bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment with Vitamin D3 in Vitamin D Deficient Adolescents: A Pilot Study
Authors: Kumaratne Mohan , Vigneron Franck , Cisneros Jasmine
Published: December 2020

Multiple epidemiological studies have shown that vitamin D deficiency is highly prevalent amongst adolescents in the USA. However, recommendations regarding the treatment of vitamin D deficiency in healthy adolescents are not well defined. We carried out a prospective pilot study, to determine whether treatment with 2000 international units of vitamin D3 daily for 3 months, would normalize the vitamin D levels in vitamin D deficient adolescents. Following treatment there was a 56.02% increase in the vitamin D levels from the mean baseline values and 80.39% of the subjects normalized their vitamin D levels. There were no adverse effects associated with this intervention. This study offers complementary guidelines to the existing recommendations from the American Academy of Pediatrics on the optimal dose and duration of vitamin D3 therapy in vitamin D deficient, but otherwise healthy adolescents. Further prospective, large scale, case control studies are indicated to validate our results.
COVID-19 and Alternative Care in South Africa: Children’s Responses to the Pandemic. A Case Study from a Child and Youth Care Centre in Mogale City
Authors: Swanzen Rika , Jonker Gert
Published: December 2020

The experiences from a case study are evaluated against the aspects such as emergency response to vulnerable populations and other sources from the literature to serve as guidelines for the management of an epidemic in a child and youth care centre (CYCC). To help understand the effects of the epidemic on the centre, this article describes experiences in terms of the meeting of needs. A discussion of the following are part of the article:

• A reflection will be provided on the observed stages the children and child and youth care workers (CYCWs) went through during 177 days of a national lockdown;

• Indications of caregiver burnout;

• Experiences around the meeting of children’s needs through the lens of child and youth care (CYC) theory; and

• Proposed areas needing attention in mitigating risks.

Some lessons learnt from the daily routine established to manage the lockdown regulations, sometimes experienced as nonsensical, are shared. From these reflections, questions for research are provided from a practice-based evidence approach, mainly aimed at determining the readiness of a CYCC to manage a state of disaster, while needing to focus on meeting children’s needs.
Retaining an age-diverse workforce through HRM: The mediation of work engagement and affective commitment
Authors: Sousa Inês C. , Ramos Sara , Carvalho Helena
Published: December 2020

An aging population and an increasingly age-diverse workforce exemplify the complex challenge that age represents for most managers today. For that reason, research has shown the importance of designing and implementing human resources (HR) practices that meet age-related differences in workers’ motives and needs. Drawing on signaling and social exchange theories, the current study investigated a first stage moderated parallel multiple mediation model. We examined the mediating roles of work engagement and affective commitment in the relationship between age-diversity practices and turnover intention, as well as the moderating role of work centrality in these mediated relationships. Using a sample of 802 Portuguese workers, the study supported the parallel multiple mediation hypotheses. Further, the findings revealed that work centrality moderated the relationship between age-diversity practices and turnover intention via work engagement, but not via affective commitment. Age-diversity practices may motivate those workers who place less importance on work to be more engaged, which, in turn, reduces their intentions to leave the organization. Moreover, all workers, regardless of the importance that work plays in their life, are more emotionally attached to the organization and more willing to stay when there are age-diversity practices. Thus, to retain a healthy and productive age-diverse workforce, organizations should implement age-diversity practices. Empirical and practical implications are discussed.
Everything comes at a price: The influence of job seekers’ motives on preference in the trade-off between pay and leisure
Authors: de Groote Julia K , Grütter Marco , Koch Andri
Published: December 2020

Recruitment research has often neglected behavioral outcomes in the context of job choice acceptance, and insight into the relationship between individual differences and recruitment outcomes remains scarce. The present paper investigates how the need for achievement, the need for power, and the need for affiliation are related to the preference for either higher pay or more leisure, and we model this relationship as a trade-off. We test our hypotheses with data from 605 individuals. To measure job offer acceptance, we develop a new methodology that allows participants to choose between a set of contracts that are customized for each participant based on individual reference points. We find that the need for achievement and the need for power are significantly positively related to the preference for higher pay, which results in less leisure. We do not find a significant direct effect of the need for affiliation. We discuss the implications of the study in relation to the needs-supplies fit perspective and show the practical applicability of our approach to customizing working contracts.
Echocardiographic Prevalence and Risk Predictors of Ventricular Dysfunction in Connective Tissue Disorders: Tertiary Care Hospital-Based Prospective Case-Control Study
Authors: Thakur Saru , Tegta Geeta Ram , Negi Prakash Chand , Mahajan Kunal , Verma Ghanshyam , Gupta Mudita , Negi Ajeet , Sharma Reena , Verma and Kuldeep
Published: December 2020

Background:

There is a paucity of contemporary Indian data about the prevalence of cardiac abnormalities in patients of connective tissue disorders (CTD) and their risk determinants.

