bluuebunny/crossref_metadata_2025 huggingface dataset:
A 646C > G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy—data from an observational study
Authors: Zawiejska Agnieszka , Bogacz Anna , Iciek Rafał , Lewicka-Rabska Agnieszka , Brązert Maciej , Mikołajczak Przemysław , Brązert Jacek
Published: October 2021

Aim

Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP.

Method

The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189).

Results

A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014.

Conclusions

The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.
Normal form of equivariant maps in infinite dimensions
Authors: Diez Tobias , Rudolph Gerd
Published: October 2021

Local normal form theorems for smooth equivariant maps between infinite-dimensional manifolds are established. These normal form results are new even in finite dimensions. The proof is inspired by the Lyapunov–Schmidt reduction for dynamical systems and by the Kuranishi method for moduli spaces. It uses a slice theorem for Fréchet manifolds as the main technical tool. As a consequence, the abstract moduli space obtained by factorizing a level set of the equivariant map with respect to the group action carries the structure of a Kuranishi space, i.e., such moduli spaces are locally modeled on the quotient by a compact group of the zero set of a smooth map. The general results are applied to the moduli space of anti-self-dual instantons, the Seiberg–Witten moduli space and the moduli space of pseudoholomorphic curves.
Large Deviations for Subcritical Bootstrap Percolation on the Erdős–Rényi Graph
Authors: Angel Omer , Kolesnik Brett
Published: October 2021

We study atypical behavior in bootstrap percolation on the Erdős–Rényi random graph. Initially a setSis infected. Other vertices are infected once at leastrof their neighbors become infected. Janson et al. (Ann Appl Probab 22(5):1989–2047, 2012) locates the critical size ofS, above which it is likely that the infection will spread almost everywhere. Below this threshold, a central limit theorem is proved for the size of the eventually infected set. In this work, we calculate the rate function for the event that a small setSeventually infects an unexpected number of vertices, and identify the least-cost trajectory realizing such a large deviation.
How Good is the Science That Informs Government Policy? A Lesson From the U.K.’s Response to 2020 CoV-2 Outbreak
Authors: Cooper Jessica , Dimitriou Neofytos , Arandjelovíc Ognjen
Published: October 2021

In an era when public faith in politicians is dwindling, yet trust in scientists remains relatively high, governments are increasingly emphasizing the role of science based policy-making in response to challenges such as climate change and global pandemics. In this paper we question the quality of some scientific advice given to governments and the robustness and transparency of the entire framework which envelopes such advice, all of which raise serious ethical concerns. In particular we focus on the so-called Imperial Model which heavily influenced the government of the United Kingdom in devising its response to the COVID-19 crisis. We focus on and highlight several fundamental methodological flaws of the model, raise concerns as to the robustness of the system which permitted these to remain unchallenged, and discuss the relevant ethical consequences.
Effects of a 16-week multimodal exercise program on activities of daily living in institutionalized individuals with dementia
Authors: Bezold Jelena , Trautwein Sandra , Barisch-Fritz Bettina , Scharpf Andrea , Krell-Roesch Janina , Nigg Claudio R. , Woll Alexander
Published: October 2021

We aimed to examine the effects of a 16-week multimodal exercise program (MEP) on activities of daily living (ADL) in individuals with dementia (IWD). Furthermore, we investigated the participants’ individual response to the MEP and whether baseline cognitive and motor performance explain ADL performance. We conducted a multicenter randomized controlled trial (RCT) involving 319 participants aged ≥ 65 years with mild to moderate dementia. ADL were assessed at baseline and after the 16-week intervention using the Barthel Index (BI), the Erlangen Test of Activities of Daily Living (E-ADL) and the 7‑item Physical Performance Test (PPT-7). We additionally assessed cognitive and motor performance using standardized and validated assessments. Intervention effects were examined through two-factor analysis of variance with repeated measurements applying a per protocol and an intention-to-treat analysis. We compared baseline cognitive and motor performance between positive-responders (positive-R), non-responders (non-R), and negative-responders (negative-R) and examined cognitive and motor performance as potential cofounders of ADL by conducting multiple regression analyses. There were no significant time×group effects on ADL. Between 20 and 32% of participants responded positively to the intervention, i.e., improved ADL performance from baseline to follow-up. Positive-R had worse baseline motor performance compared to non-R. Cognitive and motor performance explained up to 51.4% of variance in ADL. The MEP had no significant overall effect on ADL in IWD. This may be related to insufficient exercise intensity. However, our results indicate that the response to the MEP depends on individual prerequisites which should thus be considered in further research on individual exercise approaches.
Oxygen (O2) reduction reaction on Ba-doped LaMnO3 cathodes in solid oxide fuel cells: a density functional theory study
Authors: Aniagyei Albert , Kwawu Caroline , Kwakye Ralph , Antwi Boniface Yeboah , Osei-Owusu Jonathan
Published: October 2021

