bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-translational modifications of CDK5 and their biological roles in cancer
Authors: Gao Gui-Bin , Sun Yue , Fang Run-Dong , Wang Ying , Wang Yang , He Qing-Yu 
Published: July 2021

AbstractPost-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.
Spirituality, moral injury and mental health among Chinese health professionals
Authors: Wang Zhizhong , Al Zaben Faten , Koenig Harold G. , Ding Yuanlin 
Published: July 2021

Background
Moral injury has been found to be prevalent among healthcare professionals during the COVID-19 public health crisis.

Aims
The present study examines the relationship between spirituality, moral injury, and mental health among physicians and nurses in mainland China during the COVID-19 pandemic.

Method
An online cross-sectional study was conducted involving 3006 physicians and nurses in mainland China, where the COVID-19 pandemic has caused high rates of hospital admission and death. The Moral Injury Symptoms Scale-Health Professional was administered, along with measures of mental health and spirituality. Hierarchical linear regression modelling was used to examine the mediating and moderating role of moral injury in the relationship between spirituality and mental health.

Results
Spirituality was positively correlated with moral injury (β = 2.41, P < 0.01), depressive symptoms (β = 0.74, P < 0.01) and anxiety symptoms (β = 0.65, P < 0.01) after controlling sociodemographic variables. Moral injury significantly mediated the relationship between spirituality and both depression and anxiety, explaining 60% (0.46/0.76) of the total association between spirituality and depression and 58% (0.38/0.65) of the association with anxiety. No moderating effect of moral injury was found on the spirituality–mental health relationship.

Conclusions
Although they were the findings of a cross-sectional study, these results suggest that concern over transgressing moral values during the pandemic may have been a driving factor for negative mental health symptoms among Chinese health professionals for whom spirituality was somewhat important. Future longitudinal studies are needed to determine the causal nature of these relationships.
Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl
Authors: Andriessen Victoria C , Lightbourne Marissa , Flippo Chelsi , Faucz Fabio R , Delaney Angela , Hannah-Shmouni Fady , Hammond Geoffrey L , Stratakis Constantine A 
Published: July 2021

Abstract
Sex hormone–binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries, and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L (reference range for a girl with a bone age of 10 years, 73 nmol/L [SEM = 10]) [1]. On genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554C&gt;T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.
Role of Liquid–Liquid Separation in Endocrine and Living Cells
Authors: Akiba Kazuhisa , Katoh-Fukui Yuko , Yoshida Kei , Narumi Satoshi , Miyado Mami , Hasegawa Yukihiro , Fukami Maki 
Published: July 2021

AbstractContextRecent studies have revealed that every eukaryotic cell contains several membraneless organelles created via liquid–liquid phase separation (LLPS). LLPS is a physical phenomenon that transiently compartmentalizes the subcellular space and thereby facilitates various biological reactions. LLPS is indispensable for cellular functions; however, dysregulated LLPS has the potential to cause irreversible protein aggregation leading to degenerative disorders. To date, there is no systematic review on the role of LLPS in endocrinology.Evidence acquisitionWe explored previous studies which addressed roles of LLPS in living cells, particularly from the viewpoint of endocrinology. To this end, we screened relevant literature in PubMed published between 2009 and 2021 using LLPS-associated keywords including “membraneless organelle,” “phase transition,” and “intrinsically disordered,” and endocrinological keywords such as “hormone,” “ovary,” “androgen,” and “diabetes.” We also referred to the articles in the reference lists of identified papers.Evidence synthesisBased on 67 articles selected from 449 papers, we provided a concise overview of the current understanding of LLPS in living cells. Then, we summarized recent articles documenting the physiological or pathological roles of LLPS in endocrine cells.ConclusionsThe discovery of LLPS in cells has resulted in a paradigm shift in molecular biology. Recent studies indicate that LLPS contributes to male sex development by providing a functional platform for SOX9 and CBX2 in testicular cells. In addition, dysregulated LLPS has been implicated in aberrant protein aggregation in pancreatic β-cells, leading to type 2 diabetes. Still, we are just beginning to understand the significance of LLPS in endocrine cells.
Health Insurance Loss during COVID-19 May Increase Support for Universal Health Coverage
Authors: Fox Ashley , Choi Yongjin , Lanthorn Heather , Croke Kevin 
Published: July 2021