Methods:

We prospectively recorded data from 35 consecutive CTD patients who presented to our out-patient department and had no significant cardiovascular risk factors at baseline. We also recorded data from their age- and sex-matched controls. All cases and controls were subjected to 12 lead electrocardiogram and echocardiography after routine investigations.

Results:

The CTD group comprised 19 (54.3%) patients of systemic lupus erythematosus, 12 (34.3%) patients of systemic sclerosis, 2 (5.7%) patients of mixed CTD, and 1 (2.9%) patient each of overlap syndrome and dermatomyositis. Cardiovascular involvement on echocardiography was documented in 71.4% of CTD patients despite majority of them having no cardiac symptom. Overt left ventricular (LV) systolic dysfunction was observed in 3 (8.6%) CTD patients, while subclinical LV systolic dysfunction was recorded in 13 (37.1%) patients. LV diastolic dysfunction was observed in 11.4% (n = 4) patients. RV systolic dysfunction was prevalent in 20% (n = 7) patients. Pulmonary hypertension was observed in 40% (n = 14) of CTD patients.

Conclusion:

The present study evaluated subclinical LV systolic dysfunction and pulmonary hypertension in about one third of CTD patients. It is imperative to screen for these abnormalities in CTD to ensure timely diagnosis and treatment.
Tunnel performance during the Puebla-Mexico 19 September 2017 earthquake
Authors: Mayoral Juan M , Mosqueda Gilberto , De La Rosa Daniel , Alcaraz Mauricio
Published: December 2020

Seismic performance of tunnels during earthquakes in densely populated areas requires assessing complex interactions with existing infrastructure such as bridges, urban overpasses, and metro stations, including low- to medium-rise buildings. This article presents the numerical study of an instrumented tunnel, currently under construction on stiff soils, located in the western part of Mexico City, during the Puebla-Mexico 19 September 2017 earthquake. Three-dimensional finite difference models were developed using the software FLAC3D. Initially, the static response of the tunnel was evaluated accounting for the excavation technique. Then, the seismic performance evaluation of the tunnel was carried out, computing ground deformations and factors of safety, considering soil nonlinearities. Good agreement was observed between predicted and observed damage during post-event site observations. Once the soundness of the numerical model was established, a numerical study was undertaken to investigate the effect of frequency content in tunnel-induced ground motion incoherence for tunnels built in cemented stiff soils. A series of strong ground motions recorded during normal and subduction events were used in the simulations, considering a return period of 250 years, as recommended in the Mexico City building code. From the results, it was concluded that the tunnel presence leads to important frequency content modification in the tunnel surroundings which can affect low- to mid-rise stiff structures located nearby. This important finding must be taken into account when assessing the seismic risk in highly populated urban areas, such as Mexico City.
ATC Mw7.1 Puebla-Morelos earthquake reconnaissance observations: Structural observations and instrumentation
Authors: Lan Yun Jennifer , Stavridis Andreas , Kim Insung , Diaz-Fanas Guillermo , Heintz Jon , Hernández-Bassal Laura , Anzola Esteban , Berkowitz Russell , Hussain Saif , Jalalian Afshar , Garini Evangelia , Ktenidou Olga-Joan , Yousefianmoghadam Seyedsina , Carrion Homero , Valles-Mattox Rodolfo , Dominguez Maldonado Virgilio , Gama Contreras Andres , Almanza Camacho Sergio R , Bojórquez Hernández René F , Ruiz Medina Victor A , Vallejo Martinez Fernando , Vaxevanis Themis , Hortacsu Ayse , Nikolaou Sissy , Gilsanz Ramon
Published: December 2020

After the 2017 Puebla-Morelos earthquake, the Applied Technology Council (ATC) funded a mission to Mexico City to collect structural, geotechnical, seismological, and damage information on concrete structures. The collected data set includes 70 reinforced concrete buildings and contains photos, design drawings, ground motion records, ambient vibration data, and reconnaissance observations, where available. This article presents the most important structural observations and instrumentation findings. The data show that, in buildings with a flexible lateral system, the unreinforced masonry infill walls resisted substantial load and prevented more severe damage to the structural system. Many previously retrofitted buildings failed in locally unreinforced areas, because retrofits did not comprehensively strengthen all weaknesses in the building. Significant damage was also observed in buildings with weak story irregularities and buildings founded on weak soil.
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

Background

Harsh 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.

