bluuebunny/crossref_metadata_2025 huggingface dataset:
Garpenbergite, Mn6□As5+Sb5+O10(OH)2, a new mineral related to manganostibite, from the Garpenberg Zn–Pb–Ag deposit, Sweden
Authors: Holtstam Dan , Bindi Luca , Förster Hans-Jürgen , Karlsson Andreas , Gatedal Kjell
Published: January 2022

Garpenbergite is a new mineral (IMA2020-099) from the Garpenberg Norra mine, Hedemora, Dalarna, Sweden. It occurs with carlfrancisite and minor stibarsen, paradocrasite and filipstadite in a fractured skarn matrix of granular jacobsite, alleghanyite, kutnohorite and dolomite. Crystals are short-prismatic, up to 1.5 mm in length. They have a blackish to greyish brown colour, and are lustrous semi-opaque, with brown streak. Garpenbergite is brittle, with an uneven to subconchoidal fracture. Cleavage is distinct on {010}. Hardness ≈ 5 (Mohs) and VHN100 = 650(40). Dcalc = 4.47(1) g⋅cm−3, overall ncalc = 1.85. Maximum specular reflectance values (%) obtained are 9.2 (470 nm), 9.1 (546 nm), 9.0 (589 nm) and 8.9 (650 nm). The empirical chemical formula of garpenbergite, based on electron microprobe data, is (Mn2+3.97Mg1.48Mn3+0.26Zn0.29)Σ6.00(As0.89Fe3+0.04Mn3+0.06Si0.01)Σ1.00(Sb0.98Fe0.02)Σ1O10[(OH)1.99Cl0.01]Σ2.00. The five strongest Bragg peaks in the powder X-ray diffraction pattern [d, Å (I, %) (hkl)] are 3.05 (30) (002), 2.665 (100) (161), 2.616 (40) (301), 2.586 (25) (251) and 1.545 (45) (462). The orthorhombic unit-cell dimensions (in Å) are a = 8.6790(9), b = 18.9057(19) and c = 6.1066(6), with V = 1001.99(18) Å3 for Z = 4. The crystal structure was refined from single-crystal X-ray diffraction data in the space-group Ibmm to R1 = 3.7% for 957 reflections. Garpenbergite, ideally Mn6As5+Sb5+O10(OH)2, is isostructural with manganostibite, Mn7AsSbO12, but possesses a cation vacancy (□) at an octahedrally coordinated structural site; the two minerals are thus related by the exchange Mn2+ + 2O2– → □ + 2(OH)–. The presence of hydroxyl groups is supported by vibration bands at 3647 and 3622 cm−1 in the Raman spectrum of garpenbergite and by bond-valence considerations.
Neural transcriptomic signature of chronic wasting disease in white-tailed deer
Authors: O’Hara Eóin , Herbst Allen , Kommadath Arun , Aiken Judd M. , McKenzie Debbie , Goodarzi Negin , Skinner Pamela , Stothard Paul
Published: January 2022

Background

The increasing prevalence and expanding geographical range of the chronic wasting disease (CWD) panzootic in cervids is threatening human, animal, environmental and economic health. The pathogenesis of CWD in cervids is, however, not well understood. We used RNA sequencing (RNA-seq) to compare the brain transcriptome from white-tailed deer (WTD; Odocoileus virginianus) clinically affected with CWD (n = 3) to WTD that tested negative (n = 8) for CWD. In addition, one preclinical CWD+ brain sample was analyzed by RNA-seq.

Results

We found 255 genes that were significantly deregulated by CWD, 197 of which were upregulated. There was a high degree of overlap in differentially expressed genes (DEGs) identified when using either/both the reference genome assembly of WTD for mapping sequenced reads to or the better characterized genome assembly of a closely related model species, Bos taurus. Quantitative PCR of a subset of the DEGs confirmed the RNA-seq data. Gene ontology term enrichment analysis found a majority of genes involved in immune activation, consistent with the neuroinflammatory pathogenesis of prion diseases. A metagenomic analysis of the RNA-seq data was conducted to look for the presence of spiroplasma and other bacteria in CWD infected deer brain tissue.

Conclusions

The gene expression changes identified highlight the role of innate immunity in prion infection, potential disease associated biomarkers and potential targets for therapeutic agents. An association between CWD and spiroplasma infection was not found.
Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial
Authors: Ibrahim Mohamed , Elnabtity Ali M. , Hegab Ahmed , Alnujaidi Omar A. , El Sanea Osama
Published: January 2022

Background

It is debatable whether opioid-free anaesthesia (OFA) is better suited than multimodal analgesia (MMA) to achieve the goals of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic sleeve gastrectomy.

