bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning‐based model for diagnosing Alzheimer's disease and tauopathies
Authors: Koga Shunsuke , Ikeda Akihiro , Dickson Dennis W. 
Published: August 2021

AbstractAimsThis study aimed to develop a deep learning‐based model for differentiating tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease (PiD), based on tau‐immunostained digital slide images.MethodsWe trained the YOLOv3 object detection algorithm to detect five tau lesion types: neuronal inclusions, neuritic plaques, tufted astrocytes, astrocytic plaques and coiled bodies. We used 2522 digital slide images of CP13‐immunostained slides of the motor cortex from 10 cases each of AD, PSP and CBD for training. Data augmentation was performed to increase the size of the training dataset. We next constructed random forest classifiers using the quantitative burdens of each tau lesion from motor cortex, caudate nucleus and superior frontal gyrus, ascertained from the object detection model. We split 120 cases (32 AD, 36 PSP, 31 CBD and 21 PiD) into training (90 cases) and test (30 cases) sets to train random forest classifiers.ResultsThe resultant random forest classifier achieved an average test score of 0.97, indicating that 29 out of 30 cases were correctly diagnosed. A validation study using hold‐out datasets of CP13‐ and AT8‐stained slides from 50 cases (10 AD, 17 PSP, 13 CBD and 10 PiD) showed >92% (without data augmentation) and >95% (with data augmentation) diagnostic accuracy in both CP13‐ and AT8‐stained slides.ConclusionOur diagnostic model trained with CP13 also works for AT8; therefore, our diagnostic tool can be potentially used by other investigators and may assist medical decision‐making in neuropathological diagnoses of tauopathies.
A case of rheumatoid meningoencephalitis induced by pembrolizumab
Authors: Matsuoka Chika , Omote Yoshio , Kawahara Yuko , Sasaki Ryo , Matsumoto Namiko , Tadokoro Ko , Taira Yuki , Takemoto Mami , Morihara Ryuta , Yamashita Toru , Abe Koji 
Published: August 2021

AbstractImmune checkpoint inhibitors occasionally cause various side effects, but the occurrence of a severe immune‐related adverse event (irAE) is rare in neurology. We report on a 56‐year‐old woman who suffered from rheumatoid arthritis and recurrent uterine cancer. After treatment with pembrolizumab, she showed visual disturbance followed by acute fever and consciousness disturbance with high‐intensity lesions around the midbrain aqueduct and bilateral caudate heads on FLAIR images of a brain MRI. Her symptoms improved after steroid therapy. However, symptoms relapsed leading to an elevation of the anti‐CCP antibody index. Pembrolizumab‐induced rheumatoid meningoencephalitis was suspected, so additional steroid therapy was provided. This improved her symptoms, turning the anti‐CCP antibody index negative. The present case is the first case of rheumatoid meningoencephalitis induced by pembrolizumab. The combination of MRI findings and elevated anti‐CCP index seems useful for diagnosing rheumatoid meningoencephalitis.
Successful treatment of anti‐GAD antibody‐associated autoimmune cerebellar ataxia with combined immunotherapies
Authors: Omote Yoshio , Matsuoka Chika , Sasaki Ryo , Hishikawa Nozomi , Kawahara Yuko , Nomura Emi , Matsumoto Namiko , Taira Yuki , Takemoto Mami , Morihara Ryuta , Yamashita Toru , Abe Koji 
Published: August 2021

AbstractAnti‐glutamic acid decarboxylase (GAD) antibody (Ab)‐associated autoimmune cerebellar ataxia (CA) is a rare neurological disorder, and a standardized therapy has not been established. Here, we report on a 58 year‐old man with type 1 diabetes mellitus, who developed progressive CA with high levels of serum and cerebrospinal fluid (CSF) anti‐GAD‐Ab. He was initially treated with intravenous high‐dose methylprednisolone and intravenous immunoglobulin (IVIg), but his CA was gradually worsened. Additional combined immunotherapies with plasma exchange, intravenous cyclophosphamide, and rituximab finally stabilized the progressive CA and suppressed the CSF anti‐GAD‐Ab index. Our case suggests the effectiveness of combined immunotherapies against progressive CA and the usefulness of the CSF anti‐GAD‐Ab index as a therapeutic indicator.
Functions of the SNAI family in chondrocyte‐to‐osteocyte development
Authors: Razmara Ehsan , Bitaraf Amirreza , Karimi Behnaz , Babashah Sadegh 
Published: August 2021

