bluuebunny/crossref_metadata_2025 huggingface dataset:
Leisure Sedentary Behavior Levels and Meeting Program Goals in a Community Lifestyle Intervention for Diabetes Prevention
Authors: Rockette-Wagner Bonny , Miller Rachel G. , Eaglehouse Yvonne L. , Arena Vincent C. , Kramer M. Kaye , Kriska Andrea M.
Published: December 2020

Background: The importance of leisure sedentary behavior (LSB) change in diabetes prevention efforts is not well known. This study examines the relationships between changes in self-reported LSB and the primary intervention goals (weight and moderate-intensity to vigorous-intensity physical activity [MVPA]) during a community-based translation of the Diabetes Prevention Program (the Group Lifestyle Balance Program). Methods: A total of 322 adults at risk for type 2 diabetes were recruited from 3 community centers, a worksite, and military site. Community and worksite participants were randomized to immediate or delayed-delivery (control) intervention. All military site participants (n = 99) received immediate intervention. Logistic and linear generalized estimating equations were used to determine associations between LSB changes and weight-related outcomes and MVPA. Results: Results were obtained for 259 (80.4%) participants. The LSB decreased after 6 and 12 months (mean [95% confidence interval]: −25.7 [−38.6 to −12.8] and −16.1 [−28.2 to −3.9] min/d; both P < .05). Each 20-minute reduction in LSB was associated with a 5% increase in odds of meeting the weight-loss goal (6 mo: odds ratio = 1.05 [1.002 to 1.102]; P = .042; adjusted model including MVPA), but LSB was not related to changes in reported MVPA minutes or MVPA goal achievement. Conclusion: Within the context of existing lifestyle intervention programs, reducing sedentary behavior has the potential to contribute to weight loss separately from reported MVPA improvement.
Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Authors: Larsen Mads Delbo , de Graaf Erik L. , Sonneveld Myrthe E. , Plomp H. Rosina , Nouta Jan , Hoepel Willianne , Chen Hung-Jen , Linty Federica , Visser Remco , Brinkhaus Maximilian , Šuštić Tonći , de Taeye Steven W. , Bentlage Arthur E. H. , Toivonen Suvi , Koeleman Carolien A. M. , Sainio Susanna , Kootstra Neeltje A. , Brouwer Philip J. M. , Geyer Chiara Elisabeth , Derksen Ninotska I. L. , Wolbink Gertjan , de Winther Menno , Sanders Rogier W. , van Gils Marit J. , de Bruin Sanne , Vlaar Alexander P. J. ,   Amsterdam UMC COVID-19,   biobank study group, Rispens Theo , den Dunnen Jeroen , Zaaijer Hans L. , Wuhrer Manfred , Ellen van der Schoot C. , Vidarsson Gestur , van Agtmael Michiel , Algera Anne Geke , van Baarle Frank , Bax Diane , van de Beek Diederik , Beudel Martijn , Bogaard Harm Jan , Bonta Peter I. , Bomers Marije , Bos Lieuwe , Botta Michela , de Bree Godelieve , Brouwer Matthijs C. , Brabander Justin , de Bruin Sanne , Bugiani Marianna , Bulle Esther , Chouchane Osoul , Cloherty Alex , Elbers Paul , Fleuren Lucas , Geerlings Suzanne , Geerts Bart , Geijtenbeek Theo , Girbes Armand , Goorhuis Bram , Grobusch Martin P. , Hafkamp Florianne , Hagens Laura , Hamann Jorg , Harris Vanessa , Hemke Robert , Hermans Sabine M. , Heunks Leo , Hollmann Markus W. , Horn Janneke , Hovius Joppe W. , de Jong Menno , Koning Rutger , van Mourik Niels , Nellen Jeaninne , Nossent Esther J. , Paulus Frederique , Peters Edgar , van der Poll Tom , Preckel Bennedikt , Prins Jan M. , Raasveld Jorinde , Rijnders Tom , Schinkel Michiel , Schultz Marcus , Schuurmans Alex R. , Sigaloff Kim , Smit Marry , Stijnis Cornelis S. , Stilma Willemke , Teunissen Charlotte , Thoral Patrick , Tsonas Anissa , van der Valk Marc , Veelo Denise , Vlaar Alexander P. J. , de Vries Heder , van Vugt Michèle , Wiersinga W. Joost , Wouters Dorien , Zwinderman A. H. (Koos)
Published: December 2020

A single sugar makes all the difference

Antibodies are divided into several classes based on their nonvariable tail (Fc) domains. These regions interact with disparate immune cell receptors and complement proteins to help instruct distinct immune responses. The Fc domain of immunoglobulin G (IgG) antibodies contains a conserved N-linked glycan at position 297. However, the particular glycan used at this position is highly variable. IgG lacking core fucosylation at this position initiates enhanced antibody-dependent cellular cytotoxicity by increased affinity to the Fc receptor FcRIIIa. Larsen
et al.
report that COVID-19 patients with severe symptoms have increased levels of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG afucosylation compared with patients with mild disease. These findings suggest that treatment of COVID-19 patients with fucosylated anti–SARS-CoV-2 antibodies may circumvent pathologies associated with severe COVID-19.