The oxygen adsorption and subsequent reduction on the {100} and {110} surfaces of 25% Ba-doped LaMnO3(LBM25) have been studied at the density functional theory (DFT) with Hubbard correction and the results compared with adsorption on 25% Ca-doped LaMnO3(LCM25) and Sr-doped LaMnO3(LSM25). The trend in the reduction energies at the Mn cation sites are predicted to be in the order LSM25 < LBM25 < LCM25. In addition, the trend in dissociation energies for the most exothermic dissociated precursors follow the order LBM25 < LSM25 < LCM25. The adsorption energies (− 2.14 to − 2.41 eV) calculated for the molecular O2precursors at the Mn cation sites of LCM25, LSM25 and LBM25 are thermodynamically stable, when compared directly with the adsorption energies (Eads = − 0.56 to − 1.67 eV) reported for the stable molecular O2precursors on the Pt, Ni, Pd, Cu and Ir {111} surfaces. The predicted Gibbs energies as a function of temperature (T = 500–1100 °C) and pressures (p = 0.2 atm) for the adsorption and dissociation on the surfaces were negative, an indication of the feasibility of oxygen reduction reaction on the {100} and {110} surfaces at typical operating temperatures reported in this work.
Dual-task performance in old adults: cognitive, functional, psychosocial and socio-demographic variables
Authors: Campos-Magdaleno María , Pereiro Arturo , Navarro-Pardo Esperanza , Juncos-Rabadán Onésimo , Facal David
Published: October 2021

Background

Dual tasking, or the ability to executing two tasks simultaneously, has been used in recent research to predict cognitive impairments, physical frailty, and has been linked with cognitive frailty in old adults.

Aim

This study aimed to determine age-related variables can predict dual-task (DT) performance in the older population.

Methods

A total of 258 healthy community-dwelling participants + 60 years were assessed in relation to their functional capacity, health, well-being, social support and years of education. Performance of a cognitive (Fluency) task and a cognitive–motor (Tracking) task was recorded under single and DT conditions. Multiple linear regression analysis was carried out for each dependent variable, in separate models including cognitive, functional and psychosocial variables.

Results

Performance in Fluency in DT conditions was predicted by cognitive variables, whereas performance in Tracking DT conditions was predicted by positive interaction, health status, age and motor variables.

Discussion

The findings suggest that a wide range of cognitive, psychological, social, physical and functional variables influence cognitive and motor performance in aging.

Conclusion

DT methodology is sensitive to different age-related changes and could be related to frailty conditions in aging.
The interplay of familial warmth and LGBTQ+ specific family rejection on LGBTQ+ adolescents’ self‐esteem
Authors: Meanley Steven , Flores Dalmacio D. , Listerud Louis , Chang Cindy J. , Feinstein Brian A. , Watson Ryan J.
Published: October 2021

Introduction

Our study sought to assess the interplay of family dynamics, namely familial warmth and LGBTQ+ specific rejection, and its association to self‐esteem in a non‐probabilistic sample of LGBTQ+ adolescents in the United States.

Methods

Stratified by (1) cisgender and (2) transgender and non‐binary LGBTQ+ adolescents (N = 8774), we tested multivariable regression analyses to assess the association between familial warmth and LGBTQ+ specific family rejection, adjusted for sociodemographic characteristics. We then conducted a sub‐analysis with LGBTQ+ adolescents who reported being out to any family member about their LGBTQ+ identity; specifically, we tested a series of multivariable regression models to assess whether levels of LGBTQ+ specific family rejection attenuated the association between familial warmth and self‐esteem.

Results

Full sample models indicated a positive association between familial warmth and self‐esteem. Findings from our sub‐analysis indicated that familial warmth remained positively linked to self‐esteem and family rejection was negatively associated with self‐esteem. Family rejection was a statistically significant moderator, attenuating the association between familial warmth and self‐esteem. With respect to being out about one's sexual orientation, these findings were robust across gender stratification groups.

Conclusions

Families of origin serve as sources of stress and resilience for LGBTQ+ adolescents. Our findings contribute support to arguments that familial warmth and LGBTQ+ specific rejection are not mutually‐exclusive experiences among LGBTQ+ adolescents. We provide recommendations for multilevel interventions to leverage activities that support positive family dynamics and self‐esteem among LGBTQ+ adolescents.
Machine Learning with Neural Networks
Authors: Mehlig Bernhard
Published: October 2021

This modern and self-contained book offers a clear and accessible introduction to the important topic of machine learning with neural networks. In addition to describing the mathematical principles of the topic, and its historical evolution, strong connections are drawn with underlying methods from statistical physics and current applications within science and engineering. Closely based around a well-established undergraduate course, this pedagogical text provides a solid understanding of the key aspects of modern machine learning with artificial neural networks, for students in physics, mathematics, and engineering. Numerous exercises expand and reinforce key concepts within the book and allow students to hone their programming skills. Frequent references to current research develop a detailed perspective on the state-of-the-art in machine learning research.
Scientific Writing and Publishing
Authors: Wheatley Denys
Published: October 2021

