bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma
Authors: Kawauchi Daisuke , Ohno Makoto , Miyakita Yasuji , Takahashi Masamichi , Yanagisawa Shunsuke , Omura Takaki , Yoshida Akihiko , Kubo Yuko , Igaki Hiroshi , Ichimura Koichi , Narita Yoshitaka 
Published: August 2022

BACKGROUND:
Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear.

OBJECTIVE:
To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM.

METHODS:
Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined.

RESULTS:
Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores

90 was 48.6% and 29.6% in the early and late diagnosis groups (P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS

60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated).

CONCLUSION:
Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.
Comparison of Fusion versus Nonunion After 4-Level and 5-Level Anterior Cervical Diskectomy and Fusion With Anterior Plate Fixation
Authors: Bakare Adewale A. , Smitherman Adam D. , Fontes Ricardo B. V. , O'Toole John E. , Deutsch Harel , Traynelis Vincent C. 
Published: August 2022

BACKGROUND:
Nonunion remains a concern in multilevel anterior cervical discectomy and fusion (ACDF), yet there are limited data on nonunion after 4 to 5-level ACDF. In fact, the largest series on 4-level or 5-level ACDF focused specifically on the swallowing outcomes.

OBJECTIVE:
To assess nonunion after 4 to 5-level ACDF.

METHODS:
Forty-one patients treated with 4 to 5-level ACDF with minimum of 12-month radiographic follow-up were retrospectively reviewed. Nonunion was found in 25 patients (61%) and 42 levels (25%) and complete fusion in 16 (39%) patients and 126 levels (75%). The 2 groups were further compared.

RESULTS:
One-level nonunion was by far the most common pattern compared with multilevel nonunion. Nonunion occurred more frequently at the caudal than the cranial or middle segments (P < .0001). There were significantly more subsidence (P < .0001) and screw fractures/pullouts (P < .0001) in the nonunion compared with the fusion group. The symptomatic patients were significantly younger than the asymptomatic patients (P = .044). The symptomatic levels were significantly more than asymptomatic levels (P = .048). Equal proportion of patients implanted with allograft and polyetheretherketone had nonunion. However, there were markedly more nonunion than fused levels with allograft and more fused than nonunion levels with polyetheretherketone (P = .023). The reoperation rate was 24.4% and mostly due to nonunion. There were no reoperations within 90 days of the primary surgery.

CONCLUSION:
The nonunion rate for 4-level and 5-level ACDF may be higher than previously reported. Symptomatic nonunion remains a major reason for reoperation after multilevel ACDF. Baseline characteristics that negatively affect fusion may be obviated by careful patient selection.
TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration
Authors: Li Binbin , Brusman Liza , Dahlka Jacob , Niswander Lee A. 
Published: August 2022

ABSTRACT
Coordinated migration of the mesoderm is essential for accurate organization of the body plan during embryogenesis. However, little is known about how mesoderm migration influences posterior neural tube closure in mammals. Here, we show that spinal neural tube closure and lateral migration of the caudal paraxial mesoderm depend on transmembrane protein 132A (TMEM132A), a single-pass type I transmembrane protein, the function of which is not fully understood. Our study in Tmem132a-null mice and cell models demonstrates that TMEM132A regulates several integrins and downstream integrin pathway activation as well as cell migration behaviors. Our data also implicates mesoderm migration in elevation of the caudal neural folds and successful closure of the caudal neural tube. These results suggest a requirement for paraxial mesodermal cell migration during spinal neural tube closure, disruption of which may lead to spina bifida.
The dynamic proteome in Arabidopsis thaliana early embryogenesis
Authors: Huang Yingzhang , Zhou Limeng , Hou Chunhui , Guo Dianjing 
Published: August 2022

