bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term spatial tracking of cells affected by environmental insults
Authors: Mohammad Shahid , Page Stephen J. , Sasaki Toru , Ayvazian Nicholas , Rakic Pasko , Kawasawa Yuka Imamura , Hashimoto-Torii Kazue , Torii Masaaki 
Published: December 2020

AbstractBackgroundHarsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny.MethodsThe reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP+and RFP−cortical neurons in animals prenatally exposed to arsenite.ResultsWe detected RFP+neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP+cortical neurons.ConclusionThe reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism.
Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study
Authors: Volk Heather E. , Park Bo , Hollingue Calliope , Jones Karen L. , Ashwood Paul , Windham Gayle C. , Lurman Fred , Alexeeff Stacey E. , Kharrazi Martin , Pearl Michelle , Van de Water Judy , Croen Lisa A. 
Published: December 2020

AbstractBackgroundPerinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy.ObjectivesTo assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study.MethodsEMA is a population-based, nested case–control study which linked archived maternal serum samples collected during weeks 15–19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID;n= 199), ASD with ID (ASD with ID;n= 180), ID without ASD (ID;n= 164), and children from the general population (GP;n= 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit.ResultsPrevious month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from − 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p< 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure.ConclusionThis study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.
DRACP: a novel method for identification of anticancer peptides
Authors: Zhao Tianyi , Hu Yang , Zang Tianyi 
Published: December 2020

AbstractBackgroundMillions of people are suffering from cancers, but accurate early diagnosis and effective treatment are still tough for all doctors. Common ways against cancer include surgical operation, radiotherapy and chemotherapy. However, they are all very harmful for patients. Recently, the anticancer peptides (ACPs) have been discovered to be a potential way to treat cancer. Since ACPs are natural biologics, they are safer than other methods. However, the experimental technology is an expensive way to find ACPs so we purpose a new machine learning method to identify the ACPs.ResultsFirstly, we extracted the feature of ACPs in two aspects: sequence and chemical characteristics of amino acids. For sequence, average 20 amino acids composition was extracted. For chemical characteristics, we classified amino acids into six groups based on the patterns of hydrophobic and hydrophilic residues. Then, deep belief network has been used to encode the features of ACPs. Finally, we purposed Random Relevance Vector Machines to identify the true ACPs. We call this method ‘DRACP’ and tested the performance of it on two independent datasets. Its AUC and AUPR are higher than 0.9 in both datasets.ConclusionWe developed a novel method named ‘DRACP’ and compared it with some traditional methods. The cross-validation results showed its effectiveness in identifying ACPs.
Psychiatry during the Covid-19 pandemic: a survey on mental health departments in Italy
Authors:   The Executive Committee of The Italian Society of Psychiatry, Carpiniello Bernardo , Tusconi Massimo , Zanalda Enrico , Di Sciascio Guido , Di Giannantonio Massimo 
Published: December 2020

Abstract
Background
To date, very few nationwide studies addressing the way in which mental health services are addressing the current pandemics have been published. The present paper reports data obtained from a survey relating to the Italian mental health system conducted during the first phase of the Covid-19 epidemic.

Methods
Two online questionnaires regarding Community Mental Health Centres (CMHC) and General Hospital Psychiatric Wards (GHPW), respectively, were sent to the Heads of all Italian Mental Health Departments (MHDs). Statistical analysis was carried out by means of Chi Square test with Yates correction or the Fisher Exact test, as needed.

Results
Seventy-one (52.9%) of the 134 MHDs and 107 (32.6%) of the 318 GHPWs returned completed questionnaires. Less than 20% of CMHCs were closed and approx. 25% had introduced restricted access hours. A substantial change in the standard mode of operation in CMHCs was reported with only urgent psychiatric interventions, compulsory treatments and consultations for imprisoned people continuing unchanged. All other activities had been reduced to some extent. Remote contacts with users had been set up in about 75% of cases. Cases of COVID positivity were reported for both staff members (approx. 50% of CHMCs) and service users (52% of CHMCs). 20% of CMHCs reported cases of increased aggressiveness or violence among community patients, although only 8.6% relating to severe cases. Significant problems emerged with regard to the availability of personal protective equipment (PPE) for staff members. A reduced number of GHPWs (− 12%), beds (approx.-30%) and admissions were registered (87% of GHPWs). An increase in compulsory admissions and the rate of violence towards self or others among inpatients was reported by 8% of GHPWs. Patient swabs were carried out in 50% of GHPWs. 60% of GHPWs registered the admission to general COVID-19 Units of symptomatic COVID+ non-severe psychiatric patients whilst COVID+ severe psychiatric patients who were non-collaborative were admitted to specifically set up “COVID-19” GHPWs or to isolated areas of the wards purposely adapted for the scope.