Knowing how to prepare, write and publish high-quality research papers can be challenging for scientists at all stages of their career. This manual guides readers through successfully framing and presenting research findings, as well as the processes involved in publishing in learned journals. It draws on the author's wealth of practical experience, from working in academic research for over 40 years and teaching scientific writing in over 20 countries, to gaining insights as a journal editor. Well-written and logical, it provides clear step-by-step instructions to enable readers to become more effective at writing articles, and navigating difficulties related to journal submission, the review process, editing and publication. It comprehensively covers themes such as publication ethics, along with current topics including Open Access publishing and pre-print servers. This is a useful, user-friendly guide for graduate students, early career scientists, and more experienced researchers, particularly in the life and medical sciences.
Emergency preparedness: What is the future?
Authors: Herstein Jocelyn J. , Schwedhelm Michelle M. , Vasa Angela , Biddinger Paul D. , Hewlett Angela L.
Published: October 2021

Emergency preparedness programs have evolved over the last several decades as communities have responded to natural, intentional, and accidental disasters. This evolution has resulted in a comprehensive all-hazards approach centered around 4 fundamental phases spanning the entire disaster life cycle: mitigation, preparedness, response, and recovery. Increasing frequency of outbreaks and epidemics of emerging and reemerging infectious diseases in the last decade has emphasized the significance of healthcare emergency preparedness programs, but the coronavirus disease 2019 (COVID-19) pandemic has tested healthcare facilities’ emergency plans and exposed vulnerabilities in healthcare emergency preparedness on a scale unexperienced in recent history. We review the 4 phases of emergency management and explore the lessons to be learned from recent events in enhancing health systems capabilities and capacities to mitigate, prepare for, respond to, and recover from biological threats or events, whether it be a pandemic or a single case of an unknown infectious disease. A recurring cycle of assessing, planning, training, exercising, and revising is vital to maintaining healthcare system preparedness, even in absence of an immediate, high probability threat. Healthcare epidemiologists and infection preventionists must play a pivotal role in incorporating lessons learned from the pandemic into emergency preparedness programs and building more robust preparedness plans.
Tacit Knowing: What it is and Why it Matters
Authors: Malik Abida
Published: October 2021

Tacit knowing as a concept and legitimate topic of scholarship came up in philosophical research in the second half of the 20th century in the form of some influential works by Michael Polanyi (although similar concepts had been discussed before). Systematic epistemological studies on the topic are still scarce, however. In this article, I support the thesis that tacit knowing pervades all our common major divisions of knowledge and that it therefore must not be neglected in epistemological research. By this approach I am simultaneously giving a systematic back-up for Polanyi's claim that the tacit component is found in all knowledge.
Evaluation of health-related knowledge, attitudes, and behaviors of undergraduate students by cardiovascular risk factors
Authors: Aydin Volkan , Vizdiklar Caner , Akici Ahmet , Akman Mehmet , Gogas Yavuz Dilek , Altikardes Zehra Aysun , Kucukguzel S. Guniz , Topcu Mumine , Aysevinc Berrin , Fak Ali Serdar
Published: October 2021

Aim:

To determine the presence of cardiovascular (CV) risk (CVR) factors in university students and evaluate how these factors are affected from the knowledge, attitudes, and habits of the individuals regarding healthy lifestyle.

Background:

Starting from early ages, lifestyle habits such as lack of physical activity, unhealthy eating, and inappropriate drug use increase CV and metabolic risks of individuals.

Methods:

In April–May 2018, sociodemographic characteristics of 770 undergraduate students, in addition to their knowledge, attitudes, and habits regarding their nutrition and physical activity status were obtained through face-to-face questionnaires. CVR factors were determined according to blood pressure, blood glucose, total cholesterol levels, and anthropometric measurements. Collected data were compared by CVR factor presence (CV[+] or CV[−]) in students.

Findings:

The mean age of the participants was 22.3 ± 2.6 years. 59.6% were female and 71.5% were students of non-health sciences. In total, 274 individuals (35.9%) belonged to CV(+) group (mean risk number: 1.3 ± 0.5) with higher frequency in males (42.1% versus 31.6%, P < 0.05). The most common CVR factors were smoking (20.6%), high total cholesterol (7.5%), and hypertension/high blood pressure (6.0%). 15.5% of the participants regularly used at least one drug/non-pharmaceutical product. 11.3% complied the Mediterranean diet well. 21.9% of CV(+) stated consuming fast food at lunch compared to 14.3% of CV(−) (P < 0.05). 44.6% stated exercising below the CV-protective level.