Methods

In all patients, anaesthesia was conducted with an i.v. induction with propofol (2 mg. kg-1), myorelaxation with cisatracurium (0.15 mg.kg-1), in addition to an ultrasound-guided bilateral oblique subcostal transverse abdominis plane block. In addition, patients in the OFA group (n = 51) received i.v. dexmedetomidine 0.1 μg.kg-1 and ketamine (0.5 mg. kg-1) at induction, then dexmedetomidine 0.5 μg. kg-1.h-1, ketamine 0.5 mg.kg-1.h-1, and lidocaine 1 mg. kg-1.h-1 for maintenance, while patients in the MMA group (n = 52) had only i.v. fentanyl (1 μg. kg-1) at induction. The primary outcome was the quality of recovery assessed by QoR-40, at the 6th and the 24th postoperative hour. Secondary outcomes were postoperative opioid consumption, time to ambulate, time to tolerate oral fluid, and time to readiness for discharge.

Results

At the 6th hour, the QoR-40 was higher in the OFA than in the MMA group (respective median [IQR] values: 180 [173–195] vs. 185 [173–191], p < 0.0001), but no longer difference was found at the 24th hour (median values = 191 in both groups). OFA also significantly reduced postoperative pain and morphine consumption (20 mg [1–21] vs. 10 mg [1–11], p = 0.005), as well as time to oral fluid tolerance (238 [151–346] vs. 175 min [98–275], p = 0.022), and readiness for discharge (505 [439–626] vs. 444 min [356–529], p = 0.001), but did not influence time to ambulate.

Conclusion

While regional anaesthesia achieved most of the intraoperative analgesia, avoiding intraoperative opioids with the help of this OFA protocol was able to improve several sensible parameters of postoperative functional recovery, thus improving our knowledge on the OFA effects.

Clinical trial number

Registration number NCT04285255.
Stability of context in sport and exercise across educational transitions in adolescence: hello work, goodbye sport club?
Authors: Gut Vanessa , Schmid Julia , Imbach Lars , Conzelmann Achim
Published: January 2022

Background

The present study firstly aimed to identify context patterns in sport and exercise among adolescents at lower and upper secondary education. The organisational, social and competitive contexts of leisure-time sport and exercise were included as pattern indicators. The second aim was to examine the stability of these patterns across educational transition. The last aim was to investigate whether a subjective evaluation of the transition influences whether people stay in the same pattern across time.

Methods

One-year longitudinal data of 392 adolescents were analysed.

Results

Both before and after the educational transition, four context patterns were identified: the traditional competitive club athletes with friends, the self-organised individualists, the non-club-organised sportspersons and the mostly inactives. More than half of the individuals stayed in the same pattern across time. When individuals changed pattern, their change was most often from the self-organised individualists and the non-club-organised to the mostly inactives. A subjective evaluation of the transition influenced the stability of only the traditional competitive club athletes with friends. The chance of these people staying in the same pattern decreased with increased transitional stress.

Conclusions

Knowledge about the stability and change of context patterns can be used to make recommendations for policy strategies and to develop more individually-tailored promotion programs.
Impact of Dutch COVID-19 restrictive policy measures on physical activity behavior and identification of correlates of physical activity changes: a cohort study
Authors: Schoofs Merle C. A. , Bakker Esmée A. , de Vries Femke , Hartman Yvonne A. W. , Spoelder Marcia , Thijssen Dick H. J. , Eijsvogels Thijs M. H. , Buffart Laurien M. , Hopman Maria T. E.
Published: January 2022

Background

Identification of characteristics of individuals that are related to decreases in physical activity (PA) levels during lockdown is needed to develop targeted-interventions. This study aims to evaluate changes in domain-specific (i.e. leisure time, transportation, occupational, and household) and total PA due to the Dutch COVID-19 lockdown, which started on March 15 2020. Furthermore, we aim to identify demographic, health-related, and psychological correlates of these changes.

Methods

Individuals who participated in the Nijmegen Exercise Study during 2017-2019 were invited to this study, which was conducted between April 16 and May 12 2020. Participant characteristics (i.e. age, sex, body mass index (BMI), marital status, education, household composition, and occupation status), living environment (i.e. housing type and degree of urbanization), psychological characteristics (i.e. resilience, outcome expectations, vitality, and mental health), and medical history were collected via an online questionnaire. Short Questionnaire to Assess Health-enhancing physical activity was used to assess PA behavior before and during lockdown. Wilcoxon signed-rank test was used to compare PA levels, in metabolic equivalent of task (MET)-minutes per week (min/wk), before and during lockdown. Multivariable linear regression analyses were performed to examine correlates of PA changes.

Results

4033 participants (57% male; 59 ± 13 years) were included. PA decreased significantly during lockdown with mean ± SD changes of 393 ± 2735 MET-min/wk for total, 133 ± 785 MET-min/wk for transportation, 137 ± 1469 MET-min/wk for occupation, and 136 ± 1942 MET-min/wk for leisure time PA. Household PA did not change significantly. Unemployment, COVID-19-related occupational changes, higher BMI, and living in an apartment or semi-detached/terraced house were significantly related to larger decreases in total and domain-specific PA. Higher vitality was related to smaller decreases in total and domain-specific PA. Higher age was significantly associated with a larger decrease in leisure time PA. Lower education was associated with smaller decreases in transportation and occupational PA compared to higher education.