Abstract
Context: The United States is the only high-income country that relies on employer-sponsored health coverage to insure a majority of its population. Millions of Americans lost employer-sponsored health insurance during the COVID-19–induced economic downturn. We examine public opinion toward universal health coverage policies in this context.
Methods: Through a survey of 1,211 Americans in June 2020, we examine the influence of health insurance loss on support for Medicare for All (M4A) and the Affordable Care Act (ACA) in two ways. First, we examine associations between pandemic-related health insurance loss and M4A support. Second, we experimentally prime some respondents with a vignette of a sympathetic person who lost employer-sponsored coverage during COVID-19.
Findings: We find that directly experiencing recent health insurance loss is strongly associated (10 pp, p &lt; 0.01) with greater M4A support and with more favorable views of extending the ACA (19.3 pp, p &lt; 0.01). Experimental exposure to the vignette increases M4A support by 6 pp (p = 0.05).
Conclusions: In the context of the COVID-19 pandemic, situational framings can induce modest change in support for M4A. However, real-world health insurance losses are associated with larger differences in support for M4A and with greater support for existing safety net policies such as the ACA.
Regional International Organizations and Health: A Framework for Analysis
Authors: Greer Scott L. , Amaya Ana B. , Jarman Holly , Legido-Quigley Helena , McKee Martin 
Published: July 2021

AbstractContext: Regional international organizations (RIOs), from the South African Development Community (SADC) to the European Union (EU), are organizations that promote cooperation among countries in a specific region of the world. Asking what RIOs do to health and health policy by looking only at their formal health policies can understate their effects (e.g., a free trade agreement with no stated health goals can affect health policy) and overstate their effects (as with agreements full of ambition that did not deliver much).Methods: We adopt a “three-faces” framework that identifies RIOs’ direct health policies, the effects of their trade and market policies, and their effects on health via fiscal governance of their member states to better capture their health impact. We tested the usefulness of the framework by examining the Association of Southeast Asian Nations, EU, North American Free Trade Agreement, SADC, and the Union of South American Nations.Findings: All RIOs had some impact on health systems and policies, and, in many cases, the principal policies were not identified as health policy.Conclusions: Such a framework will be useful in understanding the effects of RIOs on health systems and policies because it captures indirect and even unintended health effects in a way that permits development of explanatory theories.
EVI/WLS function is regulated by ubiquitylation and is linked to ER-associated degradation by ERLIN2
Authors: Wolf Lucie M. , Lambert Annika M. , Haenlin Julie , Boutros Michael 
Published: July 2021

ABSTRACT
WNT signalling is important for development in all metazoans and is associated with various human diseases. The ubiquitin–proteasome system (UPS) and regulatory endoplasmic reticulum-associated degradation (ERAD) have been implicated in the production of WNT proteins. Here, we investigated how the WNT secretory factor EVI (also known as WLS) is ubiquitylated, recognised by ERAD components and subsequently removed from the secretory pathway. We performed a focused immunoblot-based RNAi screen for factors that influence EVI/WLS protein stability. We identified the VCP-binding proteins FAF2 and UBXN4 as novel interaction partners of EVI/WLS and showed that ERLIN2 links EVI/WLS to the ubiquitylation machinery. Interestingly, we also found that EVI/WLS is ubiquitylated and degraded in cells irrespective of their level of WNT production. This K11, K48 and K63-linked ubiquitylation is mediated by the E2 ubiquitin-conjugating enzymes UBE2J2, UBE2K and UBE2N, but is independent of the E3 ubiquitin ligases HRD1 (also known as SYVN1) and GP78 (also known as AMFR). Taken together, our study identifies factors that link the UPS to the WNT secretory pathway and provides mechanistic details of the fate of an endogenous substrate of regulatory ERAD in mammalian cells.
This article has an associated First Person interview with the first author of the paper.
A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor
Authors: Jaudon Fanny , Albini Martina , Ferroni Stefano , Benfenati Fabio , Cesca Fabrizia 
Published: July 2021

ABSTRACT
Astroglial cells are key to maintain nervous system homeostasis. Neurotrophins are known for their pleiotropic effects on neuronal physiology but also exert complex functions to glial cells. Here, we investigated (i) the signaling competence of mouse embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF) and, (ii) the role of kinase D-interacting substrate of 220 kDa (Kidins220), a transmembrane scaffold protein that mediates neurotrophin signaling in neurons. We found a shift from a kinase-based response in embryonic cells to a response predominantly relying on intracellular Ca2+ transients [Ca2+]i within postnatal cultures, associated with a decrease in the synthesis of full-length BDNF receptor TrkB, with Kidins220 contributing to the BDNF-activated kinase and [Ca2+]i pathways. Finally, Kidins220 participates in the homeostatic function of astrocytes by controlling the expression of the ATP-sensitive inward rectifier potassium channel 10 (Kir4.1) and the metabolic balance of embryonic astrocytes. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system, and identify Kidins220 as a novel actor in the increasing number of pathologies characterized by astrocytic dysfunctions.
This article has an associated First Person interview with the first authors of the paper.
Dried Blood Spot and Microwave-Induced Combustion in Disposable Vessels: A Successful Combination for Halogen Determination
Authors: Waechter Samuel R , Bizzi Cezar A , Pedrotti Matheus F , Barin Juliano S , Duarte Fabio A 
Published: July 2021

