bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Four-Day School Weeks on Physical Education Exposure and Childhood Obesity
Authors: Tomayko Emily J. , Gunter Katherine B. , Schuna John M. , Thompson Paul N. 
Published: August 2020

Background: Use of 4-day school weeks (FDSWs) as a cost-saving strategy has increased substantially as many US school districts face funding declines. However, the impacts of FDSWs on physical activity exposure and related outcomes are unknown. This study examined physical education (PE) exposure and childhood obesity prevalence in 4- versus 5-day Oregon schools; the authors hypothesized lower PE exposure and higher obesity in FDSW schools, given reduced school environment exposure. Methods: The authors utilized existing data from Oregon to compare 4- versus 5-day models: t tests compared mean school-level factors (PE exposure, time in school, enrollment, and demographics) and complex samples weighted t tests compared mean child-level obesity data for a state representative sample of first to third graders (N = 4625). Results: Enrollment, time in school, and student–teacher ratio were significantly lower in FDSW schools. FDSW schools provided significantly more PE, both in minutes (120 vs 101 min/wk in 4- vs 5-d schools, P < .01) and relative to total time in school (6.9% vs 5.0%, P < .0001). Obesity prevalence did not differ significantly between school models. Conclusion: Greater PE exposure in FDSW schools was observed, and it remains unknown whether differences in PE exposure contributed to obesity prevalence in this sample of students. Efforts to better understand how FDSWs impact physical activity, obesity risk, and related factors are needed.
Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study
Authors: DeBarmore Bailey , Longchamps Ryan J , Zhang Yiyi , Kalyani Rita R , Guallar Eliseo , Arking Dan E , Selvin Elizabeth , Young J Hunter 
Published: August 2020

IntroductionMitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.Research design and methodsWe assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.ResultsMean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.ConclusionsLower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.
Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome is caused by de novo mutations in protein kinase D1
Authors: Alter Svenja , Zimmer Andreas David , Park Misun , Gong Jianli , Caliebe Almuth , Fölster-Holst Regina , Torrelo Antonio , Colmenero Isabel , Steinberg Susan F , Fischer Judith 
Published: August 2020

BackgroundWe describe two unrelated patients who display similar clinical features including telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease.MethodsWe performed trio whole exome sequencing and functional analysis using in vitro kinase assays with recombinant proteins.ResultsWe identified two different de novo mutations in protein kinase D1 (PRKD1, NM_002742.2): c.1774G>C, p.(Gly592Arg) and c.1808G>A, p.(Arg603His), one in each patient. PRKD1 (PKD1, HGNC:9407) encodes a kinase that is a member of the protein kinase D (PKD) family of serine/threonine protein kinases involved in diverse cellular processes such as cell differentiation and proliferation and cell migration as well as vesicle transport and angiogenesis. Functional analysis using in vitro kinase assays with recombinant proteins showed that the mutation c.1808G>A, p.(Arg603His) represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The mutation c.1774G>C, p.(Gly592Arg) in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.ConclusionThe present cases represent a syndrome, which associates symptoms from several different organ systems: skin, teeth, bones and heart, caused by heterozygous de novo mutations in PRKD1 and expands the clinical spectrum of PRKD1 mutations, which have hitherto been linked to syndromic congenital heart disease and limb abnormalities.
Pathogenic variants inIMPG1cause autosomal dominant and autosomal recessive retinitis pigmentosa
Authors: Olivier Guillaume , Corton Marta , Intartaglia Daniela , Verbakel Sanne K , Sergouniotis Panagiotis I , Le Meur Guylène , Dhaenens Claire-Marie , Naacke Hélène , Avila-Fernández Almudena , Hoyng Carel B , Klevering Jeroen , Bocquet Béatrice , Roubertie Agathe , Sénéchal Audrey , Banfi Sandro , Muller Agnès , Hamel Christian L , Black Graeme C , Conte Ivan , Roosing Susanne , Zanlonghi Xavier , Ayuso Carmen , Meunier Isabelle , Manes Gaël 
Published: August 2020