Methods

The 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.

Results

We 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.

Conclusion

The 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

Background

Perinatal 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.

Objectives

To 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.

Methods

EMA 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.

Results

Previous 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.

Conclusion

This 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

Background

Millions 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.

Results

Firstly, 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.

Conclusion

We 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

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

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.
Publisher Correction: Spontaneous regression of micro-metastases following primary tumor excision: a critical role for primary tumor secretome
Authors: Shaashua Lee , Eckerling Anabel , Israeli Boaz , Yanovich Gali , Rosenne Ella , Fichman-Horn Suzana , Zvi Ido Ben , Sorski Liat , Haldar Rita , Satchi-Fainaro Ronit , Geiger Tamar , Sloan Erica K. , Ben-Eliyahu Shamgar
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

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

Corticogenesis 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

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

Nuclear 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.
The RNA helicase DDX3 induces neural crest by promoting AKT activity
Authors: Perfetto Mark , Xu Xiaolu , Lu Congyu , Shi Yu , Yousaf Natasha , Li Jiejing , Yien Yvette Y. , Wei Shuo
Published: December 2020

Mutations in the RNA helicase DDX3 have emerged as a frequent cause of intellectual disability in humans. Because many patients carrying DDX3 mutations have additional defects in craniofacial structures and other tissues containing neural crest (NC)-derived cells, we hypothesized that DDX3 is also important for NC development. Using Xenopus tropicalis as a model, we show that DDX3 is required for normal NC induction and craniofacial morphogenesis by regulating AKT kinase activity. Depletion of DDX3 decreases AKT activity and AKT-dependent inhibitory phosphorylation of GSK3β, leading to reduced levels of β-catenin and Snai1, two GSK3β substrates that are critical for NC induction. DDX3 function in regulating these downstream signaling events during NC induction is likely mediated by RAC1, a small GTPase whose translation depends on the RNA helicase activity of DDX3. These results suggest an evolutionarily conserved role of DDX3 in NC development by promoting AKT activity, and provide a potential mechanism for the NC-related birth defects displayed by patients harboring mutations in DDX3 and its downstream effectors in this signaling cascade.
CNS macrophages differentially rely on an intronicCsf1renhancer for their development
Authors: Munro David A. D. , Bradford Barry M. , Mariani Samanta A. , Hampton David W. , Vink Chris S. , Chandran Siddharthan , Hume David A. , Pridans Clare , Priller Josef
Published: December 2020

The central nervous system hosts parenchymal macrophages, known as microglia, and non-parenchymal macrophages, collectively termed border-associated macrophages (BAMs). Microglia, but not BAMs, were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). However, it is unknown whether FIRE deficiency also impacts BAM arrival and/or maintenance. Here, we show that macrophages in the ventricular system of the brain, including Kolmer's epiplexus macrophages, are absent in Csf1rΔFIRE/ΔFIRE mice. Stromal choroid plexus BAMs are also considerably reduced. During normal development, we demonstrate that intracerebroventricular macrophages arrive from embryonic day 10.5, and can traverse ventricular walls in embryonic slice cultures. In Csf1rΔFIRE/ΔFIRE embryos, the arrival of both primitive microglia and intracerebroventricular macrophages was eliminated, whereas the arrival of cephalic mesenchyme and stromal choroid plexus BAMs was only partially restricted. Our results provide new insights into the development and regulation of different CNS macrophage populations.
Lysosomal agents inhibit store-operated Ca2+ entry
Authors: Morgan Anthony J. , Galione Antony
Published: December 2020