AbstractDifferent cellular mechanisms contribute to osteocyte development. And while critical roles for members of the zinc finger protein SNAI family (SNAIs) have been discussed in cancer‐related models, there are few reviews summarizing their importance for chondrocyte‐to‐osteocyte development. To help fill this gap, we review the roles of SNAIs in the development of mature osteocytes from chondrocytes, including the regulation of chondro‐ and osteogenesis through different signaling pathways and in programmed cell death. We also discuss how epigenetic factors—including DNA methylation, histone methylation and acetylation, and noncoding RNAs—contribute differently to both chondrocyte and osteocyte development. To better grasp the important roles of SNAIs in bone development, we also review genotype–phenotype correlations in different animal models. We end with comments about the possible importance of the SNAI family in cartilage/bone development and the potential applications for therapeutic goals.
FOXD1‐AS1 upregulates FOXD1 to promote oral squamous cell carcinoma progression
Authors: Ma Yuxin , Han Jingchao , Luo Xi 
Published: August 2021

AbstractObjectivesRecently, increasing attention has been concentrated on decrypting the potential of long non‐coding RNAs (lncRNAs) in influencing the progression of human tumors, oral squamous cell carcinoma (OSCC) included. The role of a novel lncRNA, forkhead box D1 antisense RNA 1 (FOXD1‐AS1), has been discussed in multiple cancers. Nevertheless, its function and relevant mechanism in OSCC have been not probed yet.Materials and methodsFOXD1‐AS1 expression was detected via RT‐qPCR. Colony formation, EdU, transwell and Western blot analyses tested the functional role of FOXD1‐AS1 in OSCC cells. The relationship between RNAs was assessed by a series of mechanical assays.ResultsFOXD1‐AS1 was expressed at a high level in head and neck squamous cell carcinoma (HNSC). Knockdown of FOXD1‐AS1 exerted repressive impacts on OSCC cell proliferation, migration, invasion, and EMT. Moreover, FOXD1‐AS1 positively regulated its nearby gene FOXD1 via interacting with miR‐369‐3p. In addition, adenosine deaminase RNA specific (ADAR), known as a RNA‐binding protein (RBP), was capable to bind with FOXD1‐AS1 and FOXD1 simultaneously, and could regulate the stability of FOXD1 mRNA. Aside from that, rescue assays delineated that FOXD1‐AS1 promoted OSCC progression via upregulating FOXD1.ConclusionsFOXD1‐AS1 elevates FOXD1 expression to promote OSCC malignant phenotypes through miR‐369‐3p and ADAR.
The Impacts of Temperature Shocks on Birth Weight in Vietnam
Authors: Le Kien , Nguyen My 
Published: August 2021

AbstractThis paper investigates the extent to which in utero exposure to temperature shocks affects birth weight outcomes in Vietnam. Exploiting the variations across districts and conception timing within districts, we show that a one standard deviation increase in temperature relative to the local norm (approximately 0.52°C) during the first trimester of pregnancy reduces the child's weight at birth by 67 g or 2.2 percent. Our heterogeneity analysis suggests that infants living in rural areas, born to poor and low‐educated mothers are especially vulnerable to temperature shocks.
A clock regulatory module is required for salt tolerance and control of heading date in rice
Authors: Wang Xiling , He Yuqing , Wei Hua , Wang Lei 
Published: August 2021