Conclusion

PA levels significantly reduced during lockdown compared to before lockdown. Declines were observed during transportation and occupation, but were not compensated by an increase in leisure time PA. We identified subgroups that were more susceptible to reductions in domain-specific or total PA levels and should therefore be encouraged to increase their PA levels during lockdown.
Trends in the development process of clinical practice guidelines: a questionnaire survey for the guideline development groups in Japan
Authors: Hatakeyama Yosuke , Seto Kanako , Hirata Koki , Onishi Ryo , Matsumoto Kunichika , Hasegawa Tomonori
Published: January 2022

Background

Clinical practice guidelines (CPGs) are representative methods for promoting healthcare standardization and improving its quality. Previous studies on the CPG (published by 2006) development process in Japan reported that the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of evidence on Japanese patients should be improved for the efficient CPG development. This study aimed to clarify the trends of CPG development process in Japan, focusing on the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of Japanese evidence.

Methods

A cross-sectional questionnaire survey was conducted for CPG development groups to collect information on the development activities of the CPGs published from 2012 to 2019. These CPGs were identified from the Japanese guideline clearinghouse. The questionnaire included the questions on composing the group, securing funding sources, collecting and appraising the research evidence, and the difficulties in the CPG development process. The questionnaires were distributed to the chairpersons of the CPG development groups through postal mail from November 2020 to January 2021. Combining the data from the current survey with those of previous studies reporting the development process of CPGs published by 2011, we analyzed the trend in the CPG development process.

Results

Of the total 265 CPGs included in the analysis, 164 (response rate: 41.4%) were from the current survey and 101 (response rate: 44.5%) were from previous studies. Among these, 40 (15.1%) were published by 2005, 47 (17.7%) in 2006–2010, 77 (29.1%) in 2011–2015, and 101 (38.1%) in 2016–2019. The proportion of CPGs involving methodologists did not increase through the publication periods. The proportion of CPGs involving patients almost doubled from the first period (15.9%) to the fourth period (32.4%). The yield rates of the articles did not change through the publication periods. The difficulty in “Coping with the paucity of Japanese evidence” has been improving consistently (69.2% in the first period to 37.4% in the fourth period).

Conclusions

Our results suggest the need for methodological improvement in the efficient collection and appraisal of evidence and in the system assigning experts to the CPG development groups.
Postbariatric EArly discharge Controlled by Healthdot (PEACH) trial: study protocol for a preference-based randomized trial
Authors: Scheerhoorn Jai , van Ede Lisa , Luyer Misha D. P. , Buise Marc P. , Bouwman R. Arthur , Nienhuijs Simon W.
Published: January 2022

Introduction

Performing bariatric surgery in a daycare setting has a potential reduction in hospital costs and increase in patients’ satisfaction. Although the feasibility and safety of such care pathway has already been proven, its implementation is hampered by concerns about timely detection of short-term complications. This study is designed to evaluate a combined outcome measurement in outpatient bariatric surgery supplemented by a novel wireless remote monitoring system versus current standard of care.

Methods and analysis

A total of 200 patients with multidisciplinary team approval for primary bariatric surgery will be assigned based on their preference to one of two postoperative trajectories: (1) standard of in-hospital care with discharge on the first postoperative day or (2) same day discharge with ongoing telemonitoring up to 7 days after surgery. The device (Healthdot R Philips) transfers heart rate, respiration rate, activity, and body posture of the patient continuously by LoRaWan network to our hospital’s dashboard (Philips Guardian). The primary outcome is a composite outcome measure within 30 days postoperative based on mortality, mild and severe complications, readmission, and prolonged length-of-stay. Secondary outcomes include patients’ satisfaction and data handling dimensions.

Trial registration

ClinicalTrials.govNCT04754893, Registered on 12 February 2021.
Effect of perioperative cognitive behavioural therapy on chronic post-surgical pain among breast cancer patients with high pain catastrophising characteristics: protocol for a double-blinded randomised controlled trial
Authors: Moorthy Aneurin , Lowry Damien , Edgley Carla , Casey Maire-Brid , Buggy Donal
Published: January 2022

Background

Surgery is regarded as the primary treatment for breast cancer. Chronic post-surgical pain (CPSP) is a recognised complication after breast cancer surgery, and it is estimated to affect 20–30% of women. Pain catastrophizing has emerged as one of the most influential psychological variables associated with CPSP.

Methods

This trial will be a single-centre, prospective, double-blinded, superiority, randomised controlled trial (RCT). Patients scheduled for elective breast cancer surgery (wide local excision or mastectomy with or without axillary lymph node dissection) will be screened preoperatively for high pain catastrophising. Patients with high pain catastrophising, defined as a score of ≥ 24 on the Pain Catastrophising Scale will be deemed eligible for inclusion in the study. Participants will be randomly assigned to receive either a cognitive behavioural therapy or an educational mindfulness based programme during their perioperative period. The primary outcome is the Brief Pain Inventory short form average pain severity score at 3 months postoperatively. Secondary outcomes include patient-reported quality of recovery at days 1–2 after surgery, levels of pain catastrophising, reported depressed mood and anxiety.

Discussion

To the best of our knowledge, this protocol describes the first RCT which directly examines the effect of perioperative cognitive behavioural therapy on CPSP among breast cancer patients with high pain catastrophising characteristics. The outcomes of this trial may have significant implications for these patients because perioperative cognitive behavioural therapy has the potential to become an important perioperative intervention to complement patient management.