ABSTRACT
The morphology of the flowering plant is established during early embryogenesis. In recent years, many studies have focused on transcriptional profiling in plant embryogenesis, but the dynamic landscape of the Arabidopsis thaliana proteome remains elusive. In this study, Arabidopsis embryos at 2/4-cell, 8-cell, 16-cell, 32-cell, globular and heart stages were collected for nanoproteomic analysis. In total, 5386 proteins were identified. Of these, 1051 proteins were universally identified in all developmental stages and a range of 27 to 2154 proteins was found to be stage specific. These proteins could be grouped into eight clusters according to their expression levels. Gene Ontology enrichment analysis showed that genes involved in ribosome biogenesis and auxin-activated signalling were enriched during early embryogenesis, indicating that active translation and auxin signalling are important events in Arabidopsis embryo development. Combining RNA-sequencing data with the proteomics analysis, the correlation between mRNA and protein was evaluated. An overall positive correlation was found between mRNA and protein. This work provides a comprehensive landscape of the Arabidopsis proteome in early embryogenesis. Some important proteins/transcription factors identified through network analysis may serve as potential targets for future investigation.
Deltex modulates Dpp morphogen gradient formation and affects Dpp signaling in Drosophila
Authors: Sharma Vartika , Sarkar Bappi , Mutsuddi Mousumi , Mukherjee Ashim 
Published: August 2022

ABSTRACT
Deltex (Dx) is a context-dependent regulator of Notch signaling that can act in a non-canonical fashion by facilitating the endocytosis of the Notch receptor. In an RNAi-based modifier screen of kinases and phosphatases, we identified Thickveins (Tkv), the receptor of Decapentaplegic (Dpp), as one of the interactors of Dx. Dpp, a Drosophila homolog of TGF-β and bone morphogenetic proteins, acts as a morphogen to specify cell fate along the anterior–posterior axis of the wing. Tight regulation of Dpp signaling is thus indispensable for its proper functioning. Here, we present Dx as a novel modulator of Dpp signaling. We show evidence for the very first time that dx genetically interacts with dpp and its pathway components. Immunocytochemical analysis revealed that Dx colocalizes with Dpp and its receptor Tkv in Drosophila third-instar larval tissues. Furthermore, Dx was also seen to modulate the expression of dpp and its target genes, and we attribute this modulation to the involvement of Dx in the endocytosis and trafficking of Dpp. This study thus presents a whole new avenue of Dpp signaling regulation via the cytoplasmic protein Dx.
This article has an associated First Person interview with the first author of the paper.
Interaction between VPS13A and the XK scramblase is important for VPS13A function in humans
Authors: Park Jae-Sook , Hu Yiying , Hollingsworth Nancy M. , Miltenberger-Miltenyi Gabriel , Neiman Aaron M. 
Published: August 2022

ABSTRACT
VPS13 family proteins form conduits between the membranes of different organelles through which lipids are transferred. In humans, there are four VPS13 paralogs, and mutations in the genes encoding each of them are associated with different inherited disorders. VPS13 proteins contain multiple conserved domains. The Vps13 adaptor-binding (VAB) domain binds to adaptor proteins that recruit VPS13 to specific membrane contact sites. This work demonstrates the importance of a different domain in VPS13A function. The pleckstrin homology (PH) domain at the C-terminal region of VPS13A is required to form a complex with the XK scramblase and for the co-localization of VPS13A with XK within the cell. Alphafold modeling was used to predict an interaction surface between VPS13A and XK. Mutations in this region disrupt both complex formation and co-localization of the two proteins. Mutant VPS13A alleles found in patients with VPS13A disease truncate the PH domain. The phenotypic similarities between VPS13A disease and McLeod syndrome caused by mutations in VPS13A and XK, respectively, argue that loss of the VPS13A–XK complex is the basis of both diseases.
Early exposure to UV radiation causes telomere shortening and poorer condition later in life
Authors: Lundsgaard Niclas U. , Cramp Rebecca L. , Franklin Craig E. 
Published: August 2022