BackgroundInherited retinal disorders are a clinically and genetically heterogeneous group of conditions and a major cause of visual impairment. Common disease subtypes include vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP). Despite the identification of over 90 genes associated with RP, conventional genetic testing fails to detect a molecular diagnosis in about one third of patients with RP.MethodsExome sequencing was carried out for identifying the disease-causing gene in a family with autosomal dominant RP. Gene panel testing and exome sequencing were performed in 596 RP and VMD families to identified additionalIMPG1variants. In vivo analysis in the medaka fish system by knockdown assays was performed to screenIMPG1possible pathogenic role.ResultsExome sequencing of a family with RP revealed a splice variant inIMPG1. Subsequently, the same variant was identified in individuals from two families with either RP or VMD. A retrospective study of patients with RP or VMD revealed eight additional families with different missense or nonsense variants inIMPG1. In addition, the clinical diagnosis of theIMPG1retinopathy-associated variant, originally described as benign concentric annular macular dystrophy, was also revised to RP with early macular involvement. Using morpholino-mediated ablation ofImpg1and its paralogImpg2in medaka fish, we confirmed a phenotype consistent with that observed in the families, including a decreased length of rod and cone photoreceptor outer segments.ConclusionThis study discusses a previously unreported association between monoallelic or biallelicIMPG1variants and RP. Notably, similar observations have been reported forIMPG2.
Can population BRCA screening be applied in non-Ashkenazi Jewish populations? Experience in Macau population
Authors: Qin Zixin , Kuok Cheong Nang , Dong Hui , Jiang Luhan , Zhang Li , Guo Maoni , Leong Hio Kuan , Wang Lei , Meng Grace , Wang San Ming 
Published: August 2020

BackgroundPathogenic mutation in BRCA genes causes high cancer risk. Identifying the mutation carriers plays key roles in preventing BRCA mutation-related cancer. Population screening has demonstrated its power for comprehensive identification of the mutation carriers. However, it is only recommended for the Ashkenazi Jewish population with high prevalence of three founder mutations, but not for non-Ashkenazi Jewish populations as the cost-effectiveness could be too low due to their lower mutation prevalence and lack of founder mutation. Population screening would not benefit the majority of the human population for BRCA mutation-related cancer prevention.MethodsWe used population BRCA screening in 6000 residents, 1% of the Macau population, an ethnic Chinese population with unique genetic, linguistic and cultural features, and its BRCA mutation has not been analysed before.ResultsWe called BRCA variants, identified 18 carriers with 14 pathogenic mutations and determined the prevalence of 0.29% in the population (95% CI 0.15% to 0.42%). We compared the testing cost between the Ashkenazi Jewish population, the Sephardi Jewish population and the Macau population, and observed only a few fold differences.ConclusionOur study shows that testing cost is not the most important factor in considering population BRCA screening, at least for the populations in the developed countries/regions, regardless of the status of mutation prevalence and founder mutation.
Biomarkers of Osimertinib Response in Patients with Refractory, EGFR-T790M–positive Non–Small Cell Lung Cancer and Central Nervous System Metastases: The APOLLO Study
Authors: Xing Ligang , Pan Yueyin , Shi Yuankai , Shu Yongqian , Feng Jifeng , Li Wei , Cao Lejie , Wang Lifeng , Gu Wei , Song Yong , Xing Puyuan , Liu Yutao , Gao Wen , Cui Jiuwei , Hu Nana , Li Rutian , Bao Hua , Shao Yang , Yu Jinming 
Published: August 2020

Abstract

Purpose:
Dynamic biomarker monitoring may inform pathways for treating EGFR-T790M–positive non–small cell lung cancer (NSCLC) and central nervous system (CNS) metastases with osimertinib. This study aimed to determine the efficacy and safety of osimertinib for real-world patients with EGFR-T790M NSCLC and CNS metastases and to explore potential circulating biomarkers of therapeutic response.

Patients and Methods:
APOLLO (ClinicalTrials.gov registration: NCT02972333) was a prospective, single-arm, open-label trial which ran from January 2017 to April 2019. Eligible patients had confirmed EGFR-T790M–positive NSCLC, prior treatment with an EGFR-tyrosine kinase inhibitor, and CNS metastases. All enrolled patients received oral osimertinib 80 mg once daily until disease progression or intolerable toxicity. Primary outcome was overall progression-free survival (PFSo) and secondary outcomes included objective response rate (ORR) and adverse events (AE). Exploratory biomarker analysis involved collection of plasma and cerebrospinal fluid (CSF) samples for next-generation sequencing and drug penetration analysis.

Results:
From January to September 2017, 38 patients were enrolled. After a median follow-up of 8.2 months (range, 0.07–15.6), 23 (60.5%) of 38 patients had disease progression or death. Median PFSo was 8.4 months [95% confidence interval (CI), 5.8–10.9]. Overall ORR was 39.4%. Twelve (31.6%) of 38 patients had ≥1 grade 3–4 AE. Median osimertinib CSF penetration rate was 31.7%. Patients with undetectable plasma EGFR mutations at week 6 had improved PFSo compared with those with detectable mutations (not reached vs. 4.5 months; 95% CI, 0.0–1.1; P &lt; 0.05).