Trial registration

ClinicalTrials.govNCT04924010. Registered on 11 June 2021. All item from the World Health Organisation Trial Registration Data set have been included.
Transradial peripheral vascular intervention using Fowler’s position and Terumo R2P system for patients with heart failure: two case reports
Authors: Nakamura Akihiro , Sato Kenjiro , Endo Hideaki
Published: January 2022

Background

Positioning a patient on the catheterization table is important for proper cardiac or respiratory function during peripheral vascular interventions. Fowler’s position, where the patient’s head is a 45° angle, is more effective in reducing venous blood volume returning to the heart from the periphery compared with the supine position. The Terumo R2P system has been developed for transradial peripheral vascular interventions.

Case presentation

Two patients with heart failure (a 75-year-old Japanese female and a 74-year-old Japanese male) underwent lower-extremity peripheral vascular interventions in Fowler’s position to prevent worsening heart failure. Because their head position was opposite the C-arm of the X-ray machine, the left radial artery was selected as the access site. The Terumo R2P system was used for transradial peripheral vascular intervention. We successfully treated superficial artery diseases with long shaft balloons and rapid-exchange Terumo R2P Misago stents.

Conclusions

Although lower-extremity peripheral vascular intervention using Fowler’s position and the Terumo R2P system has several limitations, including device availability and technical complexity, it may be effective for particular patients who have higher risk of worsening heart failure in the supine position.
High Power Sugar Fuel Cells Using PEDOT*PSS, CNT and PtRu Composite Anode
Authors: Kaneto Keiichi , Uto Sadahito
Published: January 2022

Output characteristics of sugars/KOH fuel cells using PEDOT*PSS, CNT, and PtRu composite (anode)/cellophane/Pt (cathode)/air have been studied. The maximum power density of glucose demonstrated 60 mWcm−2, being the best in the world. The relative outputs were 1, 0.37, 0.51, 0.42, and 0.006 for glucose, fructose, lactose, maltose, and sucrose, respectively, depending on the reducibility of sugars. The hydrolysis of sucrose with acids resulted in the enhancement of output. The coulombic and energetic conversion efficiencies are discussed comparing experimental and theoretical estimations.
Εφαρμογή πολυφασματικών μεθόδων στην ερμηνεία και μοντελοποίηση του πεδίου βαρύτητας
Authors: Πατλάκης Κωνσταντίνος
Published: January 2022

Ο ολοένα αυξανόμενος αριθμός δορυφορικών μοντέλων και μοντέλων συνδυασμού σε σύνολο σφαιρικών αρμονικών συντελεστών που αποτυπώνουν το ανάπτυγμα του πεδίου βαρύτητας ως ένα μέγιστο βαθμό και τα οποία ανακτώνται από την ανάλυση δεδομένων διαδορυφορικών παρατηρήσεων και βαθμιδομετρίας ή από τον συνδυασμό δορυφορικών δεδομένων με επίγεια πληροφορία, θέτει νέες προκλήσεις στην ερμηνεία και μοντελοποίηση του πεδίου βαρύτητας. Στόχος της παρούσας διατριβής είναι η παρουσίαση μιας λεπτομερούς και αναλυτικής αξιολόγησης και ποσοτικής ερμηνείας, τόσο στον χώρο του φάσματος όσο και στον χώρο των αποστάσεων, σχεδόν όλων των διαθέσιμων σύγχρονων μοντέλων του πεδίου βαρύτητας, περιλαμβάνοντας μοντέλα CHAMP, GRACE, GOCE και μοντέλα συνδυασμού, με σκοπό τον εντοπισμό πεπερασμένων φασματικών περιοχών όπου τα μοντέλα παρουσιάζουν ιδιαίτερα στατιστικά χαρακτηριστικά. Οι στατιστικές ποσότητες που χρησιμοποιούνται στην παρούσα εργασία και εκφράζονται είτε συναρτήσει των συντελεστών των μοντέλων είτε των σφαλμάτων τους, ή εκφράζονται ανά βαθμό ή τάξη ή με τη μορφή κάποιας παράγωγης ποσότητας του πεδίου βαρύτητας, ποσοτικοποιούν τη συσχέτιση μεταξύ των δορυφορικών μοντέλων και διάφορων τοπογραφικών/ισοστατικών μοντέλων, προσδιορίζοντας πεπερασμένες φασματικές περιοχές όπου παρατηρείται έντονη συσχέτιση. Η διερεύνηση του επιπέδου συσχέτισης μεταξύ δορυφορικών και τοπογραφικών/ισοστατικών μοντέλων θέτει μια γερή βάση για την ερμηνεία και μοντελοποίηση του πεδίου βαρύτητας. Τα σύγχρονα τοπογραφικά μοντέλα έχουν ολοένα και μεγαλύτερο μέγιστο βαθμό ανάπτυξης με τα πιο πρόσφατα διαθέσιμα να φτάνουν το βαθμό 5480. Σε αυτό το μέγεθος για τον βαθμό ενός μοντέλου οι προσαρτημένες συναρτήσεις Legendre δεν μπορούν να υπολογιστούν εξαιτίας των αριθμητικών προβλημάτων της υποεκχείλισης (underflow) και της υπερεκχείλισης (overflow) τα οποία βασίζονται στο σύστημα κινητής υποδιαστολής που χρησιμοποιούν οι ηλεκτρονικοί υπολογιστές. Η παρούσα διατριβή στοχεύει στην ανάλυση υπαρχόντων μεθόδων για τον υπολογισμό των προσαρτημένων συναρτήσεων Legendre. Επιπλέον, διερευνά το αν οι μέθοδοι αυτές επιλύουν το αριθμητικό πρόβλημα προσωρινά ή μόνιμα και τελικά προτείνει νέες μεθόδους αλλά και τροποποιήσεις στις ήδη υπάρχουσες.
De um iluminismo colonial ou outros aspectos da ilustração no Brasil: circulação de ideias, identidades locais e historiografias brasílicas.
Authors: Silva Bruno
Published: January 2022