Abstract
A protocol for blood sampling, storage and digestion for subsequent determination of Br, Cl and I by inductively coupled plasma mass spectrometry (ICP-MS) was proposed. The blood sampling was performed by a protocol known as dried blood spot (DBS). Their characteristics make it a perfect couple with microwave-induced combustion in disposable vessels (MIC-DV) for trace elements determination. Strategies for controlling the blood volume or mass collected in the DBS paper were evaluated. Operational conditions of MIC-DV such as the time of vessel purging with O2, suitable absorbing solutions, and blood mass were evaluated. Results for Br, Cl and I determination by ICP-MS after MIC-DV in three venous samples were compared with reference values obtained by analyte determination by ICP-MS and MIC. The limits of quantification achieved combining DBS/MIC-DV/ICP-MS were 0.23 µg g−1 for Br, 66 µg g−1 for Cl, and 27 ng g−1 for I, which were considered fit for purpose. After MIC-DV optimization, a protocol for Br, Cl and I determination in blood was proposed and applied for blood analysis from ten volunteers. The analyte concentration ranged from 1.79 to 3.57 µg g−1 for Br, 2634 to 3113 µg g−1 for Cl and 0.033 to 0.060 µg g−1 for I.
Bias from questionnaire invitation and response in COVID-19 research: an example using ALSPAC
Authors: Fernández-Sanlés Alba , Smith Daniel , Clayton Gemma L , Northstone Kate , Carter Alice R , Millard Louise AC , Borges Maria Carolina , Timpson Nicholas John , Tilling Kate , Griffith Gareth J , Lawlor Deborah A. 
Published: July 2021

Background: Longitudinal studies are crucial for identifying potential risk factors for infection with, and consequences of, COVID-19, but relationships can be biased if they are associated with invitation and response to data collection. We describe factors relating to questionnaire invitation and response in COVID-19 questionnaire data collection in a multigenerational birth cohort (the Avon Longitudinal Study of Parents and Children, ALSPAC). Methods: We analysed online questionnaires completed between the beginning of the pandemic and easing of the first UK lockdown by participants with valid email addresses who had not actively disengaged from the study. We assessed associations of pre-pandemic sociodemographic, behavioural, anthropometric and health-related factors with: i) being sent a questionnaire; ii) returning a questionnaire; and iii) item response (for specific questions). Analyses were conducted in three cohorts: the index children born in the early 1990s (now young adults; 41 variables assessed), their mothers (35 variables) and the mothers’ partners (27 variables). Results: Of 14,849 young adults, 41% were sent a questionnaire, of whom 57% returned one. Item response was >95%. In this cohort, 78% of factors were associated with being sent a questionnaire, 56% with returning one, and, as an example of item response, 20% with keyworker status response. For instance, children from mothers educated to degree-level had greater odds of being sent a questionnaire (OR=5.59; 95% CI=4.87-6.41), returning one (OR=1.60; 95% CI=1.31-1.95), and responding to items (e.g., keyworker status OR=1.65; 95% CI=0.88-3.04), relative to children from mothers with fewer qualifications. Invitation and response rates and associations were similar in all cohorts. Conclusions: These results highlight the importance of considering potential biases due to non-response when using longitudinal studies in COVID-19 research and interpreting results. We recommend researchers report response rates and factors associated with invitation and response in all COVID-19 observational research studies, which can inform sensitivity analyses.
Outstanding records of mammals from two protected areas of central Guerrero, México
Authors: Briseño-Hernández Iván , Naranjo Eduardo J. 
Published: July 2021

Se describen registros notables de 8 especies de mamíferos en categorías de riesgo de acuerdo con la Norma Oficial Mexicana NOM-059, los cuales son nuevos para 2 áreas naturales protegidas de la región centro de Guerrero, México. Estas especies son difíciles de observar y hay pocos estudios, por lo que no se cuenta con registros previos en la zona de estudio. El estudio se realizó entre julio 2018 y julio 2019 con 22 cámaras trampa distribuidas en bosque de pino-encino, bosque de encino-pino, y selva baja caducifolia con un rango de separación entre las mismas de 170 m a 1,300 m. Se compararon los registros fotográficos con registros previos mediante el ingreso de coordenadas a un sistema de información geográfica. Se registró mediante foto-trampeo y observación directa a Herpailurus yagouaroundi, Leopardus pardalis, Leopardus wiedii, Lontra longicaudis, Panthera onca, Coendou mexicanus, Spilogale pygmaea y Tamandua mexicana; estos mamíferos están incluidos como especies en categoría de riesgo de acuerdo con la Norma Oficial Mexicana NOM-059-SEMARNAT-2020. Nuestros resultados son de relevancia para el conocimiento mastozoológico en el estado de Guerrero; antes del presente trabajo no se contaba con información sobre la presencia de estas especies en el área de estudio ni en localidades cercanas. El registro de estas especies sugiere un indicador del buen estado de conservación de la zona estudiada.
Factors associated with patient-reported outcomes following coccygectomy for chronic coccydynia
Authors: Jensen Mads Moss , Milosevic Stefan , Andersen Gustav Østerheden , Carreon Leah , Simony Ane , Rasmussen Mikkel Mylius , Andersen Mikkel Østerheden 
Published: July 2021

