bluuebunny/crossref_metadata_2025_split huggingface dataset:
RUNX1 gene expression in Egyptian acute myeloid leukemia patients: may it have therapeutic implications?
Authors: Said Fadwa , Shafik Roxan E. , Hassan Naglaa M. 
Published: June 2021

Abstract
Background
Acute myeloid leukemia represents the highest percentage of all adult acute leukemia variants. Runt-related transcription factor1 (RUNX1), a transcription factor with a known tumor suppressor function, was recently reported as a tumor promoter in acute myeloid leukemia (AML). We investigated the role of RUNX1 gene expression level in Egyptian AML patients and delineated its clinical significance.

Results
We measured RUNX1 gene expression level using reverse transcription-quantitative polymerase chain reaction and found that the RUNX1 gene expression level was significantly higher than the control group (p < 0.001). Patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations had a higher expression level of RUNX1 (p = 0.023). The male patients expressed a significantly higher level of RUNX1 (p = 0.046).

Conclusions
The RUNX1 gene is highly expressed in Egyptian AML patients. It has a relation to FLT3-ITD, which may give a clue that patients carrying this mutation may benefit from new treatments that target RUNX1 in the future. Further studies on a larger number of patients with different ethnic groups may give a clearer vision of the therapeutic implications of a new molecular target.
Towards a more relational psychiatry: a critical reflection
Authors: Double Duncan B. 
Published: June 2021

SUMMARYCriticism of the biomedical model of psychiatry that regards mental illness as brain disease has been labelled ‘anti-psychiatry’. Critical psychiatry arises out of so-called anti-psychiatry, but has additional roots in transcultural psychiatry, its alliance with psychiatric user/survivor groups, and the methodological critique of the neuroscientific basis of mental health problems and psychiatric treatment effectiveness. It is not opposed to psychiatry as such and argues for a person-centred shift for practice and research. This article discusses how a more truly biopsychosocial model, which critiques the biomedical model to produce a more relational practice, is needed not only for psychiatry but also for medicine in general.
Depression and executive functioning bidirectionally impair one another across 9 years: Evidence from within-person latent change and cross-lagged models
Authors: Zainal Nur Hani , Newman Michelle G. 
Published: June 2021

Abstract

Background
Scar and vulnerability models assert that increased psychopathology may predict subsequent executive functioning (EF) deficits (and vice versa) over protracted timescales, yet most prior work on this topic has been cross-sectional. Thus, we tested the within- and between-person relations between EF, depression, and anxiety.

Methods
Older adult participants (n = 856) were assessed across four waves, approximately 2 years apart. Performance-based EF and caregiver-rated symptom measures were administered. Bivariate latent change score and random-intercept cross-lagged panel models were conducted.

Results
Within persons, random-intercept cross-lagged panel models revealed that prior greater depression forecasted lower subsequent EF, and vice versa (d = −0.292 vs. −0.292). Bivariate dual latent change score models showed that within-person rise in depression predicted EF decreases, and vice versa (d = −0.245 vs. −0.245). No within-person, cross-lagged, EF-anxiety relations emerged. Further, significant negative between-person EF-symptom relations were observed (d = −0.264 to −0.395).

Conclusion
Prospective, within-person findings offer some evidence for developmental scar and vulnerability models.
Mild Idiopathic Infantile Hypercalcemia—Part 2: A Longitudinal Observational Study
Authors: Lenherr-Taube Nina , Furman Michelle , Assor Esther , Elia Yesmino , Collins Carol , Thummel Kenneth , Levine Michael A , Sochett Etienne 
Published: June 2021

Abstract

Context
Idiopathic infantile hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear.

Objective
The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH.

Methods
This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment, and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4 to 6 months.

Results
Median age at initial diagnosis was 4.5 months. Median levels of serum calcium (2.82 mmol/L) and 1,25 (OH)2D (192 pmol/L) were elevated, whereas serum PTH was reduced (10 ng/L). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1.49 mmol/mmol). All patients who were managed with a low-calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25 dihydroxyvitamin D (1,25(OH)2D) and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants.