O presente artigo aborda a construção de identidades regionais na sociedade colonial da América portuguesa. Através da análise do valor discursivo das crônicas lusobrasileiras confeccionadas ao longo do século XVIII, busca-se traçar tal panorama e os planos de integração do Brasil a Portugal nessas narrativas. Destaca-se, também, as invenções genealógicas locais frente à miscigenação sociorracial desta formação histórica.
Redes Transimperiais no Comércio do Atlântico Sul: o exemplo dos ingleses lisboetas no Rio de Janeiro durante a segunda metade do século XVIII.
Authors: PESAVENTO FABIO
Published: January 2022

O advento da descoberta do ouro, em fins do século XVII transformou a economia colonial. O papel das redes de negócio neste processo foi decisivo. Analisar os agentes envolvidos nessas transações e suas principais agências foi o objetivo do artigo. Os resultados mostraram que as redes transimperiais eram operadas por importantes negociantes estrangeiros, estabelecidos em Lisboa e com forte presença na praça fluminense.
Hyperosmolar Therapy for Diabetic Hyperosmolar Ketoacidosis
Authors: Heldeweg Micah LA , Drossaers Joris R , Berend Kenrick
Published: January 2022

Hyperglycaemic hyperosmolar state (HHS) and diabetic ketoacidosis (DKA) features can occur simultaneously in 27% of diabetic emergencies and have a two-fold increased risk of death. Despite the high prevalence of this combination, recommended treatments from leading guidelines may not be compatible with the clinical picture.  A 36-year-old man presented with explicit concurrent HHS and DKA. The recommended treatment with simultaneous insulin and volume repletion was followed but resulted in an excessively rapid decline in serum osmolarity. Hyperosmolar therapy (NaCl 3%) was initiated to mitigate the risk of potentially fatal cerebral osmotic shifts. The concomitant presence of DKA and HHS leads to a treatment dilemma with a high risk of excessive osmolarity shifts. More evidence is needed, but it is reasonable to initiate tailored treatment to avoid osmolarity reduction rates exceeding the hypernatraemia-based limit of 24 mOsm/l/day. Hyperosmolar therapy can be considered but requires frequent monitoring of electrolytes and osmolarity.
Significant sensing performance of an all-silicon terahertz metasurface chip for Bacillus thuringiensis Cry1Ac protein
Authors: Cui Zijian , Wang Yue , Shi Yongqiang , Zhu Yongqiang , Zhang Dachi , Hong Zhiqi , Feng Xuping
Published: January 2022

The promising prospect of a terahertz metasurface in sensing and detection applications has attracted increasing attention because of its ability to overcome the classical diffraction limit and the enhancement of field intensity. In this work, a novel scheme based on an all-silicon terahertz plasmon metasurface is proposed and experimentally demonstrated to be a highly sensitive biosensor for the Bacillus thuringiensis Cry1Ac toxin. The regression coefficients between Bacillus thuringiensis protein concentrations and the spectral resonance intensity and frequency were 0.8988 and 0.9238, respectively. The resonance amplitude variation and frequency shift of the metasurface were investigated in terms of both thickness and permittivity change of the analyte, which reflected the protein residue in the actual process. Moreover, the reliability and stability of the metasurface chip were verified by time period, temperature, and humidity control. These results promise the ability of the proposed metasurface chip as a Bacillus thuringiensis protein sensor with high sensitivity and stability. In addition, this novel device strategy provides opportunities for the advancement of terahertz functional applications in the fields of biochemical sensing and detection.
Single-cell sequencing reveals lineage-specific dynamic genetic regulation of gene expression during human cardiomyocyte differentiation
Authors: Elorbany Reem , Popp Joshua M. , Rhodes Katherine , Strober Benjamin J. , Barr Kenneth , Qi Guanghao , Gilad Yoav , Battle Alexis
Published: January 2022

