bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Alzheimer’s genes via brain transcriptome mapping
Authors: Baik Jae Young , Kim Mansu , Bao Jingxuan , Long Qi , Shen Li ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2022

Abstract
Background
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders characterized by progressive decline in cognitive function. Targeted genetic analyses, genome-wide association studies, and imaging genetic analyses have been performed to detect AD risk and protective genes and have successfully identified dozens of AD susceptibility loci. Recently, brain imaging transcriptomics analyses have also been conducted to investigate the relationship between neuroimaging traits and gene expression measures to identify interesting gene-traits associations. These imaging transcriptomic studies typically do not involve the disease outcome in the analysis, and thus the identified brain or transcriptomic markers may not be related or specific to the disease outcome.

Results
We propose an innovative two-stage approach to identify genes whose expression profiles are related to diagnosis phenotype via brain transcriptome mapping. Specifically, we first map the effects of a diagnosis phenotype onto imaging traits across the brain using a linear regression model. Then, the gene-diagnosis association is assessed by spatially correlating the brain transcriptome map with the diagnostic effect map on the brain-wide imaging traits. To demonstrate the promise of our approach, we apply it to the integrative analysis of the brain transcriptome data from the Allen Human Brain Atlas (AHBA) and the amyloid imaging data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Our method identifies 12 genes whose brain-wide transcriptome patterns are highly correlated with six different diagnostic effect maps on the amyloid imaging traits. These 12 genes include four confirmatory findings (i.e., AD genes reported in DisGeNET) and eight novel genes that have not be associated with AD in DisGeNET.

Conclusion
We have proposed a novel disease-related brain transcriptomic mapping method to identify genes whose expression profiles spatially correlated with regional diagnostic effects on a studied brain trait. Our empirical study on the AHBA and ADNI data shows the promise of the approach, and the resulting AD gene discoveries provide valuable information for better understanding biological pathways from transcriptomic signatures to intermediate brain traits and to phenotypic disease outcomes.
The DNA/RNA helicase DHX9 contributes to the transcriptional program of the androgen receptor in prostate cancer
Authors: Chellini Lidia , Pieraccioli Marco , Sette Claudio , Paronetto Maria Paola 
Published: May 2022

Abstract
Background
Prostate cancer (PC) is the most commonly diagnosed male malignancy and an important cause of mortality. Androgen deprivation therapy is the first line treatment but, unfortunately, a large part of patients evolves to a castration-resistant stage, for which no effective cure is currently available. The DNA/RNA helicase DHX9 is emerging as an important regulator of cellular processes that are often deregulated in cancer.

Methods
To investigate whether DHX9 modulates PC cell transcriptome we performed RNA-sequencing analyses upon DHX9 silencing in the androgen-responsive cell line LNCaP. Bioinformatics and functional analyses were carried out to elucidate the mechanism of gene expression regulation by DHX9. Data from The Cancer Genome Atlas were mined to evaluate the potential role of DHX9 in PC.

Results
We found that up-regulation of DHX9 correlates with advanced stage and is associated with poor prognosis of PC patients. High-throughput RNA-sequencing analysis revealed that depletion of DHX9 in androgen-sensitive LNCaP cells affects expression of hundreds of genes, which significantly overlap with known targets of the Androgen Receptor (AR). Notably, AR binds to the DHX9 promoter and induces its expression, while Enzalutamide-mediated inhibition of AR activity represses DHX9 expression. Moreover, DHX9 interacts with AR in LNCaP cells and its depletion significantly reduced the recruitment of AR to the promoter region of target genes and the ability of AR to promote their expression in response to 5α-dihydrotestosterone. Consistently, silencing of DXH9 negatively affected androgen-induced PC cell proliferation and migration.