Conclusions:
Osimertinib had potent activity against EGFR-T790M–positive NSCLC with CNS metastases. Dynamic monitoring of plasma EGFR may suffice for predicting clinical responses, mitigating the need for repeat CSF biopsy.
See related commentary by Marmarelis and Bauml, p. 6077
TIGIT Blockade and IL15 in Tumor Immunotherapy: Together is Better
Authors: Pietra Gabriella , Mingari Maria Cristina , Moretta Lorenzo 
Published: August 2020

Abstract
IL15 and TIGIT blockade enhances the natural killer (NK) cell–mediated activity against MHC-I–deficient melanoma both in vitro and in preclinical models. IL15-induced harnessing of NK cells, associated with their unleashing by TIGIT blockade, may represent a therapeutic approach for tumors, which lack HLA-I molecules thus escaping the CD8+ T cell–mediated control.
See related article by Chauvin et al., p. 5520
Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Mc Causland Finnian R. , Lefkowitz Martin P. , Claggett Brian , Anavekar Nagesh S. , Senni Michele , Gori Mauro , Jhund Pardeep S. , McGrath Martina M. , Packer Milton , Shi Victor , Van Veldhuisen Dirk J. , Zannad Faiez , Comin-Colet Josep , Pfeffer Marc A. , McMurray John J.V. , Solomon Scott D. 
Published: August 2020

Background:
In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction).

Methods:
In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope.

Results:

At randomization, eGFR was 63±19 mL·min
–1
·1.73 m
–
2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33–0.77];
P
=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min
–1
·1.73 m
–2
(
P
-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (–2.0 [95% CI, –2.2 to –1.9] versus –2.7 [95% CI, –2.8 to –2.5] mL·min
–1
·1.73 m
–2
per year).

Conclusions:
In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01920711.
New genera, species and combinations in the Pseudomicrocara Armstrong group (Coleoptera: Scirtidae) based on morphology supported by mitochondrial and nuclear gene sequence data
Authors: WATTS C.H.S. , COOPER S.J.B. , LIBONATTI M.L. 
Published: August 2020

The Australian Scirtidae genus Pseudomicrocara Armstrong, previously shown to be polyphyletic, is revised using both morphology and sequence data from the mitochondrial gene cytochrome oxidase subunit 1 and two nuclear genes, elongation factor 1-alpha and topoisomerase. Twenty-three genera, 16 of which are new, are recognised based on morphology, primarily of the mandibles and maxillary palpi, and male and female genitalia. Maximum likelihood and Bayesian phylogenetic analyses were used to examine relationships among species from 21 of the 23 recognised genera. Fifteen of the genera were recovered as distinct lineages. A further six, Accolabass Watts, Anocyphon gen. nov., Copiacyphon gen. nov., Nasutuscyphon gen. nov., Pseudomicrocara and Saprocyphon gen. nov. were considered to be genera based on both morphology and phylogenetic analysis but their species composition is uncertain and will require more work to confirm. The 17 new genera are fully described, keys are provided to all the genera in the Pseudomicrocara group, and to all the species in the genera Copiacyphon gen. nov., Spilotocyphon gen. nov., Accolabass Watts, Saltuscyphon gen. nov. and Vadumcyphon gen. nov. The male aedeagi of all new genera and species are illustrated, as are the female prehensors of some species. The following genera are described as new: Alpestriscyphon gen. nov., Anthocara gen. nov., Anocyphon gen. nov., Copiacyphon gen. nov., Furcacyphon gen. nov., Latuscara gen. nov., Pictacara gen. nov., Nasutuscyphon gen. nov., Nektriscyphon gen. nov., Pumiliocara gen. nov., Ruborcara gen. nov., Saltuscyphon gen. nov., Saprocyphon gen. nov., Sisyracyphon gen. nov., Spilotocyphon gen. nov., Tenebriocyphon gen. nov. and Vadumcyphon gen. nov. A total of 45 new combinations are proposed. The following species are described as new: Accolabass monteithi sp. nov.; Alpestriscyphon bartlefrere sp. nov., Al. spurgeon sp. nov.; Anocyphon lepus sp. nov.; Copiacyphon brindaleensis sp. nov., C. cardinalis sp. nov., C. dytikos sp. nov.; Pumiliocara peneparva sp. nov.; Ruborcara saintae sp. nov.; Saltuscyphon montanus sp. nov., Sal. teraniaensis sp. nov.; Saprocyphon bithongensis sp. nov.; Sisyracyphon brisbanensis sp. nov., S. bulburinensis sp. nov.; Spilotocyphon occidentalis sp. nov., Sp. orientalis sp. nov., Sp. zwicki sp. nov.; Vadumcyphon centralis sp. nov., V. rugosus sp. nov. A checklist of all Australian taxa in the redefined Pseudomicrocara group is included. Sequence data of the Argentinian species Pseudomicrocara antarctica (Fairmaire) is included. Phylogenetic analyses place this species as a distinct lineage within the Pseudomicrocara group.
Addition of Multilayer Urban Canopy Models to a Nonlocal Planetary Boundary Layer Parameterization and Evaluation Using Ideal and Real Cases
Authors: Hendricks Eric A. , Knievel Jason C. , Wang Yi 
Published: August 2020