Dynamic and temporally specific gene regulatory changes may underlie unexplained genetic associations with complex disease. During a dynamic process such as cellular differentiation, the overall cell type composition of a tissue (or an in vitro culture) and the gene regulatory profile of each cell can both experience significant changes over time. To identify these dynamic effects in high resolution, we collected single-cell RNA-sequencing data over a differentiation time course from induced pluripotent stem cells to cardiomyocytes, sampled at 7 unique time points in 19 human cell lines. We employed a flexible approach to map dynamic eQTLs whose effects vary significantly over the course of bifurcating differentiation trajectories, including many whose effects are specific to one of these two lineages. Our study design allowed us to distinguish true dynamic eQTLs affecting a specific cell lineage from expression changes driven by potentially non-genetic differences between cell lines such as cell composition. Additionally, we used the cell type profiles learned from single-cell data to deconvolve and re-analyze data from matched bulk RNA-seq samples. Using this approach, we were able to identify a large number of novel dynamic eQTLs in single cell data while also attributing dynamic effects in bulk to a particular lineage. Overall, we found that using single cell data to uncover dynamic eQTLs can provide new insight into the gene regulatory changes that occur among heterogeneous cell types during cardiomyocyte differentiation.
Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study
Authors: Hayes Bryony L. , Robinson Timothy , Kar Siddhartha , Ruth Katherine S. , Tsilidis Konstantinos K. , Frayling Timothy , Murray Anna , Martin Richard M. , Lawlor Deborah A. , Richmond Rebecca C.
Published: January 2022

Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10−8) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates.
Individualized spatial network predictions using Siamese convolutional neural networks: A resting-state fMRI study of over 11,000 unaffected individuals
Authors: Hassanzadeh Reihaneh , Silva Rogers F. , Abrol Anees , Salman Mustafa , Bonkhoff Anna , Du Yuhui , Fu Zening , DeRamus Thomas , Damaraju Eswar , Baker Bradley , Calhoun Vince D.
Published: January 2022

Individuals can be characterized in a population according to their brain measurements and activity, given the inter-subject variability in brain anatomy, structure-function relationships, or life experience. Many neuroimaging studies have demonstrated the potential of functional network connectivity patterns estimated from resting functional magnetic resonance imaging (fMRI) to discriminate groups and predict information about individual subjects. However, the predictive signal present in the spatial heterogeneity of brain connectivity networks is yet to be extensively studied. In this study, we investigate, for the first time, the use of pairwise-relationships between resting-state independent spatial maps to characterize individuals. To do this, we develop a deep Siamese framework comprising three-dimensional convolution neural networks for contrastive learning based on individual-level spatial maps estimated via a fully automated fMRI independent component analysis approach. The proposed framework evaluates whether pairs of spatial networks (e.g., visual network and auditory network) are capable of subject identification and assesses the spatial variability in different network pairs’ predictive power in an extensive whole-brain analysis. Our analysis on nearly 12,000 unaffected individuals from the UK Biobank study demonstrates that the proposed approach can discriminate subjects with an accuracy of up to 88% for a single network pair on the test set (best model, after several runs), and 82% average accuracy at the subcortical domain level, notably the highest average domain level accuracy attained. Further investigation of our network’s learned features revealed a higher spatial variability in predictive accuracy among younger brains and significantly higher discriminative power among males. In sum, the relationship among spatial networks appears to be both informative and discriminative of individuals and should be studied further as putative brain-based biomarkers.
Genetically engineered heat-resistant coral: An initial analysis of public opinion
Authors: Hobman Elizabeth V. , Mankad Aditi , Carter Lucy , Ruttley Chantale
Published: January 2022

Rising seawater temperatures are contributing to coral degradation in the Great Barrier Reef. Synthetic biology technologies offer the potential to enhance coral resilience to higher water temperatures. To explore what the public think of genetically engineered coral as a future solution, qualitative responses to an open-ended question in a survey of 1,148 of the Australian public were analysed. More respondents supported the technology (59%) than did not (11%). However, a considerable proportion indicated moderate support (29%). Participants commented about the (moral) right to interfere with nature and uncertainty regarding the consequences of implementing the technology. Participants also mentioned the need to take responsibility and act to save the reef, as well as the benefits likely to result from implementing the technology. Other themes included a desire for further testing and proof, more information, and tight regulation and controls when introducing the technology.
Neural correlates of local parallelism during naturalistic vision
Authors: Wilder John , Rezanejad Morteza , Dickinson Sven , Siddiqi Kaleem , Jepson Allan , Walther Dirk B.
Published: January 2022