Conclusions
Collectively, our data uncover a new role of DHX9 in the control of the AR transcriptional program and establish the existence of an oncogenic DHX9/AR axis, which may represent a new druggable target to counteract PC progression.
Machine learning and comparative genomics approaches for the discovery of xylose transporters in yeast
Authors: Fiamenghi Mateus Bernabe , Bueno João Gabriel Ribeiro , Camargo Antônio Pedro , Borelli Guilherme , Carazzolle Marcelo Falsarella , Pereira Gonçalo Amarante Guimarães , dos Santos Leandro Vieira , José Juliana 
Published: May 2022

Abstract
Background
The need to mitigate and substitute the use of fossil fuels as the main energy matrix has led to the study and development of biofuels as an alternative. Second-generation (2G) ethanol arises as one biofuel with great potential, due to not only maintaining food security, but also as a product from economically interesting crops such as energy-cane. One of the main challenges of 2G ethanol is the inefficient uptake of pentose sugars by industrial yeast Saccharomyces cerevisiae, the main organism used for ethanol production. Understanding the main drivers for xylose assimilation and identify novel and efficient transporters is a key step to make the 2G process economically viable.

Results
By implementing a strategy of searching for present motifs that may be responsible for xylose transport and past adaptations of sugar transporters in xylose fermenting species, we obtained a classifying model which was successfully used to select four different candidate transporters for evaluation in the S. cerevisiae hxt-null strain, EBY.VW4000, harbouring the xylose consumption pathway. Yeast cells expressing the transporters SpX, SpH and SpG showed a superior uptake performance in xylose compared to traditional literature control Gxf1.

Conclusions
Modelling xylose transport with the small data available for yeast and bacteria proved a challenge that was overcome through different statistical strategies. Through this strategy, we present four novel xylose transporters which expands the repertoire of candidates targeting yeast genetic engineering for industrial fermentation. The repeated use of the model for characterizing new transporters will be useful both into finding the best candidates for industrial utilization and to increase the model’s predictive capabilities.

Graphical Abstract
Spatial statistical and environmental correlation analyses on vector density, vector infection index and Japanese encephalitis cases at the village and pigsty levels in Liyi County, Shanxi Province, China
Authors: Liu Mei-De , Li Chun-Xiao , Cheng Jing-Xia , Zhao Tong-Yan 
Published: May 2022

Abstract
Background
In the eco-epidemiological context of Japanese encephalitis (JE), geo-environmental features influence the spatial spread of the vector (Culex tritaeniorhynchus, Giles 1901) density, vector infection, and JE cases.

Methods
In Liyi County, Shanxi Province, China, the spatial autocorrelation of mosquito vector density, vector infection indices, and JE cases were investigated at the pigsty and village scales. The map and Enhanced Thematic Mapper (ETM) remote sensing databases on township JE cases and geo-environmental features were combined in a Geographic Information System (GIS), and the connections among these variables were analyzed with regression and spatial analyses.

Results
At the pigsty level, the vector density but not the infection index of the vector was spatially autocorrelated. For the pigsty vector density, the cotton field area was positively related, whereas the road length and the distance between pigsties and gullies were negatively related. In addition, the vector infection index was correlated with the pigsty vector density (PVD) and the number of pigs. At the village level, the vector density, vector infection index, and number of JE cases were not spatially autocorrelated. In the study area, the geo-environmental features, vector density, vector infection index, and JE case number comprised the Geo-Environment-Vector-JE (GEVJ) intercorrelation net system. In this system, pig abundance and cotton area were positive factors influencing the vector density first. Second, the infection index was primarily influenced by the vector density. Lastly, the JE case number was determined by the vector infection index and the wheat area.

Conclusions
This study provided quantitative associations among geo-environmental features, vectors, and the incidence of JE in study sties, one typical northern Chinese JE epidemiological area without rice cultivation. The results highlighted the importance of using a diverse range of environmental management methods to control mosquito disease vectors and provided useful information for improving the control of vector mosquitoes and reducing the incidence of JE in the northern Chinese agricultural context.

Graphical Abstract
Effect of isometric exercise on blood pressure in prehypertensive and hypertensive individuals: protocol for a systematic review and meta-analysis of randomized controlled trials
Authors: de Oliveira Patrícia Caetano , Lehnen Alexandre M. , Waclawovsky Gustavo 
Published: May 2022

Abstract
Background
Systemic arterial hypertension (HTN) is the leading risk factor of cardiovascular disease death. Lifestyle changes are key for the prevention and management of HTN. Regular aerobic exercise training is recommended as part of the management of HTN, and dynamic resistance exercise should be prescribed as an adjuvant to aerobic training. Recent evidence points to the potential benefits of isometric resistance training in reducing blood pressure (BP). Yet, the hypotensive effect of isometric exercise in prehypertensive and hypertensive individuals is not fully understood. Thus, we will examine the effect of isometric exercise in prehypertensive and hypertensive individuals through a systematic review and meta-analysis.