ABSTRACT
Determining the contribution of elevated ultraviolet-B radiation (UVBR; 280–315 nm) to amphibian population declines is being hindered by a lack of knowledge about how different acute UVBR exposure regimes during early life-history stages might affect post-metamorphic stages via long-term carryover effects. We acutely exposed tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a multi-factorial laboratory experiment, and then reared them to metamorphosis in the absence of UVBR to assess carryover effects in subsequent juvenile frogs. Dose and irradiance of acute UVBR exposure influenced carryover effects into metamorphosis in somewhat opposing manners. Higher doses of UVBR exposure in larvae yielded improved rates of metamorphosis. However, exposure at a high irradiance resulted in frogs metamorphosing smaller in size and in poorer condition than frogs exposed to low and medium irradiance UVBR as larvae. We also demonstrate some of the first empirical evidence of UVBR-induced telomere shortening in vivo, which is one possible mechanism for life-history trade-offs impacting condition post-metamorphosis. These findings contribute to our understanding of how acute UVBR exposure regimes in early life affect later life-history stages, which has implications for how this stressor may shape population dynamics.
Descriptive analysis of clinical and laboratory findings in relation to changes in SARS-CoV-2 viral dynamics and cyclic threshold: a retrospective, single center observational study in patients treated with Hydroxychloroquine/Azithromycin combination therapy
Authors: Alamri Maha M. , Devol Edward B. , Al-Otaibi Anwar B. , Albaiz Faisal A. , Alabdely Mayyadah H. , Althawadi Sahar I. , Mutabagani Maysoon S. , Alhamlan Fatimah S. , Alrabiah Fahad A. , Almaghrabi Reem S. 
Published: August 2022

Background: Cases of undiagnosed pneumonia have emerged, and sequencing of respiratory samples indicated the presence of SARS-CoV-2 causing COVID-19. Patients with higher viral load and lower Ct values tend to have progressive disease and severe lung injury. The objective of this study is to describe the clinical manifestation and disease outcomes of COVID-19 patients in relation to their Ct values. Methods: A retrospective, single center observational study was performed, including patients admitted to King Faisal Specialist Hospital and Research Centre (KFSH&RC) Riyadh between March 1st-29th, 2020 and have a confirmed diagnosis of COVID-19. The Ct value was identified to determine the viral load. All patients were treated according to KFSH&RC guidelines. Patients were divided into HCQ/AZI and non HCQ/AZI treated groups. Results: There were many days where Ct values were not available. An attempt at imputing information for missing Ct values was made using logic. The logic leads to an ordinal Ct score 1, 2, 3, or 4. As a result, complete Ct score profiles were available. There was no evidence of statistically significant difference between the two groups in regard to clinical severity, duration to negative test or changes in Ct values. Conclusion: There is little knowledge known to the time profile of Ct values and their relation to disease course of COVID-19. This study provides insight on how Ct values might be used to determine treatment efficacy. As it might be difficult to obtain Ct values at all times, this study provides an imputation method that may be used with conservative statistical assumptions for analyses of Ct profiles.
Adoption of FasTrak on San Francisco Bay Area Bridges: Impact of Operations Research Models in Relieving Congestion
Authors: Bollapragada Ramesh , Kakar Venoo , Goodwin John , Fremier Andrew 
Published: August 2022

Bay Area toll bridges are the main transportation link across the nine-county San Francisco Bay Area. These bridges experience extreme congestion and become bottlenecks during peak hours with long backups at the toll plazas. A solution to ensure smooth vehicle throughput at toll plazas is the widespread adoption of the electronic toll collection system called FasTrak. However, the FasTrak system has experienced low usage rates since its inception relative to other toll collection systems in the country. Forecasting, marketing, and operations research models were utilized to make recommendations and collaborate with transportation authorities to increase FasTrak usage during peak hours (5–10 a.m. and 3–7 p.m.) to address traffic congestion. After these recommendations were implemented, FasTrak usage increased from 40% in 2006 to the long-term target of 70% by 2016. This paper presents a synthesis of the challenges and the implementation of the FasTrak Strategic Plan. Furthermore, econometric models are presented that capture the effect on traffic volumes of increased FasTrak usage achieved through congestion pricing. Saved travel time resulted in productivity gains of approximately $569 million per year. This study contributes to an understanding of the role of effective transportation policies in reducing congestion and improving productivity. History: This paper was refereed. Supplemental Material: The online appendix is available at https://doi.org/10.1287/inte.2022.1127 .
Numerical simulation of scalar wave scattering by a circular cylinder buried in a planar substrate
Authors: Tsermaa Baatarchuluun , Kim Jin Seung , Park Byong Chon , Myung-Whun Kim 
Published: August 2022