Conclusions
The pandemic has led to a drastic reduction in levels of care, which may produce a severe impact on the mental health of the population in relation to the consequences of the expected economic crisis and of the second ongoing wave of the pandemic.
Older persons’ thoughts about death and dying and their experiences of care in end-of-life: a qualitative study
Authors: Tjernberg Johanna , Bökberg Christina 
Published: December 2020

Abstract
Background
Few studies have focused on how older persons living in nursing homes perceive their last period of life. Furthermore, previous research on older persons’ perceptions of death and dying is limited. Hence, there is an urgent need to explore their experiences during their final period in life.

Aim
To explore thoughts about death and dying and experiences of care in end-of-life among older persons living in nursing homes.

Methods
This study employed a qualitative approach including individual interviews with 36 older persons living in Swedish nursing homes. Questions related to quality of life; physical health; thoughts about death, dying, and the future; and experiences related to the living condition and environment were asked. The interview transcripts were analysed through content analysis. The study was approved by the Regional Ethics Review Board (reference number: 2015/4).

Results
The analysis resulted in the identification of three main thematic categories: The unavoidable and unknown end of life, Thoughts on control and Living your last period of life at a nursing home. The older persons did not fear death itself but had some worries about dying. Spending the last stage of life at a nursing home contributed to different thoughts and feelings among the older persons. With a few exceptions, older persons characterized life at the nursing home as boring and felt they were surrounded by people who did not belong there.

Conclusions
This study indicates a need for older persons to talk about death, dying and end-life issues. Furthermore, this study highlighted that the co-residence of cognitively healthy persons and persons with dementia in the same ward adversely affected cognitively healthy persons. This situation resulted in there being not enough time to both handle the care needs of persons with dementia and have the conversations that cognitively healthy persons desired, such as conversations about thoughts about existence, that could have improved their quality of life.

Trial registration
NCT02708498 Date of registration 16 February 2016.
Shaping a data-driven era in dementia care pathway through computational neurology approaches
Authors: Wong-Lin KongFatt , McClean Paula L. , McCombe Niamh , Kaur Daman , Sanchez-Bornot Jose M. , Gillespie Paddy , Todd Stephen , Finn David P. , Joshi Alok , Kane Joseph , McGuinness Bernadette 
Published: December 2020

Abstract
Background
Dementia is caused by a variety of neurodegenerative diseases and is associated with a decline in memory and other cognitive abilities, while inflicting an enormous socioeconomic burden. The complexity of dementia and its associated comorbidities presents immense challenges for dementia research and care, particularly in clinical decision-making.

Main body
Despite the lack of disease-modifying therapies, there is an increasing and urgent need to make timely and accurate clinical decisions in dementia diagnosis and prognosis to allow appropriate care and treatment. However, the dementia care pathway is currently suboptimal. We propose that through computational approaches, understanding of dementia aetiology could be improved, and dementia assessments could be more standardised, objective and efficient. In particular, we suggest that these will involve appropriate data infrastructure, the use of data-driven computational neurology approaches and the development of practical clinical decision support systems. We also discuss the technical, structural, economic, political and policy-making challenges that accompany such implementations.

Conclusion
The data-driven era for dementia research has arrived with the potential to transform the healthcare system, creating a more efficient, transparent and personalised service for dementia.
New insights in the reproducibility of visual and electronic tooth color assessment for dental practice
Authors: Ratzmann Anja , Welk Alexander , Hoppe Stephanie , Fanghaenel Jochen , Schwahn Christian 
Published: December 2020

Abstract
Background
The aim of the study was to compare a 2D and 3D color system concerning a variety of statistical and graphical methods to assess validity and reliability of color measurements, and provide guidance on when to use which system and how to interpret color distance measures, including ΔE and d(0M1).

Methods
The color of teeth 14 to 24 of 35 patients undergoing regular bleaching treatment was visually assessed and electronically measured with the spectrophotometer Shade Inspector™. Tooth color was recorded before bleaching treatment, after 14 days, and again after 6 months. VITAPAN® Classical (2D) and VITA-3D-Master® (3D) served as reference systems.

Results
Concerning repeated measurements, the 2D system was superior to the 3D system, both visually and electronically in terms of ΔE and d(OM1), for statistics of agreement and reliability. All four methods showed strong patterns in Bland-Altman plots. In the 3D system, hue was less reliable than lightness and chroma, which was more pronounced visually than electronically. The smallest detectable color difference varied among the four methods used, and was most favorable in the electronic 2D system. Comparing the methods, the agreement between the 2D and 3D system in terms of ΔE was not good. The reliability of the visual and electronic method was essentially the same in the 2D and 3D systems; this comparability is fair to good.