Pharmacological manipulation of lysosome membrane integrity or ionic movements is a key strategy for probing lysosomal involvement in cellular processes. However, we have found an unexpected inhibition of store-operated Ca2+ entry (SOCE) by these agents. Dipeptides (GPN and LLOMe) that are inducers of lysosomal membrane permeabilization (LMP) uncoupled ER Ca2+-store depletion from SOCE by interfering with Stim1 oligomerization and/or Stim1 activation of Orai. Similarly, the K+/H+ ionophore, nigericin, that rapidly elevates lysosomal pH, also inhibited SOCE in a Stim1-dependent manner. In contrast, other strategies for manipulating lysosomes (bafilomycin A1, lysosomal re-positioning) had no effect upon SOCE. Finally, the effects of GPN on SOCE and Stim1 was reversed by a dynamin inhibitor, dynasore. Our data show that lysosomal agents not only release Ca2+ from stores but also uncouple this release from the normal recruitment of Ca2+ influx.
Breaking Free from Thermodynamic Constraints: Thermal Acclimation and Metabolic Compensation in a freshwater zooplankton species
Authors: Coggins B. L. , Anderson C. E. , Hasan R. , Pearson A. C. , Ekwudo M. N. , Bidwell J. R. , Yampolsky L. Y.
Published: December 2020

Ectothermic organisms’ respiration rates are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna. We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5 °C - 37 °C) in 8 genotypes of Daphnia representing a range of previously reported acute heat tolerances and, in a narrower range of temperatures (10 °C - 35 °C), in Daphnia with different acclimation history (either 10°C or 25°C). We discovered no difference in temperature-specific respiration rates between heat tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in the 25°C-acclimated Daphnia relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than to low temperature, indicating that metabolic compensation at the lower temperatures require slower, possibly structural changes.
Ultraviolet-visible/near infrared spectroscopy and hyperspectral imaging to study the different types of raw cotton
Authors: Al Ktash Mohammad , Hauler Otto , Ostertag Edwin , Brecht Marc
Published: December 2020

Different types of raw cotton were investigated by a commercial ultraviolet-visible/near infrared (UV-Vis/NIR) spectrometer (210–2200 nm) as well as on a home-built setup for NIR hyperspectral imaging (NIR-HSI) in the range 1100–2200 nm. UV-Vis/NIR reflection spectroscopy reveals the dominant role proteins, hydrocarbons and hydroxyl groups play in the structure of cotton. NIR-HSI shows a similar result. Experimentally obtained data in combination with principal component analysis (PCA) provides a general differentiation of different cotton types. For UV-Vis/NIR spectroscopy, the first two principal components (PC) represent 82 % and 78 % of the total data variance for the UV-Vis and NIR regions, respectively. Whereas, for NIR-HSI, due to the large amount of data acquired, two methodologies for data processing were applied in low and high lateral resolution. In the first method, the average of the spectra from one sample was calculated and in the second method the spectra of each pixel were used. Both methods are able to explain ≥90 % of total variance by the first two PCs. The results show that it is possible to distinguish between different cotton types based on a few selected wavelength ranges. The combination of HSI and multivariate data analysis has a strong potential in industrial applications due to its short acquisition time and low-cost development. This study opens a novel possibility for a further development of this technique towards real large-scale processes.
Psychological burden of the COVID-19 pandemic and its associated factors among frontline doctors of Bangladesh: a cross-sectional study
Authors: Barua Lingkan , Zaman Muhammed Shahriar , Omi Fardina Rahman , Faruque Mithila
Published: December 2020

Background: Frontline doctors are the most vulnerable and high-risk population to get the novel coronavirus disease 2019 (COVID-19) infection. Hence, we aimed to evaluate the anxiety, depression, sleep disturbance and fear of COVID-19 among frontline doctors of Bangladesh during the pandemic, and the associated factors for these psychological symptoms.

Methods: In total, 370 frontline doctors who were involved in the treatment of suspected or confirmed COVID-19 patients during the pandemic took part in an online cross-sectional study. Recruitment was completed using convenience sampling and the data were collected after the start of community transmission of COVID-19 in the country. Anxiety and depression, sleep disturbance, and fear of COVID-19 were assessed by the Patient Health Questionnaire-4, two-item version of the Sleep Condition Indicator, and the Fear of Coronavirus-19 scale, respectively. Socio-demographic information, health service-related information, co-morbidity, and smoking history were collected for evaluating risk factors. The proportion of psychological symptoms were presented using descriptive statistics and the associated factors were identified using multinomial logistic regression analysis.