Methods
Our systematic review study will include randomized controlled trials (RCTs) selected from the electronic databases MEDLINE (PubMed), Cochrane, LILACS, EMBASE, Web of Science, and PEDro published in English, Spanish, and Portuguese languages. We will follow the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) and PICOS framework. Our search will involve studies with both male and female participants aged 18 years or more diagnosed with prehypertension or HTN performing one session of isometric exercise (acute effect) or isometric exercise training (chronic effect) compared to a control group (no exercise). We will use the Cochrane Risk of Bias 2 (RoB 2) tool to evaluate the quality of the studies and RStudio software (v1.3.959 for Windows) for statistical analyses.

Discussion
A meta-analysis of a homogeneous sample of prehypertensive and hypertensive individuals involving isometric handgrip exercise alone can further support previous findings and improve our understanding and recommendations for the management of these populations.

Systematic review registration
PROSPERO CRD42020213081.
The importance of N6-methyladenosine modification in tumor immunity and immunotherapy
Authors: Zhang Ze , Liu Furong , Chen Wei , Liao Zhibin , Zhang Wanguang , Zhang Bixiang , Liang Huifang , Chu Liang , Zhang Zhanguo 
Published: May 2022

AbstractAs the most common and abundant RNA modification in eukaryotic cells, N6-methyladenosine (m6A) modification plays an important role in different stages of tumor. m6A can participate in the regulation of tumor immune escape, so as to enhance the monitoring of tumor by the immune system and reduce tumorgenesis. m6A can also affect the tumor progression by regulating the immune cell responses to tumor in tumor microenvironment. In addition, immunotherapy has become the most popular method for the treatment of cancer, in which targets such as immune checkpoints are also closely associated with m6A. This review discusses the roles of N6-methyladenosine modification in tumor immune regulation, their regulatory mechanism, and the prospect of immunotherapy.Graphical Abstract
Adverse childhood experiences among adults with eating disorders: comparison to a nationally representative sample and identification of trauma profiles
Authors: Rienecke Renee D. , Johnson Craig , Le Grange Daniel , Manwaring Jamie , Mehler Philip S. , Duffy Alan , McClanahan Susan , Blalock Dan V. 
Published: May 2022

Abstract
Background
Adverse childhood experiences (ACEs) are prevalent, impact long-term physical and mental health, and are associated with eating disorders (EDs) in adulthood. The primary objectives of the current study were: (1) to examine and compare ACEs between two samples: treatment-seeking adults, and a nationally representative sample of adults, (2) to characterize ACEs items and total scores across demographic and diagnostic information in adults seeking treatment for an ED, (3) to statistically classify ACEs profiles using latent class analysis, and (4) to examine associations between ACEs profiles and diagnosis.

Methods
This cross-sectional study assessed patients with a DSM-5 ED receiving treatment between October 2018 and April 2020 at the inpatient, residential, or partial hospitalization levels of care at one of two private ED treatment facilities. ACEs were assessed with the Adverse Childhood Experiences Survey at admission. Generalized linear models and Welch’s t-tests were used to compare ACEs in the current sample with national estimates. A latent class analysis was conducted to examine subgroups of ACEs responses, and differences in these classes by ED diagnoses were examined with multinomial logistic regression.

Results
Patients with EDs had significantly higher ACEs scores (M = 1.95, SD = 1.90) than the nationally representative sample (M = 1.57, SD = 4.72; t = 6.42, p < .001). Within patients with EDs, four latent classes of ACEs item endorsement were identified. Patients with other specified feeding or eating disorder (OSFED) and binge eating disorder (BED) were more likely to fall into the “Household ACEs” and “Abuse ACEs” groups, respectively, compared to anorexia nervosa—restricting subtype (AN-R).