Conclusion
The clinical presentation of mild IIH is variable, and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.
The Integration of Sex and Gender Considerations Into Biomedical Research: Lessons From International Funding Agencies
Authors: White Jamie , Tannenbaum Cara , Klinge Ineke , Schiebinger Londa , Clayton Janine 
Published: June 2021

Abstract
To improve the outcomes of research and medicine, government-based international research funding agencies have implemented various types of policies and mechanisms with respect to sex as a biological variable and gender as a sociocultural factor. After the 1990s, the US National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR), and the European Commission (EC) began requesting that applicants address sex and gender considerations in grant proposals, and offering resources to help the scientific community integrate sex and gender into biomedical research. Although it is too early to analyze data on the success of all of the policies and mechanisms implemented, here we review the use both of carrots (incentives) and sticks (requirements) developed to motivate researchers and the entire scientific research enterprise to consider sex and gender influences on health and in science. The NIH focused on sex as a biological variable (SABV) aligned with an initiative to enhance reproducibility through rigor and transparency; CIHR instituted a sex- and gender-based analysis (SGBA) policy; and the EC required the integration of the “gender dimension,” which incorporates sex, gender, and intersectional analysis into research and innovation. Other global efforts are briefly summarized. Although we are still learning what works, we share lessons learned to improve the integration of sex and gender considerations into research. In conjunction with refining and expanding the policies of funding agencies and mechanisms, private funders/philanthropic groups, editors of peer-reviewed journals, academic institutions, professional organizations, ethics boards, health care systems, and industry also need to make concerted efforts to integrate sex and gender into research, and we all must bridge across silos to promote systemwide solutions throughout the biomedical enterprise. For example, policies that encourage researchers to disaggregate data by sex and gender, the development of tools to better measure gender effects, or policies similar to SABV and/or SGBA adopted by private funders would accelerate progress. Uptake, accountability for, and a critical appraisal of sex and gender throughout the biomedical enterprise will be crucial to achieving the goal of relevant, reproducible, replicable, and responsible science that will lead to better evidence-based, personalized care for all, but especially for women.
Genetic Characterization of Short Stature Patients With Overlapping Features of Growth Hormone Insensitivity Syndromes
Authors: Andrews Afiya , Maharaj Avinaash , Cottrell Emily , Chatterjee Sumana , Shah Pratik , Denvir Louise , Dumic Katja , Bossowski Artur , Mushtaq Talat , Vukovic Rade , Didi Mohamed , Shaw Nick , Metherell Louise A , Savage Martin O , Storr Helen L 
Published: June 2021

Abstract

Context
Growth hormone insensitivity (GHI) in children is characterized by short stature, functional insulin-like growth factor (IGF)-I deficiency, and normal or elevated serum growth hormone (GH) concentrations. The clinical and genetic etiology of GHI is expanding.

Objective
We undertook genetic characterization of short stature patients referred with suspected GHI and features which overlapped with known GH–IGF-I axis defects.

Methods
Between 2008 and 2020, our center received 149 GHI referrals for genetic testing. Genetic analysis utilized a combination of candidate gene sequencing, whole exome sequencing, array comparative genomic hybridization, and a targeted whole genome short stature gene panel.

Results
Genetic diagnoses were identified in 80/149 subjects (54%) with 45/80 (56%) having known GH–IGF-I axis defects (GHR n = 40, IGFALS n = 4, IGFIR n = 1). The remaining 35/80 (44%) had diagnoses of 3M syndrome (n = 10) (OBSL1 n = 7, CUL7 n = 2, and CCDC8 n = 1), Noonan syndrome (n = 4) (PTPN11 n = 2, SOS1 n = 1, and SOS2 n = 1), Silver–Russell syndrome (n = 2) (loss of methylation on chromosome 11p15 and uniparental disomy for chromosome 7), Class 3-5 copy number variations (n = 10), and disorders not previously associated with GHI (n = 9) (Barth syndrome, autoimmune lymphoproliferative syndrome, microcephalic osteodysplastic primordial dwarfism type II, achondroplasia, glycogen storage disease type IXb, lysinuric protein intolerance, multiminicore disease, macrocephaly, alopecia, cutis laxa, and scoliosis syndrome, and Bloom syndrome).