Results: Of the doctors, 36.5% had anxiety, 38.4% had depression, 18.6% had insomnia, and 31.9% had fear of COVID-19. In multinomial logistic regression, inadequate resources in the workplace were found as the single most significant predictor for all psychological outcomes: anxiety and/or depression (severe, OR 3.0, p=0.01; moderate, OR 5.3, p=0.000; mild, OR 2.3, p=0.003), sleep disturbance (moderate, OR 1.9, p=0.02), and fear of COVID-19 (severe, OR 1.9, p=0.03; moderate, OR 1.8, p=0.03).

Conclusions: The study demonstrated a high burden of psychological symptoms among frontline doctors of Bangladesh during the COVID-19 pandemic situation. Inadequate resources are contributing to the poor mental health of Bangladeshi doctors. The supply of sufficient resources in workplaces and mental health counseling may help to mitigate the burden of the psychological symptoms identified among the respondents..
Factors influencing non-adherence to opioids in cancer patients: a mixed-methods cross-sectional study
Authors: Seangrung Rattaphol , Ahuja Mallika , Pasutharnchat Koravee , Mahawan Rungwipha
Published: December 2020

Background: Strong opioids are mainly utilized to attenuate pain in cancer patients. Adherence to analgesic drugs significantly promotes adequate pain management and improves quality of life. We aimed to identify the factors influencing non-adherence to strong opioids in cancer patients.

Methods: A descriptive, cross-sectional, two-phased, mixed methods design was conducted prospectively to evaluate a cohort of 101 cancer patients who are currently prescribed strong opioids from a pain clinic in Thailand between January and March 2018. Participants were asked to complete a questionnaire that included the following sections: general characteristics; the Medication Taking Behavior in Thai (MTB-Thai) for assessing adherence to medications; and factors influencing nonadherence, which were analyzed using multivariate logistic regression. In addition, face-to-face in depth interviews were conducted with patients showing non-adherence to strong opioids (MTB-Thai score ≤21) and analyzed using thematic content analysis. 

Results: Of 101 cancer pain patients that completed the questionnaire, 39.6% showed non-adherence to strong opioids. Illness understanding (P=0.047) and the use of more than three types of pain medication (P=0.032) were significant factors influencing non-adherence. Qualitative analysis indicated that fear of long-term outcomes, opioid side effects, ineffective pain control, attempts to make the regimen more acceptable, poor understanding, and non-acceptance of disease related to non-adherence.

Conclusion: Non-adherence to opioids for cancer patients is a common problem. Awareness of patient factors, medication-related factors, and illness-related factors will provide the knowledge and adequate advice that may enhance adherence to medications.
Analysis of cancer diagnoses from 2015-2019 within Machakos County, Kenya, support establishment of Cancer Centre in 2019 likely changing referral patterns
Authors: Kamita Moses , Mweni Sharon , Nzioka Ancent , Figueroa Jonine D. , Makokha Francis
Published: December 2020

Background: In Kenya, cancer is an increasing public health challenge, with an estimated 48,000 new cancer cases and over 33,000 deaths recorded each year. Machakos County, Kenya, recently opened a cancer centre with an aim of bringing cancer services such as surgical oncology, chemotherapy, radiotherapy, and pathological services closer to the residents of Machakos County. The county is also one of four counties selected for the universal health coverage pilot programme making it uniquely poised to inform cancer control programs at the local, national, and international levels.

Methods: This study aimed to build a cancer database to enable future population-based cancer studies by reviewing cancer diagnosis records for selected major public hospitals in Machakos County from 2015-2019. Medical records data were retrieved from Machakos Level 5 Hospital and Kangundo, Matuu, Kathiani and Mwala Level 4 Hospitals.

Results: A total of 522 cancer cases were recorded across the study period with more than a third (N=172, 33%) diagnosed August-December of 2019 when the Machakos Cancer Centre opened. Among the cancers diagnosed, the majority were in women (59.2%), with cervix uteri (n=106, 34.3%) followed by breast (n=62, 20.1%) as the most common cancers. For males, oesophagus (n=52, 24.4%) followed by prostate (n=43, 20.2%) were the most common cancer types. The highest crude rates per 100,000 persons were for Kangundo 67.4 and Matungulu 53.2 subcounties.

Conclusion: It is clear that access to cancer care treatment will change referral patterns for residents in Machakos County and with the establishment of this database we expect to enable future population-based surveillance of the cancer burden and research studies, to inform cancer control programs.