Conclusions:

This study showed one-third of university students was at CVR, independent of their sociodemographic characteristics. Furthermore, the students appear to perform below expectations in terms of nutrition and physical activity. Extensive additional measures are needed to encourage young individuals for healthy nutritional and physical activity habits.
The Relationship Between Upward Propagating Atmospheric Gravity Waves and Ionospheric Irregularities During Solar Minimum Periods
Authors: Seba Ephrem B. , Nigussie Melessew , Giday Nigussie M. , Moldwin Mark B.
Published: October 2021

We present a study on the relationship between upward propagating gravity waves and ionospheric irregularities. Gravity waves (GWs) are identified from Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite temperature measurements and nighttime ionospheric irregularities are observed from the three Swarm satellites. Using these two independent set of measurements, we investigate the relationship between gravity waves and ionospheric irregularities on both equinox and solstice seasons for the years 2018–2019. The results show, post‐sunset gravity wave characteristics are important in understanding the variability of global nighttime equatorial plasma density irregularities. We also find out that the pre‐midnight and post‐midnight characteristics of ionospheric irregularities show global westward shift in the occurrence of ionospheric irregularities. Upward propagating gravity waves also show three dominant peaks longitudinally with the strongest being between American and African longitudinal sectors. Strongest gravity wave amplitudes are associated with strongest plasma irregularities. GW suppression is observed around equatorial regions at stratopause region in our measurements which are commonly observed at polar and higher latitudinal regions in many studies. We also observe that, ionospheric irregularities are strongest when GWs are relatively less suppressed.
Advancing Process Representation in Hydrological Models: Integrating New Concepts, Knowledge, and Data
Authors: Guse Björn , Fatichi Simone , Gharari Shervan , Melsen Lieke A.
Published: October 2021

Model fidelity and accuracy in process representations have been the crux of scientific hydrological modeling, creating a pressing need for a better linkage between the development of hydrological models and the growing number of data sources and measurement techniques. Improved representation of process dynamics in hydrological models can provide new insights into complex hydrological systems and point out less understood natural phenomena that need further investigation. This special issue includes contributions that offer potential solutions and strategies to improve and test the representation of hydrological processes. We have organized the special issue contributions into four topical categories: (a) Beyond streamflow, which looks into the power of complementary data sources in addition to traditionally used streamflow for process inference. (b) Challenge of subsurface hydrology, that reflects on lesser understood processes under the surface and their impact on the model structure. (c) Evaporation in hydrological modeling, linking ecological aspects to the hydrological functioning of the natural system. Finally, (d) top down vs. bottom up modeling approaches, relied upon for process representation analysis. The special issue and our reflection on the contributions present a snapshot of ongoing efforts for integrating new concepts, knowledge, and data in process representation in hydrological models.
Interdisciplinary Symptom Management in Pediatric Palliative Care: A Case Report
Authors: Kentor Rachel A. , Krinock Pamela , Placencia Jennifer , Cousins Danielle , Hellsten Melody
Published: October 2021

Objective: Pediatric palliative care (PPC) services strive to prevent and relieve suffering among children, adolescents, and young adults with chronic and/or life-limiting illnesses. The current case report aims to illustrate the methods and effectiveness of an interdisciplinary palliative care team in symptom management of a 19-year-old Mexican American female with complex medical and psychosocial needs, including a history of labor trafficking. The patient, in leukemic remission at time of admission, required close collaboration of subspecialties including Psychology, Pediatric Advanced Care Team, Pain Team, Spiritual Care, and Rehabilitation to comprehensively address total pain. Method: Data were retrospectively extracted from the patient’s medical chart, including numerical pain ratings across time, relative hours of monthly service provision by interdisciplinary specialty, and timeline of medical interventions. Results: Results demonstrated a decrease in patient pain scores over time despite progression of physical deterioration and disability. Characterization of service provision revealed flexibility within and across subspecialties as the patient’s condition evolved. One year following discharge, the patient was reevaluated by Psychology and demonstrated remarkable physical rehabilitation gains as well as resolution of mood and anxiety concerns (evidenced by subclinical scores on the PHQ-9 and GAD-7). Conclusion: Results demonstrate the effectiveness of psychological, spiritual, and palliative care efforts in tandem with tailored medical intervention to address “total pain” and improve patient outcomes. Influences of cultural practices and spiritual beliefs on pediatric palliative care are highlighted throughout. The relative variance of service provision within and across time points illustrates the flexible and complementary nature of PPC services.

Implications for Impact Statement

This case study illustrates the methods and effectiveness of culturally syntonic, interdisciplinary symptom management in pediatric palliative care. It exemplifies how psychological, spiritual, and palliative care efforts, in tandem with tailored medical intervention, can reduce a patient’s total pain despite progressive physical deterioration and disability.
Health Disparities: Barriers to Building Evidence for Effective Palliative End-of-Life Care for Spanish-Speaking Teens With Cancer
Authors: Lyon Maureen E. , Arem Hannah , Jacobs Shana S.
Published: October 2021

Objective: The efficacy of pediatric advance care planning (pACP) has been demonstrated in English-speaking adolescents with cancer and HIV, but not in other populations. The purpose of this study was to (a) adapt and refine a three-session pACP intervention for Spanish-speaking adolescents with cancer and (b) evaluate the feasibility, acceptability, and safety. Method: Using a community-based participatory approach and key informant interviews, we identified important themes: respect for physicians, need for community education about pACP, fear of deportation, and the importance of including family for any pediatric intervention. Results: Using an iterative process, we adapted/refined an existing pACP protocol. The outcome was a culturally adapted and manualized curriculum with a manual of operating procedures, as well as consents, assents, study questionnaires, and a REDCap database in English and Spanish. Questionnaires about spirituality and religion were acceptable. Conclusions: Results suggest that pACP would be feasible, following community education, if delivered during a hospital visit with the patient and family together along with a Spanish-speaking facilitator so a translator is not needed. Support was needed to complete hospital documents, which even in Spanish were not always understandable.