AbstractThe circadian clock plays multiple roles in plant stress responses and developmental transition phases. Nevertheless, the underlying molecular mechanisms and individual clock components that coordinately regulate important agronomic traits of rice such as salt tolerance and heading date remain to be elucidated. Here, we identify a rice ternary repressive protein complex composed of OsELF4a, OsELF3‐1 and OsLUX, which was designated as OsEC1 in analogy to a similar complex in Arabidopsis. OsELF4a physically interacts with OsELF3‐1 and OsELF3‐2 in nucleus, whilst OsELF3‐1 rather than OsELF3‐2 strongly interacts with OsLUX, a Myb‐domain containing transcriptional factor. Phenotypic analyses show a role for this complex in heading and salt tolerance. The loss‐of‐function mutants of OsEC1 exhibit lower survival rate under salt stress and late heading date. Transcriptomic profiling together with biochemical assays identified the GIGANTEA homologue OsGI as a direct transcriptional target of OsEC1. Notably, the osgi‐101 mutant, generated by CRISPR/Cas9, is salt tolerant and exhibits early heading date in long day conditions. Together, our findings characterized a transcriptional module in rice composed by the OsEC1 repressing OsGI, which links the circadian clock with salt tolerance and control of heading date.
Heterologous expression of CYP81A6 from rice (Oryza sativa) in Escherichia coli and structural analyses of bensulfuron‐methyl metabolites
Authors: Yamaguchi Takuya , Matsumura Kohei , Iwakami Satoshi , Sunohara Yukari , Matsumoto Hiroshi 
Published: August 2021

AbstractHerbicides are often selective and kill only weeds without affecting crops. In rice, CYP81A6 is responsible for tolerance toward acetolactate synthase herbicides such as bensulfuron‐methyl (BSM). CYP81A6 is thought to metabolize BSM into a nontoxic metabolite, that is, O‐demethylated BSM. However, direct evidences for this reaction have not been reported, likely due to difficulties in the heterologous expression of plant P450s in bacterial expression systems. In this study, we established CYP81A6 expression in Escherichia coli via modification of its N‐terminal basic region coding sequence, optimization of cultivation temperature, and selection of E. coli strains. Heterologous production of CYP81A6 was evaluated by the conversion of BSM in autoinduction medium after the culture, compared to that with an empty vector control. The optimized heterologous production condition of rice CYP81A6 in E. coli using 48‐well plates involved replacement of the N‐terminal basic region with that of CYP2C3, the use of E. coli BL21(DE3) as an expression host, and culture at 34°C. Further, co‐expression of gene encoding glucose dehydrogenase enhanced the conversion of 0.5 mM BSM from 58.7 to 73.1% in the optimized condition. In the optimization process, we detected two metabolites, M1 and M2. Mass spectrometry and 1H nuclear magnetic resonance analyses indicated that M1 was O‐demethylated BSM. Although we could not isolate M2 because of its low abundance in the medium, mass spectrometry analysis suggested that it was the monooxygenated (+O) form of BSM. Overall, these results confirm that CYP81A6 catalyzes the formation of O‐demethylated BSM from BSM.
Association of deleterious sucking habits with the occurrence of otitis in newborns, infants, preschool children, and children: a systematic review protocol
Authors: Castro-Cunha Ana Claudia , Gonçalves Isabela Costa , Martins-Júnior Paulo Antônio , Fernandes Izabella Barbosa , Abreu Lucas Guimarães , Paiva Saul Martins , Bendo Cristiane Baccin 
Published: August 2021

ABSTRACT

Objective:
The objective of this review is to determine whether deleterious sucking habits contribute to otitis in newborns, infants, preschool children, and children.

Introduction:
Otitis is one of the most prevalent diseases in infants. Diverse studies have suggested that deleterious sucking habits, such as pacifier use, bottle-feeding, and finger-sucking, may be risk factors for the development of otitis in young individuals.

Inclusion criteria:
This systematic review will include observational studies in which the association between deleterious sucking habits and otitis was assessed in newborns, infants, preschool children, and children. Studies will compare caregiver reporting of sucking habits in this population to those with no deleterious sucking habits or those who exclusively breastfeed. The primary outcome will be the presence of otitis.

Methods:
The searches will be carried out in six electronic databases, and gray literature will also be screened. A three-step search strategy will be used, with no date or language restrictions. Studies whose full text meets the eligibility criteria will be included in the systematic review. Study screening and selection, critical appraisal, and data extraction will be performed by two independent reviewers. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the certainty of the evidence. Meta-analysis will be performed if there is relative homogeneity among included studies.