Conclusion
We report the wide range of diagnoses in 149 patients referred with suspected GHI, which emphasizes the need to recognize GHI as a spectrum of clinical entities in undiagnosed short stature patients. Detailed clinical and genetic assessment may identify a diagnosis and inform clinical management.
Beckett, Atwood, and Postapocalyptic Tragicomedy
Authors: Dudley Jack 
Published: June 2021

Abstract
Ecological catastrophe has challenged the contemporary novel to find forms that convey the scale and affective conditions of life amid looming planetary devastation. While sincere tragedy has been the dominant mode and tone of the novel's approach, recent scholarship has explored the possibilities of the comic, which presents its own limitations and ethical problems. This article argues that Margaret Atwood's Oryx and Crake moves past these limitations of genre and tone through engagements with the more complicated tragicomic sensibility of Samuel Beckett. The tragicomic first offers Atwood a mode that better conveys the complexity of mixed possible fortunes and futures amid ecological catastrophe while it also better evokes the strange, often contradictory affects of life in the Anthropocene. Yet Atwood sees greater promise in Beckett's tragicomedy beyond his mere endurance of unchangeable existential conditions. She instead repurposes the tragicomic for the ecological and political needs of the contemporary to produce “survival laughter,” an attitude that recognizes the tragic conditions of catastrophe but simultaneously uses comedy to protect the psyche from despair in the face of devastation. Unlike Beckett's laughter that merely endures entropic decline, Atwood's survival laughter opens the possibility for dynamic, creative action oriented to the hope of transformation and flourishing, even amid seemingly total loss. Through tragicomic survival laughter, Atwood moves the ecological novel beyond its dominant mode of sincere tragic disaster while also avoiding the pitfalls of pure comedy to instead imagine more integrated and realistic forms of ecological resilience that powerfully combine mitigation and adaptation.
The structural basis of intraflagellar transport at a glance
Authors: Jordan Mareike A. , Pigino Gaia 
Published: June 2021

ABSTRACT
The intraflagellar transport (IFT) system is a remarkable molecular machine used by cells to assemble and maintain the cilium, a long organelle extending from eukaryotic cells that gives rise to motility, sensing and signaling. IFT plays a critical role in building the cilium by shuttling structural components and signaling receptors between the ciliary base and tip. To provide effective transport, IFT-A and IFT-B adaptor protein complexes assemble into highly repetitive polymers, called IFT trains, that are powered by the motors kinesin-2 and IFT-dynein to move bidirectionally along the microtubules. This dynamic system must be precisely regulated to shuttle different cargo proteins between the ciliary tip and base. In this Cell Science at a Glance article and the accompanying poster, we discuss the current structural and mechanistic understanding of IFT trains and how they function as macromolecular machines to assemble the structure of the cilium.
Study on the Formation Process of Oxide Ion and the Influence of Carbon Matrix in Inductively Coupled Plasma Mass Spectrometry Using 18O-Labeled Arsenous Acid
Authors: Ariga Tomoko , Zhu Yanbei , Inagaki Kazumi 
Published: June 2021