Implications for Impact Statement

We adapted a culturally sensitive version of a pediatric advance care planning program. Challenges were cultural differences and fear of deportation. Study findings highlight the importance of pediatric psychologists’ role as community educators, advocates with legislators, and clinicians committed to tackling taboo subjects and decreasing health disparities.
Ketamine induces opposite changes in AMPA receptor calcium permeability in the ventral tegmental area and nucleus accumbens
Authors: Skiteva Olga , Yao Ning , Chergui Karima
Published: October 2021

Ketamine elicits rapid and durable antidepressant actions in treatment-resistant patients with mood disorders such as major depressive disorder and bipolar depression. The mechanisms might involve the induction of metaplasticity in brain regions associated with reward-related behaviors, mood, and hedonic drive, particularly the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We have examined if ketamine alters the insertion of the GluA2 subunit of AMPA receptors (AMPAR), which determines calcium permeability of the channel, at glutamatergic synapses onto dopamine (DA) neurons in the VTA and spiny projection neurons (SPNs) in the Core region of the NAc. Mice received one injection of either saline or a low dose of ketamine 24 h before electrophysiological recordings were performed. We found that GluA2-lacking calcium-permeable (CP) AMPARs were present in DA neurons in the VTA of mice treated with saline, and that ketamine-induced the removal of a fraction of these receptors. In NAc SPNs, ketamine induced the opposite change, i.e., GluA2-lacking CP-AMPARs were inserted at glutamatergic synapses. Ketamine-induced metaplasticity was independent of group I metabotropic glutamate receptors (mGluRs) because an agonist of these receptors had similar effects on glutamatergic transmission in mice treated with saline and in mice treated with ketamine in both VTA DA neurons and in the NAc. Thus, ketamine reduces the insertion of CP-AMPARs in VTA DA neurons and induces their insertion in the NAc. The mechanism by which ketamine elicits antidepressant actions might thus involve an alteration in the contribution of GluA2 to AMPARs thereby modulating synaptic plasticity in the mesolimbic circuit.
The tyrosine-kinase inhibitor Nintedanib ameliorates autosomal-dominant polycystic kidney disease
Authors: Jamadar Abeda , Suma Sreenath M. , Mathew Sijo , Fields Timothy A. , Wallace Darren P. , Calvet James P. , Rao Reena
Published: October 2021

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by progressive growth of fluid-filled cysts. Growth factors binding to receptor tyrosine kinases (RTKs) stimulate cell proliferation and cyst growth in PKD. Nintedanib, a triple RTK inhibitor, targets the vascular endothelial growth-factor receptor (VEGFR), platelet-derived growth-factor receptor (PDGFR), and fibroblast growth-factor receptor (FGFR), and is an approved drug for the treatment of non-small-cell lung carcinoma and idiopathic lung fibrosis. To determine if RTK inhibition using nintedanib can slow ADPKD progression, we tested its effect on human ADPKD renal cyst epithelial cells and myofibroblasts in vitro, and on Pkd1f/fPkhd1Cre and Pkd1RC/RC, orthologous mouse models of ADPKD. Nintedanib significantly inhibited cell proliferation and in vitro cyst growth of human ADPKD renal cyst epithelial cells, and cell viability and migration of human ADPKD renal myofibroblasts. Consistently, nintedanib treatment significantly reduced kidney-to-body-weight ratio, renal cystic index, cystic epithelial cell proliferation, and blood-urea nitrogen levels in both the Pkd1f/fPkhd1Cre and Pkd1RC/RC mice. There was a corresponding reduction in ERK, AKT, STAT3, and mTOR activity and expression of proproliferative factors, including Yes-associated protein (YAP), c-Myc, and Cyclin D1. Nintedanib treatment significantly reduced fibrosis in Pkd1RC/RC mice, but did not affect renal fibrosis in Pkd1f/fPkhd1Cre mice. Overall, these results suggest that nintedanib may be repurposed to effectively slow cyst growth in ADPKD.
The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle
Authors: Rigillo Giovanna , Basile Valentina , Belluti Silvia , Ronzio Mirko , Sauta Elisabetta , Ciarrocchi Alessia , Latella Lucia , Saclier Marielle , Molinari Susanna , Vallarola Antonio , Messina Graziella , Mantovani Roberto , Dolfini Diletta , Imbriano Carol
Published: October 2021

