaneously at resistant positions, we recovered five known resistant mutations in the active conformation. These results suggested that the Abl1 resistance mechanism targeted substitutions that favored the active conformation. Further sequence variability, explored by ancestral reconstruction in Abl1‐KD, showed that neutral genetic drift, with respect to amino acid variability, was specifically diminished in the resistant positions. Since resistant mutations are susceptible to chance with a certain probability of fixation, combining methodologies outlined here may narrow and limit the available sequence space for resistance to emerge, resulting in more robust therapeutic treatments over time.
3,4‐Dihydroxyphenylethanol and 3,4‐dihydroxyphenylacetic acid affect the aggregation process of E46K variant of α‐synuclein at different extent: Insights into the interplay between protein dynamics and catechol effect
Authors: Fongaro Benedetta , Cappelletto Elia , Sosic Alice , Spolaore Barbara , Polverino de Laureto Patrizia 
Published: June 2022

AbstractParkinson's disease (PD) is a chronic multifactorial disease, whose etiology is not completely understood. The amyloid aggregation of α‐synuclein (Syn) is considered a major cause in the development of the disease. The presence of genetic mutations can boost the aggregation of the protein and the likelihood to develop PD. These mutations can lead to early onset (A30P, E46K, and A53T) or late‐onset (H50Q) forms of PD. The disease is also linked to an increase in oxidative stress and altered levels of dopamine metabolites. The molecular interaction of these molecules with Syn has been previously studied, while their effect on the pathological mutant structure and function is not completely clarified. By using biochemical and biophysical approaches, here we have studied the interaction of the familial variant E46K with two dopamine‐derived catechols, 3,4‐dihydroxyphenylacetic acid and 3,4‐dihydroxyphenylethanol. We show that the presence of these catechols causes a decrease in the formation of amyloid fibrils in a dose‐dependent manner. Native‐ and Hydrogen/deuterium exchange‐mass spectrometry (HDX‐MS) provide evidence that this effect is strongly conformation dependent. Indeed, these molecules interact differently with the interconverting conformers of Syn and its familial variant E46K in solution, selecting the most prone‐to‐aggregation one, confining it into an off‐pathway oligomer. These findings suggest that catechols could be a molecular scaffold for the design of compounds potentially useful in the treatment of Parkinson's disease and related conditions.
Beyond structure: Deciphering site‐specific dynamics in proteins from double histidine‐based EPR measurements
Authors: Singewald Kevin , Wilkinson James A. , Hasanbasri Zikri , Saxena Sunil 
Published: June 2022

AbstractSite‐specific dynamics in proteins are at the heart of protein function. While electron paramagnetic resonance (EPR) has potential to measure dynamics in large protein complexes, the reliance on flexible nitroxide labels is limitating especially for the accurate measurement of site‐specific β‐sheet dynamics. Here, we employed EPR spectroscopy to measure site‐specific dynamics across the surface of a protein, GB1. Through the use of the double Histidine (dHis) motif, which enables labeling with a Cu(II) – nitrilotriacetic acid (NTA) complex, dynamics information was obtained for both α‐helical and β‐sheet sites. Spectral simulations of the resulting CW‐EPR report unique site‐specific fluctuations across the surface of GB1. Additionally, we performed molecular dynamics (MD) simulations to complement the EPR data. The dynamics observed from MD agree with the EPR results. Furthermore, we observe small changes in gǁ values for different sites, which may be due to small differences in coordination geometry and/or local electrostatics of the site. Taken together, this work expands the utility of Cu(II)NTA‐based EPR measurements to probe information beyond distance constraints.
The sodium‐glucose co‐transporter 2 inhibitor tofogliflozin suppresses atherosclerosis through glucose lowering in ApoE‐deficient mice with streptozotocin‐induced diabetes
Authors: Iwamoto Masahiko , Kubota Tetsuya , Sakurai Yoshitaka , Wada Nobuhiro , Shioda Seiji , Yamauchi Toshimasa , Kadowaki Takashi , Kubota Naoto 
Published: June 2022