Aims The aim of this study was to identify factors associated with poor outcome following coccygectomy on patients with chronic coccydynia and instability of the coccyx. Methods From the Danish National Spine Registry, DaneSpine, 134 consecutive patients were identified from a single centre who had coccygectomy from 2011 to 2019. Patient demographic data and patient-reported outcomes, including pain measured on a visual analogue scale (VAS), Oswestry Disability Index (ODI), EuroQol five-dimension five-level questionnaire, and 36-Item Short-Form Health Survey questionnaire (SF-36) were obtained at baseline and at one-year follow-up. Patient satisfaction was obtained at follow-up. Regression analysis, including age, sex, smoking status, BMI, duration of symptoms, work status, welfare payment, preoperative VAS, ODI, and SF-36 was performed to identify factors associated with dissatisfaction with results at one-year follow-up. Results A minimum of one year follow-up was available in 112 patients (84%). Mean age was 41.9 years (15 to 78) and 97 of the patients were female (87%). Regression showed no statistically significant association between the investigated prognostic factors and a poor outcome following coccygectomy. The satisfied group showed a statistically significant improvement in patient-reported outcomes at one-year follow-up from baseline, whereas the dissatisfied group did not show a significant improvement. Conclusion We did not identify factors associated with poor outcome following coccygectomy. This suggests that neither of the included parameters should be considered contraindications for coccygectomy in patients with chronic coccydynia and instability of the coccyx. Cite this article: Bone Jt Open 2021;2(7):540–544.
Amplitude-modulated continuous-wave laser rangefinder employing
Bessel–Gauss beamforming
Authors: Zhang Chao , Zhang Zheyuan , Liu Sifan , Jin Lei , Sugiura Yohei , Set Sze Yun , Yamashita Shinji , Ito Fumihiko 
Published: July 2021

We propose an amplitude-modulated continuous-wave laser rangefinder
employing Bessel–Gauss beamforming. Our Bessel–Gauss beam was
generated by a newly proposed doublet configuration, which is simple
and low cost. Such a beam was propagated

>

2

m

with a mainlobe having the diameter

<

1

m
m

. We have conducted proof-of-concept
ranging experiments employing the amplitude-modulated continuous-wave
scheme with the Bessel–Gauss beam and obtained ranging results of a
measurement distance up to 2 m. To the best of our knowledge, this is
the first attempt to apply zeroth-order Bessel–Gauss beamforming to
laser rangefinders.
Two-dimensional MoS22H, 1T, and 1T′crystalline phases with incorporated adatoms: theoretical investigation of electronic and optical properties
Authors: Mehmood Faisal , Pachter Ruth , Back Tyson C. , Boeckl John J. , Busch Robert T. , Stevenson Peter R. 
Published: July 2021

Although there has been progress in studying the electronic and optical properties of monolayer and near-monolayer (two-dimensional, 2D)MoS2upon adatom adsorption and intercalation, understanding the underlying atomic-level behavior is lacking, particularly as related to the optical response. Alkali atom intercalation in 2D transition metal dichalcogenides (TMDs) is relevant to chemical exfoliation methods that are expected to enable large scale production. In this work, focusing on prototypical 2DMoS2, the adsorption and intercalation of Li, Na, K, and Ca adatoms were investigated for the 2H, 1T, and 1T′phases of the TMD by the first principles density functional theory in comparison to experimental characterization of 2H and 1T 2DMoS2films. Our electronic structure calculations demonstrate significant charge transfer, influencing work function reductions of 1–1.5 eV. Furthermore, electrical conductivity calculations confirm the semiconducting versus metallic behavior. Calculations of the optical spectra, including excitonic effects using a many-body theoretical approach, indicate enhancement of the optical transmission upon phase change. Encouragingly, this is corroborated, in part, by the experimental measurements for the 2H and 1T phases having semiconducting and metallic behavior, respectively, thus motivating further experimental exploration. Overall, our calculations emphasize the potential impact of synthesis-relevant adatom incorporation in 2DMoS2on the electronic and optical responses that comprise important considerations toward the development of devices such as photodetectors or the miniaturization of electroabsorption modulator components.