The transcription factor NF-Y promotes cell proliferation and its activity often declines during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform, majorly associated with cell differentiation. Through the generation of a conditional knock out mouse model that selectively deletes the NF-YA gene in satellite cells, we demonstrate that NF-YA expression is fundamental to preserve the pool of muscle stem cells and ensures robust regenerative response to muscle injury. In vivo and ex vivo, satellite cells that survive to NF-YA loss exit the quiescence and are rapidly committed to early differentiation, despite delayed in the progression towards later states. In vitro results demonstrate that NF-YA-depleted muscle stem cells accumulate DNA damage and cannot properly differentiate. These data highlight a new scenario in stem cell biology for NF-Y activity, which is required for efficient myogenic differentiation.
Age-related mitochondrial alterations in brain and skeletal muscle of the YAC128 model of Huntington disease
Authors: Bečanović Kristina , Asghar Muhammad , Gadawska Izabella , Sachdeva Shiny , Walker David , Lazarowski Eduardo. R. , Franciosi Sonia , Park Kevin H. J. , Côté Hélène C. F. , Leavitt Blair R.
Published: October 2021

Mitochondrial dysfunction and bioenergetics failure are common pathological hallmarks in Huntington’s disease (HD) and aging. In the present study, we used the YAC128 murine model of HD to examine the effects of mutant huntingtin on mitochondrial parameters related to aging in brain and skeletal muscle. We have conducted a cross-sectional natural history study of mitochondrial DNA changes in the YAC128 mouse. Here, we first show that the mitochondrial volume fraction appears to increase in the axons and dendrite regions adjacent to the striatal neuron cell bodies in old mice. Mitochondrial DNA copy number (mtDNAcn) was used as a proxy measure for mitochondrial biogenesis and function. We observed that the mtDNAcn changes significantly with age and genotype in a tissue-specific manner. We found a positive correlation between aging and the mtDNAcn in striatum and skeletal muscle but not in cortex. Notably, the YAC128 mice had lower mtDNAcn in cortex and skeletal muscle. We further show that mtDNA deletions are present in striatal and skeletal muscle tissue in both young and aged YAC128 and WT mice. Tracking gene expression levels cross-sectionally in mice allowed us to identify contributions of age and genotype to transcriptional variance in mitochondria-related genes. These findings provide insights into the role of mitochondrial dynamics in HD pathogenesis in both brain and skeletal muscle, and suggest that mtDNAcn in skeletal muscle tissue may be a potential biomarker that should be investigated further in human HD.
Development of an optogenetic gene sensitive to daylight and its implications in vision restoration
Authors: Watanabe Yoshito , Sugano Eriko , Tabata Kitako , Hatakeyama Akito , Sakajiri Tetsuya , Fukuda Tomokazu , Ozaki Taku , Suzuki Tomoya , Sayama Tatsuki , Tomita Hiroshi
Published: October 2021

Optogenetic gene-mediated therapy for restoring vision is thought to be a useful treatment for blind patients. However, light sensitivity achieved using this gene therapy is inferior to that of daylight vision. To increase light sensitivity, we designed three mutants using a bioinformatics approach. Nucleotide sequences encoding two sites in the extracellular loops (ex1, ex3) of mVChR1 close to simulated ion-conducting pathways were replaced by homologous amino acid-encoding sequences of ChR1 or ChR2. The light sensitivity of ex3mV1 was higher than that of mVChR1 at 405–617 nm. Visual responses were restored in Royal College of Surgeons rats with genetically degenerating photoreceptor cells transfected with ex3mV1Co, wherein transmembrane of sixth (TM6) in ex3mV1 was additionally replaced with the corresponding domain of CoChR; these rats responded to light in the order of μW/mm2. Thus, ex3mV1Co might be useful for the restoration of advanced visual function.
INO-4800 DNA vaccine induces neutralizing antibodies and T cell activity against global SARS-CoV-2 variants
Authors: Andrade Viviane M. , Christensen-Quick Aaron , Agnes Joseph , Tur Jared , Reed Charles , Kalia Richa , Marrero Idania , Elwood Dustin , Schultheis Katherine , Purwar Mansi , Reuschel Emma , McMullan Trevor , Pezzoli Patrick , Kraynyak Kim , Sylvester Albert , Mammen Mammen P. , Tebas Pablo , Joseph Kim J. , Weiner David B. , Smith Trevor R. F. , Ramos Stephanie J. , Humeau Laurent M. , Boyer Jean D. , Broderick Kate E.
Published: October 2021

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine-induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.
Interactions between nascent proteins and the ribosome surface inhibit co-translational folding
Authors: Cassaignau Anaïs M. E. , Włodarski Tomasz , Chan Sammy H. S. , Woodburn Lauren F. , Bukvin Ivana V. , Streit Julian O. , Cabrita Lisa D. , Waudby Christopher A. , Christodoulou John
Published: October 2021

Most proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain. The strongest interactions are found for a C-terminal segment that is essential for folding, and we demonstrate quantitative agreement between the strength of this interaction and the energetics of the co-translational folding process itself. Mutations in this region that reduce the extent of binding result in a shift in the co-translational folding equilibrium towards the native state. Our results therefore demonstrate that a competition between folding and binding provides a simple, dynamic mechanism for the modulation of co-translational folding by the ribosome.
Microdrilled tapers to enhance optical fiber lasers for sensing
Authors: Perez-Herrera R. A. , Bravo M. , Roldan-Varona P. , Leandro D. , Rodriguez-Cobo L. , Lopez-Higuera J. M. , Lopez-Amo M.
Published: October 2021