We report numerical simulation results based on rigorous analytic solutions of scalar wave scattering caused by a cylinder buried in a planar substrate. As there are multiple interactions between the planar substrate and the cylinder, theoretical solutions were expressed in the form of coupled sets of infinite series, with each term within the series explicitly reflecting the effect of multiple scattering of increasing order. We determined the near- and far-field distributions of (1) the reflected field in the air, (2) the scattered and transmitted fields in the substrate, and (3) the transmitted field within the cylinder. Our results indicate that the effects of higher-order multiple scattering depend on the size, location, and refractive index of the cylinder, especially in the near-field region. The simulation is generalizable, as it places no restrictions on the physical and geometrical qualities of the cylinder or the planar substrate.
Lipid levels in midlife and risk of atrial fibrillation over 3 decades—Experience from the Swedish AMORIS cohort: A cohort study
Authors: Ding Mozhu , Wennberg Alexandra , Gigante Bruna , Walldius Göran , Hammar Niklas , Modig Karin 
Published: August 2022

Background
The role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF.

Methods and findings
This population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding.

Conclusions
High TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk.
Association between serum uric acid levels and colonic diverticulosis in terms of sex
Authors: Hu Je-Ming , Chang Yu-Tien , Shih Chi-Wei , Hsu Chih-Hsiung , Lin Tzu-Chiao , Lai Chung-Yu , Lin Ming-Hsun , Chen Wei-Liang 
Published: August 2022

Background
The association between elevated serum uric acid (UA) levels and the risk of developing colonic diverticulosis has not yet been investigated. Thus, this cross-sectional study aimed to examine this correlation in individuals from Taiwan.

Methods
From Jan. 1, 2010, to Dec. 31, 2016., approximately 5,605 patients (aged >20 years) from Tri-Service General Hospital who met the inclusion criteria according to colonoscopy and laboratory test findings were included in this research. The correlation between serum UA levels and colonic diverticulosis was investigated via regression analyses.

Results
Participants with elevated serum UA levels were at a higher risk of colonic diverticulosis. The area under the curve for serum UA levels was significantly higher in women than in men (0.651 [95% confidence interval: 0.596–0.707] vs. 0.55 [0.507–0.593]). There were specific trends in female-specific indicators for colonic diverticulosis across increasing quartiles of serum UA levels.

Conclusions
Patients with elevated serum UA levels should be cautious regarding the development of colonic diverticulosis disorder in female. Moreover, prospective studies may provide additional information on the relationship between elevated serum UA levels and colonic diverticulosis.
What matters most to patients with severe aortic stenosis when choosing treatment? Framing the conversation for shared decision making
Authors: Col Nananda F. , Otero Diana , Lindman Brian R. , Horne Aaron , Levack Melissa M. , Ngo Long , Goodloe Kimberly , Strong Susan , Kaplan Elvin , Beaudry Melissa , Coylewright Megan 
Published: August 2022

Background
Guidelines recommend including the patient’s values and preferences when choosing treatment for severe aortic stenosis (sAS). However, little is known about what matters most to patients as they develop treatment preferences. Our objective was to identify, prioritize, and organize patient-reported goals and features of treatment for sAS.

Methods
This multi-center mixed-methods study conducted structured focus groups using the nominal group technique to identify patients’ most important treatment goals and features. Patients separately rated and grouped those items using card sorting techniques. Multidimensional scaling and hierarchical cluster analyses generated a cognitive map and clusters.

Results
51 adults with sAS and 3 caregivers with experience choosing treatment (age 36–92 years) were included. Participants were referred from multiple health centers across the U.S. and online. Eight nominal group meetings generated 32 unique treatment goals and 46 treatment features, which were grouped into 10 clusters of goals and 11 clusters of features. The most important clusters were: 1) trust in the healthcare team, 2) having good information about options, and 3) long-term outlook. Other clusters addressed the need for and urgency of treatment, being independent and active, overall health, quality of life, family and friends, recovery, homecare, and the process of decision-making.

Conclusions
These patient-reported items addressed the impact of the treatment decision on the lives of patients and their families from the time of decision-making through recovery, homecare, and beyond. Many attributes had not been previously reported for sAS. The goals and features that patients’ value, and the relative importance that they attach to them, differ from those reported in clinical trials and vary substantially from one individual to another. These findings are being used to design a shared decision-making tool to help patients and their clinicians choose a treatment that aligns with the patients’ priorities.

Trial registration
ClinicalTrials.gov, Trial ID: NCT04755426, Trial URL https://clinicaltrials.gov/ct2/show/NCT04755426.