Human observers can rapidly perceive complex real-world scenes. Grouping visual elements into meaningful units is an integral part of this process. Yet, so far, the neural underpinnings of perceptual grouping have only been studied with simple lab stimuli. We here uncover the neural mechanisms of one important perceptual grouping cue, local parallelism. Using a new, image-computable algorithm for detecting local symmetry in line drawings and photographs, we manipulated the local parallelism content of real-world scenes. We decoded scene categories from patterns of brain activity obtained via functional magnetic resonance imaging (fMRI) in 38 human observers while they viewed the manipulated scenes. Decoding was significantly more accurate for scenes containing strong local parallelism compared to weak local parallelism in the parahippocampal place area (PPA), indicating a central role of parallelism in scene perception. To investigate the origin of the parallelism signal we performed a model-based fMRI analysis of the public BOLD5000 dataset, looking for voxels whose activation time course matches that of the locally parallel content of the 4916 photographs viewed by the participants in the experiment. We found a strong relationship with average local symmetry in visual areas V1-4, PPA, and retrosplenial cortex (RSC). Notably, the parallelism-related signal peaked first in V4, suggesting V4 as the site for extracting paralleism from the visual input. We conclude that local parallelism is a perceptual grouping cue that influences neuronal activity throughout the visual hierarchy, presumably starting at V4. Parallelism plays a key role in the representation of scene categories in PPA.
Cognitive-behavioural pathways from pain to poor sleep quality and emotional distress in the general population: The indirect effect of sleep-related anxiety and sleep hygiene
Authors: Rakhimov Arman , Whibley Daniel , Tang Nicole K. Y.
Published: January 2022

Objectives

Pain can have a negative impact on sleep and emotional well-being. This study investigated whether this may be partly explained by maladaptive sleep-related cognitive and behavioural responses to pain, including heightened anxiety about sleep and suboptimal sleep hygiene.

Methods

This cross-sectional study used data from an online survey that collected information about pain (Brief Pain Inventory), sleep (Pittsburgh Sleep Quality Index; Sleep Hygiene Index; Anxiety and Preoccupation about Sleep Questionnaire) and emotional distress (PROMIS measures; Perceived Stress Scale). Structural equation modelling examined the tenability of a framework linking these factors.

Results

Of 468 survey respondents (mean age 39 years, 60% female), 29% reported pain (mean severity 1.12), most commonly in the spine or low back (28%). Pain severity correlated with poor sleep quality, poor sleep hygiene, anxiety about sleep and emotional distress. In the first structural equation model, indirect effects were identified between pain severity and sleep quality through anxiety about sleep (β = .08, p < .001) and sleep hygiene (β = .12, p < .001). In the second model, an indirect effect was identified between pain severity and emotional distress through sleep quality (β = .19, p < .01). Combining these models, indirect effects were identified between pain severity and emotional distress through anxiety about sleep, sleep hygiene and sleep quality.

Conclusions

This study provides data to support the tenability of a theoretically guided framework linking pain, sleep and emotional distress. If upheld by experimental and/or longitudinal study, this framework holds the potential to inform public health initiatives and more comprehensive pain assessment.
Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19
Authors: Lavilla Olleros Cristina , Ausín García Cristina , Bendala Estrada Alejandro David , Muñoz Ana , Wikman Jogersen Philip Erick , Fernández Cruz Ana , Giner Galvañ Vicente , Vargas Juan Antonio , Seguí Ripoll José Miguel , Rubio-Rivas Manuel , Miranda Godoy Rodrigo , Mérida Rodrigo Luis , Fonseca Aizpuru Eva , Arnalich Fernández Francisco , Artero Arturo , Loureiro Amigo Jose , García García Gema María , Corral Gudino Luis , Jiménez Torres Jose , Casas-Rojo José-Manuel , Millán Núñez-Cortés Jesús ,   On behalf of the SEMI-COVID-19 Network
Published: January 2022

Objective

To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses.

Methods

Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses.

Results

Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59–79] vs 73 years [IQR 61–83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91–2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75–0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32–1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71–0.95; p < .001 and OR 0.80 95% CI 0.65–0.97; p < .001) respectively.

Conclusion

There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.
Tanned leather of the paiche Arapaima gigas Schinz, 1822 (Arapaimidae) with extracts of vegetable origin to replace chromium salts
Authors: Cavali Jucilene , de Souza Maria Luiza Rodrigues , Silva de Oliveira Kanarski Patrícia , Coradini Melina Franco , Vieira Dantas Filho Jerônimo
Published: January 2022

With the intensification of fish farming, the amount of residues also increased. One of the by-products generated is leather. However, several factors influence its quality, among them, the types of tanning used. Paiche (Arapaima gigas) is the largest freshwater fish in the world, and therefore has great potential in the use of leather, in addition to being one of the most cultivated fish in the Rondônia state. The aimed was to evaluate the physicomechanical resistance, histological and morphological aspects in different directions of the fibers of the paiche to evaluate the tanning with chromium oxide and vegetable tannin. Paiches with an average weight of 12.0 kg were used, skins were made and tanned using chromium and vegetable tannin as techniques. After tanning, 20 specimens were removed in longitudinal, transverse and diagonal directions to the fish body, to determine resistance in dynamometer and leather for histological analysis, scanning electron microscopy and physical-chemical analysis. The average thickness of the specimens of the leathers ranged 1.79mm to 2.82mm, in addition, there was no interaction between the type of tanning agent and the directions obtained for strength, traction and elongation. Regarding the progressive tearing test, there was also no interaction effect. However, the defined factors had relevant differences for the maximum and average amount applied, and the leathers tanned with vegetable tannin expanded to larger dimensions 110.19 and 85.52 N. According to the images obtained by histology and scanning microscopy, they presented that in the longitudinal and transverse direction the collagen fibers are presented in layers parallel to the leather surface and in the diagonal direction the interlacing is more intense, that is, in addition to the overlapping layers intercalated thinner, close to the surface, fiber bundles can also be seen crossing each other. It is concluded that leathers tanned with vegetable tannin have less resistance than leathers tanned with chromium salts for traction to rupture and greater resistance to tear.
User experiences of a mobile phone-based health information and surveillance system (mHISS): A case of caregivers of children under-five in rural communities in Ghana
Authors: Acquah-Gyan Emmanuel , Acheampong Princess Ruhama , Mohammed Aliyu , Adjei Timothy Kwabena , Agyapong Emmanuel , Twumasi-Ankrah Sampson , Sylverken Augustina , Owusu Michael , Owusu-Dabo Ellis
Published: January 2022