AbstractEpidemiological and animal studies have revealed that sodium‐glucose cotransporter 2 (SGLT2) inhibitors suppress cardiovascular events in subjects with type 2 diabetes and atherosclerosis in animal models of diabetes. However, it still remains unclear if the anti‐atherosclerotic effect of SGLT2 inhibitors is entirely dependent on their glucose‐lowering effect. Tofogliflozin, a highly specific SGLT2 inhibitor, was administrated to apolipoprotein‐E‐deficient (ApoEKO) with streptozotocin (STZ)‐induced diabetes and nondiabetic ApoEKO mice. After 6 weeks, samples were collected to investigate the histological changes and peritoneal macrophage inflammatory cytokine levels. Tofogliflozin suppressed atherosclerosis in the diabetic ApoEKO mice. The atherosclerosis lesion areas and accumulation of macrophages in these areas were reduced by tofogliflozin treatment. The expression levels of interleukin (IL)‐1β and IL‐6 in the peritoneal macrophages were significantly suppressed in the tofogliflozin‐treated diabetic ApoEKO mice. Tofogliflozin treatment failed to inhibit atherosclerosis in the nondiabetic ApoEKO mice. No significant difference in the anti‐atherosclerotic effects of insulin and tofogliflozin was observed between diabetic ApoEKO mice with equivalent degrees of glycemic control achieved with the two treatments. Insulin treatment significantly reduced the IL‐1β and IL‐6 expression levels in the peritoneal macrophages of the diabetic ApoEKO mice. Significant decrease of the LPS‐stimulated IL‐1β concentrations was also observed in the conditioned medium of the peritoneal macrophages collected from insulin‐ and tofogliflozin‐treated diabetic ApoEKO mice. These results suggest that tofogliflozin suppresses atherosclerosis by improving glucose intolerance associated with inhibition of inflammation. Tofogliflozin suppresses atherosclerosis in ApoEKO mice with STZ‐induced diabetes via its glucose‐lowering effect.
Muscle mass change using linear measurement analysis after nephrectomy for pT3 and pT4 renal cell carcinoma is associated with mortality
Authors: Medline Alexandra , Midenberg Eric , Patil Dattatraya , Evans Sean , Vettikattu Nikhil , Kamal Fatima , Ogan Kenneth , Psutka Sarah P. , Bilen Mehmet Asim , Master Viraj A. 
Published: June 2022

AbstractBackgroundPreoperative skeletal muscle deficiency is an established risk factor for poor survival outcomes in patients with renal cell carcinoma (RCC). However, given the dynamic nature of skeletal muscle associated with malignancy, there is a need to evaluate the prognostic benefit of muscle area change from the preoperative to postoperative period. We hypothesize that an improvement in muscle area following nephrectomy, measured by linear segmentation of L3 psoas and paraspinal musculature, is associated with improvement in overall survival (OS) and cancer specific survival (CSS) for patients with pT3 and pT4 RCC.MethodsWe retrospectively analysed 270 pT3 and pT4 RCC patients who underwent nephrectomy from March 2004 to February 2020 with available preoperative and postoperative axial CT or MRI studies segmented at the L3 vertebrae. The majority were N0 (79%) and M0 (68%). Psoas and paraspinal muscles were measured bilaterally using a validated digital ruler tool. Total muscle area (TMA) was calculated by aggregating the area of all four muscles and total muscle area index (TMI) by dividing the TMA by height squared (m2). The prognostic value of postoperative muscle improvement, defined as any increase in muscle area index, was analysed using Kaplan–Meier and Cox proportional stepwise hazard models.ResultsMedian time between preoperative scans and surgery was approximately 22 days and between surgery and postoperative scans 172 days. One hundred twenty‐one patients (44.8%) had an increase in total muscle area index post‐nephrectomy (IQR = 33.4; P ≤ 0.0001). On Kaplan–Meier analysis, postoperative improvement in TMI was associated with decreased odds of mortality (P = 0.0024) with a median follow‐up of 38.6 months. In a multivariable Cox regression analysis, improvement of TMI was associated with increased OS (HR = 0.52, 95% CI 0.35–0.78, P < 0.001) and increased CSS (HR = 0.55, 95% CI 0.32–0.94, P = 0.030). A 5% or more improvement in TMI was also associated with increased OS (HR = 0.53, 95% CI 0.34–0.84, P = 0.006) and increased CSS (HR = 0.46, 95% CI 0.24–0.86, P = 0.015).ConclusionsAny improvement in TMI between preoperative and initial postoperative imaging after nephrectomy was associated with increased OS and CSS in patients with pT3 and pT4 RCC. Perioperative linear segmentation is an efficient tool that may improve current prognostication methods and can be performed on any imaging software platform.