Clinical relevance
The 3D system may confuse human raters and even electronic devices. The 2D system is the simple and best choice.
Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis
Authors: Casingal Cristine R. , Kikkawa Takako , Inada Hitoshi , Sasaki Yukio , Osumi Noriko 
Published: December 2020

AbstractCorticogenesis is one of the most critical and complicated processes during embryonic brain development. Any slight impairment in corticogenesis could cause neurodevelopmental disorders such as Fragile X syndrome (FXS), of which symptoms contain intellectual disability (ID) and autism spectrum disorder (ASD). Fragile X mental retardation protein (FMRP), an RNA-binding protein responsible for FXS, shows strong expression in neural stem/precursor cells (NPCs) during corticogenesis, although its function during brain development remains largely unknown. In this study, we attempted to identify the FMRP target mRNAs in the cortical primordium using RNA immunoprecipitation sequencing analysis in the mouse embryonic brain. We identified 865 candidate genes as targets of FMRP involving 126 and 118 genes overlapped with ID and ASD-associated genes, respectively. These overlapped genes were enriched with those related to chromatin/chromosome organization and histone modifications, suggesting the involvement of FMRP in epigenetic regulation. We further identified a common set of 17 FMRP “core” target genes involved in neurogenesis/FXS/ID/ASD, containing factors associated with Ras/mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin (mTOR) pathways. We indeed showed overactivation of mTOR signaling via an increase in mTOR phosphorylation in the Fmr1 knockout (Fmr1 KO) neocortex. Our results provide further insight into the critical roles of FMRP in the developing brain, where dysfunction of FMRP may influence the regulation of its mRNA targets affecting signaling pathways and epigenetic modifications.
A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders
Authors: Carbone Elvira Anna , D'Amato Pasquale , Vicchio Giuseppe , De Fazio Pasquale , Segura-Garcia Cristina 
Published: December 2020

Abstract

Background
There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs.

Methods
This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs.

Results
Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation.

Conclusions
Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut–brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.
Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID)
Authors: Crabb Simon J. , Griffiths Gareth , Marwood Ellice , Dunkley Denise , Downs Nichola , Martin Karen , Light Michelle , Northey Josh , Wilding Sam , Whitehead Amy , Shaw Emily , Birtle Alison J. , Bahl Amit , Elliott Tony , Westbury Charlotte , Sundar Santhanam , Robinson Angus , Jagdev Satinder , Kumar Satish , Rooney Claire , Salinas-Souza Carolina , Stephens Christine , Khoo Vincent , Jones Robert J. 
Published: December 2020

PURPOSE Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. PATIENTS AND METHODS ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of docetaxel (75 mg/m2 intravenous, day 1) and prednisolone (5 mg twice daily, oral, day 1-21) and were randomly assigned (1:1) to oral capivasertib (320 mg twice daily, 4 days on/3 days off, from day 2 each cycle), or placebo, until disease progression. Treatment allocation used minimization factors: bone metastases; visceral metastases; investigational site; and prior abiraterone or enzalutamide. The primary objective, by intention to treat, determined if the addition of capivasertib prolonged a composite progression-free survival (cPFS) end point that included prostate-specific antigen progression events. cPFS and overall survival (OS) were also assessed by composite biomarker subgroup for PI3K/AKT/PTEN pathway activation status. RESULTS One hundred and fifty patients were enrolled. Median cPFS was 7.03 (95% CI, 6.28 to 8.25) and 6.70 months (95% CI, 5.52 to 7.36) with capivasertib and placebo respectively (hazard ratio [HR], 0.92; 80% CI, 0.73 to 1.16; one-sided P = .32). Median OS was 31.15 (95% CI, 20.07 to not reached) and 20.27 months (95% CI, 17.51 to 24.18), respectively (HR, 0.54; 95% CI, 0.34 to 0.88; two-sided P = .01). cPFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Grade III-IV adverse events were equivalent between arms (62.2%). The most common adverse events of any grade deemed related to capivasertib were diarrhea, fatigue, nausea, and rash. CONCLUSION The addition of capivasertib to chemotherapy did not extend cPFS in mCRPC irrespective of PI3K/AKT/PTEN pathway activation status. The observed OS result (a secondary end point) will require prospective validation in future studies to address potential for bias.
Nuclear pore complexes in development and tissue homeostasis
Authors: Guglielmi Valeria , Sakuma Stephen , D'Angelo Maximiliano A. 
Published: December 2020

ABSTRACTNuclear pore complexes are multiprotein channels that span the nuclear envelope, which connects the nucleus to the cytoplasm. In addition to their main role in the regulation of nucleocytoplasmic molecule exchange, it has become evident that nuclear pore complexes and their components also have multiple transport-independent functions. In recent years, an increasing number of studies have reported the involvement of nuclear pore complex components in embryogenesis, cell differentiation and tissue-specific processes. Here, we review the findings that highlight the dynamic nature of nuclear pore complexes and their roles in many cell type-specific functions during development and tissue homeostasis.