In this work, an experimental analysis of the performance of different types of quasi-randomly distributed reflectors inscribed into a single-mode fiber as a sensing mirror is presented. These artificially-controlled backscattering fiber reflectors are used in short linear cavity fiber lasers. In particular, laser emission and sensor application features are analyzed when employing optical tapered fibers, micro-drilled optical fibers and 50 μm-waist or 100 μm-waist micro-drilled tapered fibers (MDTF). Single-wavelength laser with an output power level of about 8.2 dBm and an optical signal-to-noise ratio of 45 dB were measured when employing a 50 μm-waist micro-drilled tapered optical fiber. The achieved temperature sensitivities were similar to those of FBGs; however, the strain sensitivity improved more than one order of magnitude in comparison with FBG sensors, attaining slope sensitivities as good as 18.1 pm/με when using a 50 μm-waist MDTF as distributed reflector.
Generating synthetic contrast enhancement from non-contrast chest computed tomography using a generative adversarial network
Authors: Choi Jae Won , Cho Yeon Jin , Ha Ji Young , Lee Seul Bi , Lee Seunghyun , Choi Young Hun , Cheon Jung-Eun , Kim Woo Sun
Published: October 2021

This study aimed to evaluate a deep learning model for generating synthetic contrast-enhanced CT (sCECT) from non-contrast chest CT (NCCT). A deep learning model was applied to generate sCECT from NCCT. We collected three separate data sets, the development set (n = 25) for model training and tuning, test set 1 (n = 25) for technical evaluation, and test set 2 (n = 12) for clinical utility evaluation. In test set 1, image similarity metrics were calculated. In test set 2, the lesion contrast-to-noise ratio of the mediastinal lymph nodes was measured, and an observer study was conducted to compare lesion conspicuity. Comparisons were performed using the paired t-test or Wilcoxon signed-rank test. In test set 1, sCECT showed a lower mean absolute error (41.72 vs 48.74; P < .001), higher peak signal-to-noise ratio (17.44 vs 15.97; P < .001), higher multiscale structural similarity index measurement (0.84 vs 0.81; P < .001), and lower learned perceptual image patch similarity metric (0.14 vs 0.15; P < .001) than NCCT. In test set 2, the contrast-to-noise ratio of the mediastinal lymph nodes was higher in the sCECT group than in the NCCT group (6.15 ± 5.18 vs 0.74 ± 0.69; P < .001). The observer study showed for all reviewers higher lesion conspicuity in NCCT with sCECT than in NCCT alone (P ≤ .001). Synthetic CECT generated from NCCT improves the depiction of mediastinal lymph nodes.
Deglacial patterns of South Pacific overturning inferred from 231Pa and 230Th
Authors: Ronge Thomas A. , Lippold Jörg , Geibert Walter , Jaccard Samuel L. , Mieruch-Schnülle Sebastian , Süfke Finn , Tiedemann Ralf
Published: October 2021

The millennial-scale variability of the Atlantic Meridional Overturning Circulation (AMOC) is well documented for the last glacial termination and beyond. Despite its importance for the climate system, the evolution of the South Pacific overturning circulation (SPOC) is by far less well understood. A recently published study highlights the potential applicability of the 231Pa/230Th-proxy in the Pacific. Here, we present five sedimentary down-core profiles of 231Pa/230Th-ratios measured on a depth transect from the Pacific sector of the Southern Ocean to test this hypothesis using downcore records. Our data are consistent with an increase in SPOC as early as 20 ka that peaked during Heinrich Stadial 1. The timing indicates that the SPOC did not simply react to AMOC changes via the bipolar seesaw but were triggered via Southern Hemisphere processes.
Role of organic cation orientation in formamidine based perovskite materials
Authors: Liu Siyu , Wang Jing , Hu Zhe , Duan Zhongtao , Zhang Hao , Zhang Wanlu , Guo Ruiqian , Xie Fengxian
Published: October 2021

The rotation of organic cations is considered to be an important reason for the dynamic changes in stability and photoelectric properties of organic perovskites. However, the specific effect of organic cations rotation on formamidine based perovskite is still unknown. In our work, first-principles calculations based on density functional theory are used to examine the effect of the rotation of formamidine cations in FAPbI3 and FA0.875Cs0.125PbI3. We have comprehensively calculated the structure, electronic and optical properties of them. We found a coupling effect between formamidine cations rotation and cesium atom. This coupling effect changes the inclination angle of octahedron to regulate electron distribution, band gaps, and optical absorption. Hence, changing the cation orientation and substitution atom is a feasible way to dynamically adjust the energy band, dielectric constant and absorption edge of perovskite. Preparing perovskite with tunable properties is just around the corner through this way.
Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis
Authors: Becker Kerstin , Heinemann Klaas , Imthurn Bruno , Marions Lena , Moehner Sabine , Gerlinger Christoph , Serrani Marco , Faustmann Thomas
Published: October 2021