Abstract
To obtain further insight into the mechanism of carbon-induced signal enhancement of arsenic (As) at m/z = 75 in inductively coupled plasma mass spectrometry (ICP-MS), the formation process of arsenic oxide ion (AsO+) and the influence of carbon matrix on the process were investigated. The formation process of AsO+ was investigated using arsenous acid isotopically labeled with a highly enriched stable oxygen isotope 18O (H3As18O3). H3As18O3 sample solutions with or without carbon matrix [i.e., 5% (v/v) isopropanol] were analyzed via ICP-MS, and axial intensity profiles of 75As18O+ and 75As16O+ in the ICP were obtained by measuring the signals at axial sampling positions from 3 to 28 mm away from the load coil. Results suggested that AsO+ was formed via two different processes in the ICP: process 1, which involved the decomposition of As-containing molecules (i.e., H3AsO3) to AsO+, and process 2, which involved the recombination between As+ and oxygen originating from liquids introduced into the ICP (e.g., solvents) or gases (e.g., entrained atmospheric gases). In addition, results suggested that carbon matrix has the potential to enhance process 1.
Maternal Moderate-to-Vigorous Physical Activity before and during Pregnancy and Maternal Glucose Tolerance: Does Timing Matter?
Authors: MCDONALD SAMANTHA M. , MAY LINDA E. , HINKLE STEFANIE N. , GRANTZ KATHERINE L. , ZHANG CUILIN 
Published: June 2021

ABSTRACT

Purpose
To assess prospective associations between moderate-to-vigorous physical activity (MVPA) from preconception through pregnancy and glucose metabolism.

Methods
The sample consisted of 2388 women from the NICHD Fetal Growth Studies—Singletons, which enrolled US pregnant women between 8 and 13 wk of gestation. Women recalled their MVPA in periconception (past 12 months, inclusive of first trimester), early-to-mid (13–20 wk of gestation), and mid-to-late second trimester (20–29 wk). These data were obtained at study visits that occurred at enrollment (8–13 wk) and at follow-up visits at 16 to 22 wk and 24 to 29 wk. Moderate-to-vigorous physical activity was recalled using the Pregnancy Physical Activity Questionnaire. Glucose challenge test and oral glucose tolerance test results and gestational diabetes diagnosis (defined by the Carpenter–Coustan criteria) were extracted from medical records. ANCOVA and Poisson regression with robust error variance were performed to estimate associations between MVPA and glucose concentrations and gestational diabetes risk, respectively, controlling for age, race/ethnicity, and prepregnancy body mass index.

Results
Women achieving higher levels of MVPA (≥75th percentile; 760.5 MET·min·wk−1) in early-to-mid second trimester had lower glucose concentrations (β = −3.9 mg·dL−1, 95% CI, −7.4 to −0.5) compared with their least-active counterparts (≤25th percentile; ≤117.0 MET·min·wk−1). Women maintaining recommended levels of MVPA from preconception and first trimester through second trimester (early-to-mid: β = −3.0 mg·dL−1; −5.9 to −0.1; mid-to-late: β = −4.2 mg·dL−1; −8.4 to −0.1) or maintaining sufficient activity throughout second trimester exhibited lower glucose levels (β = −5.6 mg·dL−1; −9.8 to −1.4) compared with their inactive counterparts. No statistically significant associations with gestational diabetes were observed.

Conclusions
These findings demonstrate that achieving MVPA of at least 760.0 MET·min·wk−1 in early-to-mid second trimester or maintaining at least 500 MET·min·wk−1 from preconception through second trimester may be related to improved maternal glucose metabolism in the second trimester.
The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: update of living systematic review
Authors: John Ann , Eyles Emily , Webb Roger T. , Okolie Chukwudi , Schmidt Lena , Arensman Ella , Hawton Keith , O'Connor Rory C. , Kapur Nav , Moran Paul , O'Neill Siobhan , McGuinness Luke A. , Olorisade Babatunde K. , Dekel Dana , Macleod-Hall Catherine , Cheng Hung-Yuan , Higgins Julian P.T. , Gunnell David 
Published: June 2021