Systematic review registration number:
PROSPERO CRD42020197162
Adverse childhood experiences—household stressors and children’s mental health: a single centre retrospective review
Authors: Holmes Hilary , Darmanthe Nicolas , Tee Kevin , Goodchild Margaret 
Published: August 2021

ObjectiveTo determine the prevalence of reported ‘household stressor’ adverse childhood experiences (ACEs) in families of children presenting with neurodevelopmental, behavioural or emotional difficulties and to determine whether family vulnerabilities, individually or cumulatively, were associated with particular clinical symptomatology.DesignRetrospective chart review followed by statistical analysis of family stressors and clinical symptomatology.SettingA community paediatric clinic in Australia.ParticipantsAll 267 children who attended an initial paediatric appointment during 2018.Results162 (60.7%) children had been exposed to one or more household stressor ACEs, including 116 (43.4%) children exposed to parental mental illness. Behavioural disturbance occurred in 144 (53.9%) children and externalising behaviours (other than attention deficit hyperactivity disorder) were more frequent than internalising behaviours. Externalising and internalising behaviours were associated with individual and cumulative household stressor ACEs. Most other symptomatology apart from genetic/neurological conditions, autistic symptoms and some developmental delays appeared to be partially associated with ACEs.ConclusionHousehold stressor ACEs were common, frequently occurred concurrently, and were associated with much of the symptomatology, in this cohort. Parental mental illness was the most prevalent stressor and behavioural disturbance the most prevalent symptomatology. These findings may have implications for clinical practice and service provision.
Association between time-to-treatment and outcomes in non-small cell lung cancer: a systematic review
Authors: Hall Helen , Tocock Adam , Burdett Sarah , Fisher David , Ricketts William M , Robson John , Round Thomas , Gorolay Sarita , MacArthur Emma , Chung Donna , Janes Sam M , Peake Michael D , Navani Neal 
Published: August 2021

BackgroundNational targets for timely diagnosis and management of a potential cancer are driven in part by the perceived risk of disease progression during avoidable delays. However, it is unclear to what extent time-to-treatment impacts prognosis for patients with non-small cell lung cancer, with previous reviews reporting mixed or apparently paradoxical associations. This systematic review focuses on potential confounders in order to identify particular patient groups which may benefit most from timely delivery of care.MethodsMedline, EMBASE and Cochrane databases were searched for publications between January 2012 and October 2020, correlating timeliness in secondary care pathways to patient outcomes. The protocol is registered with PROSPERO (the International Prospective Register of Systematic Reviews; ID 99239). Prespecified factors (demographics, performance status, histology, stage and treatment) are examined through narrative synthesis.ResultsThirty-seven articles were included. All but two were observational. Timely care was generally associated with a worse prognosis in those with advanced stage disease (6/8 studies) but with better outcomes for patients with early-stage disease treated surgically (9/12 studies). In one study, patients with squamous cell carcinoma referred for stereotactic ablative radiotherapy benefited more from timely care, compared with patients with adenocarcinoma. One randomised controlled trial supported timeliness as being advantageous in those with stage I–IIIA disease.ConclusionThere are limitations to the available evidence, but observed trends suggest timeliness to be of particular importance in surgical candidates. In more advanced disease, survival trends are likely outweighed by symptom burden, performance status or clinical urgency dictating timeliness of treatment.
Dynamical behavior of simplified FitzHugh–Nagumo neural system with time delay driven by Lévy noise
Authors: Qiu Weida , Guo Yongfeng , Yu Xiuxian 
Published: August 2021

In this paper, the dynamical behavior of the FitzHugh–Nagumo (FHN) neural system with time delay driven by Lévy noise is studied from two aspects: the mean first-passage time (MFPT) and the probability density function (PDF) of the first-passage time (FPT). Using the Janicki–Weron algorithm to generate the Lévy noise, and through the order-4 Runge–Kutta algorithm to simulate the FHN system response, the time that the system needs from one stable state to the other one is tracked in the process. Using the MATLAB software to simulate the process above 20,000 times and recording the PFTs, the PDF of the FPT and the MFPT is obtained. Finally, the effects of the Lévy noise and time-delay on the FPT are discussed. It is found that the increase of both time-delay feedback intensity and Lévy noise intensity can promote the transition of the particle from the resting state to the excited state. However, the two parameters produce the opposite effects in the other direction.
Investigation of Pseudo-Ricci Symmetric Spacetimes in Gray’s Subspaces
Authors: Shenawy Sameh , Chand De Uday , Bin Turki Nasser , Alsaeed Suliman , Abdelhameed Syied Abdallah 
Published: August 2021