Conclusions
Patients with EDs reported more ACEs than the nationally representative sample, and differences in total ACEs and latent class membership were found across ED diagnoses. The current study can inform the development of trauma-informed care for patients with EDs.
Enstatite chondrites: condensation and metamorphism under extremely reducing conditions and contributions to the Earth
Authors: Lin Yangting 
Published: May 2022

AbstractEnstatite chondrites are a small clan of meteorites, only ~ 1% out of all meteorite collection. However, they are the most reduced meteorites and have almost identical isotopic compositions to those of the Earth, suggestive of significant contributions to the latter and other terrestrial planets. Enstatite chondrites contain a unique mineral inventory of sulfides of typical lithophile elements, Si-bearing metal, silicide and phosphide, which record the nebular processes and the thermal metamorphism in asteroidal bodies under extremely reducing environments. EH group is mainly characteristic of the higher Si content of metallic Fe–Ni and the higher MnS contents of sulfides than EL group, indicative of a more reducing condition than the latter. However, the fugacity pH2S could be the same in both EH and EL regions, because it was buffered by kamacite and troilite. The majority of sulfides condensed from the nebula, partially enclosing schreibersite micron-spherules formed probably by early melting. Another part of troilite, sphalerite and djerfisherite, intergrown with perryite, were produced via sulfidation of metallic Fe–Ni. Minor exotic components were also found in enstatite chondrites, including Ca-, Al-rich inclusions and FeO-rich silicate clasts. The Ca-, Al-rich inclusions are identical to those in carbonaceous chondrites except for the alteration under reducing environments, and the FeO-rich silicate clasts show reduction reactions, both suggestive of migration of dust in the protoplanetary disk. The highly reducing conditions (as C/O ratios) might be established via repeating evaporation and condensation of water ice and organic matter across the snow line along the protoplanetary disk, but need to find evidence. Another issue is the preservation of submicron-to-micron-sized presolar grains during high-temperature condensation of the major constituent minerals. After accretion, the parent bodies of EH and EL chondrites probably experienced distinct thermal histories, indicated by their distinct petrologic-type distributions and different correlations with the closure temperatures determined by the FeS contents of sulfides in contact with troilite.The composition of (Mg, Mn, Fe)S, a key indicator for condensation and metamorphism of enstatite chondrites.
Curative resection after chemotherapy and chemoradiotherapy for postoperative recurrence of pancreatic tail cancer in the abdominal wall: a case report
Authors: Iio Shunya , Hozaka Yuto , Tanoue Kiyonori , Idichi Tetsuya , Fukuda Kousuke , Nakashima Taiki , Yasudome Ryutaro , Yamasaki Yoichi , Kawasaki Yota , Arigami Takaaki , Nakajo Akihiro , Higashi Michiyo , Mataki Yuko , Kurahara Hiroshi , Ohtsuka Takao 
Published: May 2022

Abstract
Background
Locoregional recurrence and metastasis to the liver, peritoneum, and lung are the most common recurrent patterns of pancreatic ductal adenocarcinoma (PDAC) after radical resection. Recurrence in the abdominal wall is extremely rare. Herein, we report our experience with a patient who had recurrent PDAC in the abdominal wall with long-term survival by means of multidisciplinary therapy.

Case presentation
A 76-year-old Japanese woman was diagnosed with resectable pancreatic tail cancer. She underwent distal pancreatectomy with regional lymphadenectomy after two cycles of gemcitabine plus S-1 as neoadjuvant therapy. She also received eight cycles of S-1 as adjuvant chemotherapy. Approximately 14 months after the initial surgery, imaging examinations identified a mass suggesting recurrence in the abdominal wall at the middle wound that involved the transverse colon. After two cycles of gemcitabine plus nab-paclitaxel, chemoradiotherapy (S-1 plus 45 Gy) and seven cycles of modified FOLFIRINOX (5-fluorouracil/leucovorin, irinotecan, and oxaliplatin) were administered. The patient did not develop any new recurrent lesions during chemotherapy and chemoradiotherapy. Therefore, the recurrent lesion in the abdominal wall and the involved transverse colon were resected. We confirmed the lack of peritoneal dissemination during surgery. Pathological examination revealed that the resected lesion was metastasis of primary PDAC, and the surgical margin was 1 mm. However, re-recurrence localized in the abdominal wall was detected 9 months later. The re-recurrent lesion was diagnosed as local recurrence of the first recurrent lesion. We performed a second resection of the abdominal wall using a femoral myocutaneous flap to achieve sufficient surgical margin. The pathological findings of the resected specimen were the same as those of the previous specimens, and the resection margin was negative. The patient’s postoperative course was uneventful. Seven years after the initial surgery and 3 years and 7 months after the third surgery, the patient is alive with no signs of recurrence.