Background:The COVID-19 pandemic has caused considerable morbidity, mortality and disruption to people’s lives around the world. There are concerns that rates of suicide and suicidal behaviour may rise during and in its aftermath. Our living systematic review synthesises findings from emerging literature on incidence and prevalence of suicidal behaviour as well as suicide prevention efforts in relation to COVID-19, with this iteration synthesising relevant evidence up to 19thOctober 2020.Method: Automated daily searches feed into a web-based database with screening and data extraction functionalities. Eligibility criteria include incidence/prevalence of suicidal behaviour, exposure-outcome relationships and effects of interventions in relation to the COVID-19 pandemic. Outcomes of interest are suicide, self-harm or attempted suicide and suicidal thoughts. No restrictions are placed on language or study type, except for single-person case reports. We exclude one-off cross-sectional studies without either pre-pandemic measures or comparisons of COVID-19 positive vs. unaffected individuals.Results:Searches identified 6,226 articles. Seventy-eight articles met our inclusion criteria. We identified a further 64 relevant cross-sectional studies that did not meet our revised inclusion criteria. Thirty-four articles were not peer-reviewed (e.g. research letters, pre-prints). All articles were based on observational studies.There was no consistent evidence of a rise in suicide but many studies noted adverse economic effects were evolving. There was evidence of a rise in community distress, fall in hospital presentation for suicidal behaviour and early evidence of an increased frequency of suicidal thoughts in those who had become infected with COVID-19.Conclusions: Research evidence of the impact of COVID-19 on suicidal behaviour is accumulating rapidly. This living review provides a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on suicide risk as the longer term impacts of the pandemic on suicide risk are researched.
Human-centred design of a new microneedle-based hormonal contraceptive delivery system
Authors: Gualeni Benedetta , Hughes Louise , Stauber Isabelle , Ackers Louise , Gorman Angela , Gashuga Dorothy , Dzabala Nettie , Coulman Sion A. , Birchall James C. 
Published: June 2021

Background: It is estimated that 225 million women worldwide have an unmet need for family planning, and more than half live in low- and middle-income countries. Increasing the choice of contraceptive methods available can reduce this unmet need. Microneedle drug delivery systems represent a new technology for minimally invasive self-administration of contraceptives. We explored stakeholders’ views on different aspects of a proposed microneedle-based hormonal contraceptive delivery system. The feedback was used to iteratively develop this delivery system. Methods: Focus group discussions and semi-structured interviews were conducted with potential stakeholders (women and trans males of childbearing age, their partners, and health professionals and organisations that provide family planning advice and contraception services) in Uganda, The Gambia, Malawi, and the UK, exploring concept acceptability and gathering feedback on different aspects of design and usability of the proposed delivery system. Results: Participants viewed the concept of a new, microneedle-based contraceptive favourably. In Uganda, participants were presented with 7 different prototype applicators and identified desirable features of a preferred delivery device; their input reducing the number of prototypes that were subsequently evaluated by stakeholders in The Gambia and the UK. Participants in these countries helped to identify and/or confirm the most desirable characteristics of the applicator, resulting in design consolidation into a refined concept applicator. The final, optimised applicator prototype was validated during user research in Malawi. This human-centred design approach was also used to iteratively develop an information leaflet for the device. During these user studies, other preferred aspects of a contraceptive delivery system were also evaluated, such as anatomical site of application, duration of action, and return to fertility. Conclusions: A new microneedle-based contraceptive delivery system was iteratively developed using a human-centred design approach and was favourably received by potential stakeholders. The product is now being refined for testing in pre-clinical studies.
RNA-Seq analysis of early transcriptional responses to activation in the leukaemic Jurkat E6.1 T cell line
Authors: Felce Suet Ling , Farnie Gillian , Dustin Michael L. , Felce James H. 
Published: June 2021

Background: The leukaemia-derived Jurkat E6.1 cell line has been used as a model T cell in the study of many aspects of T cell biology, most notably activation in response to T cell receptor (TCR) engagement. Methods: We present whole-transcriptome RNA-Sequencing data for Jurkat E6.1 cells in the resting state and two hours post-activation via TCR and CD28. We compare early transcriptional responses in the presence and absence of the chemokines CXCL12 and CCL19, and perform a basic comparison between observed transcriptional responses in Jurkat E6.1 cells and those in primary human T cells using publicly deposited data. Results: Jurkat E6.1 cells have many of the hallmarks of standard T cell transcriptional responses to activation, but lack most of the depth of responses in primary cells. Conclusions: These data indicate that Jurkat E6.1 cells hence represent only a highly simplified model of early T cell transcriptional responses.