Background

The rapid advancement of mobile technology has fueled the use of mobile devices for health interventions and for improving healthcare provision in underserved communities. Despite the potential of mHealth being used as a health information and surveillance tool, its scale-up has been challenging and, in most cases, unable to advance beyond the pilot stage of implementation. The purpose of this study was to explore user experiences of a mobile phone-based interactive voice response (IVR) system among caregivers of children under-five in rural communities in the Asante Akim North District of Ghana.

Methods

The study adopted an exploratory design. A convenience sampling technique was used to recruit 35 participants who had used an IVR system for at least six months for the study. About 11 in-depth interviews and three focus group discussions were conducted among participants using a semi-structured interview guide. Thematic content analysis was utilized for the analysis of data in this study.

Result

The system was found to be acceptable, and the attitude of caregivers towards the system was also positive. The study discovered that the mobile phone-based Health Information and Surveillance System (mHISS) was useful for improving access to healthcare, communicating with health professionals, served as a decision support system, and improved caregivers’ awareness about self-management of childhood illnesses. Poor network quality, unstable electricity power supply, and dropped/cut calls served as significant barriers to using the mHISS system.

Conclusion

The mHISS system was generally acceptable and could help improve access to healthcare and identify children with severe health conditions during outbreaks of diseases.
A 1 bp deletion in HACE1 causes ataxia in Norwegian elkhound, black
Authors: Bellamy Kim K. L. , Skedsmo Fredrik S. , Hultman Josefin , Arnet Ellen F. , Guttersrud Ole Albert , Skogmo Hege Kippenes , Thoresen Stein Istre , Espenes Arild , Jäderlund Karin Hultin , Lingaas Frode
Published: January 2022

A number of inherited ataxias is known in humans, with more than 250 loci implicated, most of which are included in human ataxia screening panels. Anecdotally, cases of ataxia in the Norwegian elkhound black have been known for the last 40 years. Affected puppies from three litters were clinically and neurologically examined, and postmortem samples were collected for morphological studies, including ultrastructural analyses. The puppies displayed vestibulocerebellar neurological signs and had degenerative histopathological alterations in cerebellum and brain stem. Three affected dogs, each from different litters, as well as both parents and one healthy littermate from each litter, were whole genome sequenced. Through variant calling we discovered a disease-associated 1 bp deletion in HACE1 (CFA12), resulting in a frameshift at codon 333 and a premature stop codon at codon 366. The perfect association combined with the predicted significant molecular effect, strongly suggest that we have found the causative mutation for Norwegian elkhound black ataxia. We have identified a novel candidate gene for ataxia where dogs can serve as a spontaneous model for improved understanding of ataxia, also in human.
Preliminary evaluation of alpha-emitting radioembolization in animal models of hepatocellular carcinoma
Authors: Du Yong , Cortez Angel , Josefsson Anders , Zarisfi Mohammadreza , Krimins Rebecca , Liapi Eleni , Nedrow Jessie R.
Published: January 2022

Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed cancer worldwide. Most patients with advanced disease are offered non-surgical palliative treatment options. This work explores the first alpha-particle emitting radioembolization for the treatment and monitoring of hepatic tumors. Furthermore, this works demonstrates the first in vivo simultaneous multiple-radionuclide SPECT-images of the complex decay chain of an [225Ac]Ac-labeled agent using a clinical SPECT system to monitor the temporal distribution. A DOTA chelator was modified with a lipophilic moiety and radiolabeled with the α-particle emitter Actinium-225. The resulting agent, [225Ac]Ac-DOTA-TDA, was emulsified in ethiodized oil and evaluated in vivo in mouse model and the VX2 rabbit technical model of liver cancer. SPECT imaging was performed to monitor distribution of the TAT agent and the free daughters. The [225Ac]Ac-DOTA-TDA emulsion was shown to retain within the HEP2G tumors and VX2 tumor, with minimal uptake within normal tissue. In the mouse model, significant improvements in overall survival were observed. SPECT-imaging was able to distinguish between the Actinium-225 agent (Francium-221) and the loss of the longer lived daughter, Bismuth-213. An α-particle emitting TARE agent is capable of targeting liver tumors with minimal accumulation in normal tissue, providing a potential therapeutic agent for the treatment of hepatocellular carcinoma as well as a variety of hepatic tumors. In addition, SPECT-imaging presented here supports the further development of imaging methodology and protocols that can be incorporated into the clinic to monitor Actinium-225-labeled agents.