AbstractThe multilayer urban canopy models (UCMs) building effect parameterization (BEP) and BEP + building energy model (BEM; a building energy model integrated in BEP) are added to the Yonsei University (YSU) planetary boundary layer (PBL) parameterization in the Weather Research and Forecasting (WRF) Model. The additions allow for the first analysis of the detailed effects of buildings on the urban boundary layer in a nonlocal closure scheme. The modified YSU PBL parameterization is compared with the other 1.5-order local PBL parameterizations that predict turbulent kinetic energy (TKE), Mellor–Yamada–Janjić and Bougeault–Lacarerre, using both ideal and real cases. The ideal-case evaluation confirms that BEP and BEP+BEM produce the expected results in the YSU PBL parameterization because the simulations are qualitatively similar to the TKE-based PBL parameterizations in which the multilayer UCMs have long existed. The modified YSU PBL parameterization is further evaluated for a real case. Similar to the ideal case, there are larger differences among the different UCMs (simple bulk scheme, BEP, and BEP+BEM) than across the PBL parameterizations when the UCM is held fixed. Based on evaluation against urban near-surface wind and temperature observations for this case, the BEP and BEP+BEM simulations are superior to the simple bulk scheme for each PBL parameterization.
Hydrometeor Shape Variability in Snowfall as Retrieved from Polarimetric Radar Measurements
Authors: Matrosov Sergey Y. , Ryzhkov Alexander V. , Maahn Maximilian , de Boer Gijs 
Published: August 2020

AbstractA polarimetric radar–based method for retrieving atmospheric ice particle shapes is applied to snowfall measurements by a scanning Ka-band radar deployed at Oliktok Point, Alaska (70.495°N, 149.883°W). The mean aspect ratio, which is defined by the hydrometeor minor-to-major dimension ratio for a spheroidal particle model, is retrieved as a particle shape parameter. The radar variables used for aspect ratio profile retrievals include reflectivity, differential reflectivity, and the copolar correlation coefficient. The retrievals indicate that hydrometeors with mean aspect ratios below 0.2–0.3 are usually present in regions with air temperatures warmer than approximately from −17° to −15°C, corresponding to a regime that has been shown to be favorable for growth of pristine ice crystals of planar habits. Radar reflectivities corresponding to the lowest mean aspect ratios are generally between −10 and 10 dBZ. For colder temperatures, mean aspect ratios are typically in a range between 0.3 and 0.8. There is a tendency for hydrometeor aspect ratios to increase as particles transition from altitudes in the temperature range from −17° to −15°C toward the ground. This increase is believed to result from aggregation and riming processes that cause particles to become more spherical and is associated with areas demonstrating differential reflectivity decreases with increasing reflectivity. Aspect ratio retrievals at the lowest altitudes are consistent with in situ measurements obtained using a surface-based multiangle snowflake camera. Pronounced gradients in particle aspect ratio profiles are observed at altitudes at which there is a change in the dominant hydrometeor species, as inferred by spectral measurements from a vertically pointing Doppler radar.
Inertia–Gravity Waves Breaking in the Middle Atmosphere at High Latitudes: Energy Transfer and Dissipation Tensor Anisotropy
Authors: Pestana Tiago , Thalhammer Matthias , Hickel Stefan 
Published: August 2020

Abstract
We present direct numerical simulations of inertia–gravity waves breaking in the middle–upper mesosphere. We consider two different altitudes, which correspond to the Reynolds number of 28 647 and 114 591 based on wavelength and buoyancy period. While the former was studied by Remmler et al., it is here repeated at a higher resolution and serves as a baseline for comparison with the high-Reynolds-number case. The simulations are designed based on the study of Fruman et al., and are initialized by superimposing primary and secondary perturbations to the convectively unstable base wave. Transient growth leads to an almost instantaneous wave breaking and secondary bursts of turbulence. We show that this process is characterized by the formation of fine flow structures that are predominantly located in the vicinity of the wave’s least stable point. During the wave breakdown, the energy dissipation rate tends to be an isotropic tensor, whereas it is strongly anisotropic in between the breaking events. We find that the vertical kinetic energy spectra exhibit a clear 5/3 scaling law at instants of intense energy dissipation rate and a cubic power law at calmer periods. The term-by-term energy budget reveals that the pressure term is the most important contributor to the global energy budget, as it couples the vertical and the horizontal kinetic energy. During the breaking events, the local energy transfer is predominantly from the mean to the fluctuating field and the kinetic energy production is in balance with the pseudo kinetic energy dissipation rate.