In the present paper, we focused our attention to study pseudo-Ricci symmetric spacetimes in Gray’s decomposition subspaces. It is proved that

PRS

n

spacetimes are Ricci flat in trivial,

A

, and

B

subspaces, whereas perfect fluid in subspaces

I

,

I
⊕
A

, and

I
⊕
B

, and have zero scalar curvature in subspace

A
⊕
B

. Finally, it is proved that pseudo-Ricci symmetric GRW spacetimes are vacuum, and as a consequence of this result, we address several corollaries.
Updated Methodology for Projecting U.S.- and State-Level Cancer Counts for the Current Calendar Year: Part II: Evaluation of Incidence and Mortality Projection Methods
Authors: Miller Kimberly D. , Siegel Rebecca L. , Liu Benmei , Zhu Li , Zou Joe , Jemal Ahmedin , Feuer Eric J. , Chen Huann-Sheng 
Published: August 2021

Abstract

Background:
The American Cancer Society (ACS) and the NCI collaborate every 5 to 8 years to update the methods for estimating the numbers of new cancer cases and deaths in the current year for the U.S. and individual states. Herein, we compare our current projection methodology with the next generation of statistical models.

Methods:
A validation study was conducted comparing current projection methods (vector autoregression for incidence; Joinpoint regression for mortality) with the Bayes state-space method and novel Joinpoint algorithms. Incidence data from 1996–2010 were projected to 2014 using two inputs: modeled data and observed data with modeled where observed were missing. For mortality, observed data from 1995 to 2009, 1996 to 2010, 1997 to 2011, and 1998 to 2012, each projected 3 years forward to 2012 to 2015. Projection methods were evaluated using the average absolute relative deviation (AARD) between observed counts (2014 for incidence, 2012–2015 for mortality) and estimates for 47 cancer sites nationally and 21 sites by state.

Results:
A novel Joinpoint model provided a good fit for both incidence and mortality, particularly for the most common cancers in the U.S. Notably, the AARD for cancers with cases in 2014 exceeding 49,000 for this model was 3.4%, nearly half that of the current method (6.3%).

Conclusions:
A data-driven Joinpoint algorithm had versatile performance at the national and state levels and will replace the ACS's current methods.

Impact:
This methodology provides estimates of cancer data that are not available for the current year, thus continuing to fill an important gap for advocacy, research, and public health planning.
Characterizing Trends in Cancer Patients' Survival Using the JPSurv Software
Authors: Mariotto Angela B. , Zhang Fanni , Buckman Dennis W. , Miller Daniel , Cho Hyunsoon , Feuer Eric J. 
Published: August 2021

AbstractBackground:Improvements in cancer survival are usually assessed by comparing survival in grouped years of diagnosis. To enhance analyses of survival trends, we present the joinpoint survival model webtool (JPSurv) that analyzes survival data by single year of diagnosis and estimates changes in survival trends and year-over-year trend measures.Methods:We apply JPSurv to relative survival data for individuals diagnosed with female breast cancer, melanoma cancer, non–Hodgkin lymphoma (NHL), and chronic myeloid leukemia (CML) between 1975 and 2015 in the Surveillance, Epidemiology, and End Results Program. We estimate the number and location of joinpoints and the trend measures and provide interpretation.Results:In general, relative survival has substantially improved at least since the mid-1990s for all cancer sites. The largest improvements in 5-year relative survival were observed for distant-stage melanoma after 2009, which increased by almost 3 survival percentage points for each subsequent year of diagnosis, followed by CML in 1995–2010, and NHL in 1995–2003. The modeling also showed that for patients diagnosed with CML after 1995 (compared with before), there was a greater decrease in the probability of dying of the disease in the 4th and 5th years after diagnosis compared with the initial years since diagnosis.Conclusions:The greatest increases in trends for distant melanoma, NHL, and CML coincided with the introduction of novel treatments, demonstrating the value of JPSurv for estimating and interpreting cancer survival trends.Impact:The JPSurv webtool provides a suite of estimates for analyzing trends in cancer survival that complement traditional descriptive survival analyses.