Conclusions
Long-term survival could be achieved by radical resection with sufficient surgical margins for recurrence of PDAC in the abdominal wall if new other recurrent lesions, including peritoneal dissemination, are prevented through chemotherapy.
The impact of COVID-19 pandemic on sleep quality in healthcare workers in Turkey
Authors: Erdoğan Ayşegül , Berktaş Deniz Tuncel , Öksüz Ali Nuri , Şahin Ahmet Rıza , Koçyiğit Burhan Fatih 
Published: May 2022

Abstract
Background
The COVID-19 pandemic has caused serious concerns and psychological distress globally. Healthcare workers remain one of the most affected groups due to life threatening risks in addition to increased working hours and labor intensity. All these factors may affect sleep quality of this population. The aim of this study is to evaluate the sleep behaviors of healthcare professionals working in secondary and tertiary hospitals in a large population in Turkey and to show how sleep quality is affected during the pandemic process using the easily applicable Jenkins Sleep Scale (JSS). The population of this cross-sectional descriptive study consists of two pandemic hospitals determined in Kahramanmaraş province. In our questionnaire, we asked subjective sleep quality, sleep time, time to fall asleep, total sleep time, and medication use. We also used JSS Turkish version (JSS-TR) to assess sleep quality and the Epworth Sleepiness Scale (ESS) for increased daytime sleepiness.

Results
Healthcare workers who participated in our survey reported that they started to go to bed later, fell asleep later (mean: 41.75 ± 35.35 min), their total sleep time (mean: 6.67 ± 1.88 h) was shortened, and they needed medication to sleep more (5.7%) after the COVID-19 pandemic. During the COVID-19 pandemic, bedtime behavior after 24:00 decreased from 80.1 to 43.9% of those who previously went to bed before 24:00. For those who went to bed after 24:00 before, it increased from 19.9 to 56.1%. In addition, sleep quality as assessed by subjective and JSS significantly deteriorated after the COVID-19 pandemic. Excessive daytime sleepiness increased. Those with ESS > 10 before and after COVID-19 were 3.9% and 14.1%, respectively (p < 0.001).

Conclusions
The COVID-19 pandemic has significantly adversely affected the sleep behavior and sleep quality of healthcare professionals. The JSS is an easily applicable scale for assessing sleep quality in large population studies.
Role of engrailed homeobox 2 (EN2) gene in the development of the cerebellum and effects of its altered and ectopic expressions
Authors: Poudel Phanindra Prasad , Bhattarai Chacchu , Ghosh Arnab , Kalthur Sneha Guruprasad 
Published: May 2022

Abstract
Background
Morphological organization, folial pattern formation and establishment of the neural circuitry within the cerebellum are the important events taking place during the development of the cerebellum. Expression of engrailed homeobox 2 (EN2) gene plays an essential role in taking place of these events in the developing cerebellum.

Main body
A search was performed by following the PRISMA guidelines to review the role of the EN2 gene in the development of the cerebellum. Human and animal in vivo and in vitro studies showed that expression of the EN2 gene maintains the normal development of the cerebellum, morphological organization, cerebellar foliation, fissure formation, establishment of the afferent topography, molecular pattern formation and patterned gene expression in the developing cerebellum. Altered expression of the EN2 gene changes the morphology and folial pattern of the cerebellum, whereas its activation rescues these defects. EN2 gene polymorphism is reported as a susceptible cause for autism spectrum disorder (ASD). Ectopic expression of EN2 gene may result cancer and it also may play anti-oncogenic role depending on the organ of its expression.

Conclusion
Expression of the EN2 gene is essential for the normal development of the cerebellum. Its altered expression results deformed cerebellum, polymorphysm is associated with autism and ectopic expression may results cancer.