Endometriosis is a chronic disease that requires a suitable, lifelong treatment. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is to date the largest real-world, non-interventional study investigating hormonal management of endometriosis. We describe women’s experiences of endometriosis in the real world by considering their symptoms and the diagnostic process in their healthcare setting. Overall, 27,840 women were enrolled from six European countries via networks of gynecologists or specialized centers. Of these, 87.8% of women were diagnosed based on clinical symptoms; the greatest and lowest proportions of women were in Russia (94.1%) and Germany (61.9%), respectively. Most women (82.8%) experienced at least one of the triad of endometriosis-associated pain symptoms: pelvic pain, pain after/during sexual intercourse, and painful menstrual periods. The most frequently reported endometriosis-associated symptoms were painful periods (61.8%), heavy/irregular bleeding (50.8%), and pelvic pain (37.2%). Women reported that endometriosis impacted their mood; 55.6% reported feeling “down”, depressed, or hopeless, and 53.2% reported feeling like a failure or having let down family/friends. VIPOS broadens our understanding of endometriosis based on real-world data by exploring the heterogeneity of symptoms women with endometriosis experience and the differences in diagnostic approaches between European countries.

Trial registration: ClinicalTrials.gov, NCT01266421; registered 24 December 2010. Registered in the European Union electronic Register of Post-Authorisation Studies as number 1613.
Pan-cancer analysis of the prognostic and immunological role of PSMB8
Authors: Chen Danxiang , Jin Cong , Dong Xubin , Wen Jialiang , Xia Erjie , Wang Qingxuan , Wang Ouchen
Published: October 2021

Recently some evidence has demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of the PSMB8 expression profile among 33 types of cancer in the TCGA database. The results show that overexpression of PSMB8 was associated with poor clinical outcomes in overall survival (Sartorius et al. in Oncogene 35(22):2881–2892, 2016), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightforwardly in the form of immune scores, tumor-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumor mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative PCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for prognosis determination in multiple cancers.
DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes
Authors: Hatanaka Yui , Niinuma Takeshi , Kitajima Hiroshi , Nishiyama Koyo , Maruyama Reo , Ishiguro Kazuya , Toyota Mutsumi , Yamamoto Eiichiro , Kai Masahiro , Yorozu Akira , Sekiguchi Shohei , Ogi Kazuhiro , Dehari Hironari , Idogawa Masashi , Sasaki Yasushi , Tokino Takashi , Miyazaki Akihiro , Suzuki Hiromu
Published: October 2021

Long noncoding RNAs (lncRNAs) are deeply involved in cancer development. We previously reported that DLEU1 (deleted in lymphocytic leukemia 1) is one of the lncRNAs overexpressed in oral squamous cell carcinoma (OSCC) cells, where it exhibits oncogenic activity. In the present study, we further clarified the molecular function of DLEU1 in the pathogenesis of OSCC. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that DLEU1 knockdown induced significant changes in the levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac) in OSCC cells. Notably, DLEU1 knockdown suppressed levels of H3K4me3/ H3K27ac and expression of a number of interferon-stimulated genes (ISGs), including IFIT1, IFI6 and OAS1, while ectopic DLEU1 expression activated these genes. Western blot analysis and reporter assays suggested that DLEU1 upregulates ISGs through activation of JAK-STAT signaling in OSCC cells. Moreover, IFITM1, one of the ISGs induced by DLUE1, was frequently overexpressed in primary OSCC tumors, and its knockdown inhibited OSCC cell proliferation, migration and invasion. These findings suggest that DLEU1 exerts its oncogenic effects, at least in part, through activation of a series ISGs in OSCC cells.
Antiferromagnetic and ferromagnetic spintronics and the role of in-chain and inter-chain interaction on spin transport in the Heisenberg ferromagnet
Authors: Lima L. S.
Published: October 2021

Spin-transport and current-induced torques in ferromagnet heterostructures given by a ferromagnetic domain wall are investigated. Furthermore, the continuum spin conductivity is studied in a frustrated spin system given by the Heisenberg model with ferromagnetic in-chain interaction $$J_1<0$$

J
1

<
0

between nearest neighbors and antiferromagnetic next-nearest-neighbor in-chain interaction $$J_2>0$$

J
2

>
0

with aim to investigate the effect of the phase diagram of the critical ion single anisotropy $$D_c$$

D
c

as a function of $$J_2$$

J
2

on conductivity. We consider the model with the moderate strength of the frustrating parameter such that in-chain spin-spin correlations that are predominantly ferromagnetic. In addition, we consider two inter-chain couplings $$J_{\perp ,y}$$

J

⊥
,
y

and $$J_{\perp ,z}$$

J

⊥
,
z

, corresponding to the two axes perpendicular to chain where ferromagnetic as well as antiferromagnetic interactions are taken into account.