Science
, this issue p.
eabc8378
Autophagy protects tumors from T cell–mediated cytotoxicity via inhibition of TNFα-induced apoptosis
Authors: Young Tara M. , Reyes Claudia , Pasnikowski Elizabeth , Castanaro Carla , Wong Chung , Decker Corinne E. , Chiu Joyce , Song Hang , Wei Yi , Bai Yu , Zambrowicz Brian , Thurston Gavin , Daly Christopher
Published: December 2020

Autophagy reduces tumor cell sensitivity to T cell killing; thus, inhibiting autophagy may improve T cell–engaging therapies.
Activation of the Akt1-CREB pathway promotes
RNF146
expression to inhibit PARP1-mediated neuronal death
Authors: Kim Hyojung , Park Jisoo , Kang Hojin , Yun Seung Pil , Lee Yun-Song , Lee Yun-Il , Lee Yunjong
Published: December 2020

Akt1-activating compounds such as the polyphenol chlorogenic acid may prevent neuronal death in Parkinson’s disease.
Tissue-specific adrenergic regulation of the L-type Ca
2+
channel Ca
V
1.2
Authors: Man Kwun Nok Mimi , Bartels Peter , Horne Mary C. , Hell Johannes W.
Published: December 2020

Adrenergic stimulation induces differential phosphorylation of Ca
V
1.2 in brain and heart.
Neuroligin-2 as a central organizer of inhibitory synapses in health and disease
Authors: Ali Heba , Marth Lena , Krueger-Burg Dilja
Published: December 2020

The synaptic adhesion protein NLGN2 is integral to inhibitory neurotransmission and modulates behavior.
The ceramide fast track to puberty
Authors: Wong Wei
Published: December 2020

Diet-induced obesity triggers hypothalamic ceramide signaling that leads to precocious puberty in female rats.
Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis
Authors: Valafar Siavash J.
Published: December 2020

Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks.
Dissemination of Extended-Spectrum-β-Lactamase-Producing
Enterobacter cloacae
Complex from a Hospital to the Nearby Environment in Guadeloupe (French West Indies): ST114 Lineage Coding for a Successful IncHI2/ST1 Plasmid
Authors: Pot Matthieu , Guyomard-Rabenirina Stéphanie , Couvin David , Ducat Célia , Enouf Vincent , Ferdinand Séverine , Gruel Gaëlle , Malpote Edith , Talarmin Antoine , Breurec Sébastien , Reynaud Yann
Published: December 2020

Wastewater treatment plants are considered hot spots for antibiotic resistance. Most studies have addressed the impact on the aquatic environment, as water is an important source of anthropogenic pollutants.
Student-Scientist Curriculum: Integrating Inquiry-Based Research Experiences and Professional Development Activities into an Introductory Biology Laboratory Course
Authors: Spence Porché L. , Phillips Ruth S. , McAllister Akeem R. , White Sandra L. , Hollowell Gail P.
Published: December 2020

We designed a 16-week scaffolded student-scientist curriculum using inquiry-based research experiences integrated with professional development activities. This curriculum was implemented to teach undergraduate students enrolled in an introduction to biology course about enzyme activity, biochemical reactions, and alcohol fermentation. While working through the curriculum, students completed the entire scientific process by planning experiments, maintaining laboratory journals, analyzing and interpreting data, peer-reviewing research proposals, and producing and presenting a poster. The overall outcome was for students to complete a multiweek, collaborative, student-scientist project using
Saccharomyces cerevisiae
as the model organism. Student learning outcomes were evaluated using formative assessments (post-Research on the Integrated Science Curriculum survey and peer- and self-reflection worksheets) and summative assessments (pre/post assessments and assignment grades). Results indicated that more than 50% of the students scored 70% or higher on the collaborative student-scientist project, demonstrated several self-reported learning gains in scientific concepts and skills, and reported they would recommend this laboratory course to their peers. By providing the opportunity for students to carry out the entire scientific process, this curriculum enhanced their technical, analytical, and communication skills.
Injury patterns differ with age in male youth football: a four-season prospective study of 1111 time-loss injuries in an elite national academy
Authors: Wik Eirik Halvorsen , Lolli Lorenzo , Chamari Karim , Materne Olivier , Di Salvo Valter , Gregson Warren , Bahr Roald
Published: December 2020

Objectives

To describe age group patterns for injury incidence, severity and burden in elite male youth football.

Methods

Prospective cohort study capturing data on individual exposure and time-loss injuries from training and matches over four seasons (2016/2017 through 2019/2020) at a national football academy (U13–U18; age range: 11–18 years). Injury incidence was calculated as the number of injuries per 1000 hours, injury severity as the median number of days lost and injury burden as the number of days lost per 1000 hours.

Results

We included 301 players (591 player-seasons) and recorded 1111 time-loss injuries. Overall incidence was 12.0 per 1000 hours (95% CI 11.3 to 12.7) and burden was 255 days lost per 1000 hours (252 to 259). The mean incidence for overall injuries was higher in the older age groups (7.8 to 18.6 injuries per 1000 hours), while the greatest burden was observed in the U16 age group (425 days; 415 to 435). In older age groups, incidence and burden were higher for muscle injuries and lower for physis injuries. Incidence of joint sprains and bone stress injuries was greatest for players in the U16, U17 and U18 age groups, with the largest burden observed for U16 players. No clear age group trend was observed for fractures.

Conclusion

Injury patterns differed with age; tailoring prevention programmes may be possible.
(Not) talking about fertility: the role of digital technologies and health services in helping plan pregnancy. A qualitative study
Authors: French Rebecca S , Shawe Jill , Tilouche Nerissa , Earle Sarah , Grenfell Pippa
Published: December 2020

Aim

To explore how women and their partners navigate (pre)conception healthcare and the role of Natural Cycles fertility awareness technology in this process.

Methods

In-depth interviews with 24 cisgender women aged 24–43 years who had used Natural Cycles’ ‘Plan a Pregnancy’ mode, and six partners of Natural Cycles users, all cisgender men aged 30–39 years. Participants were recruited via direct messaging in the Natural Cycles app, social media and, for partners, snowball sampling. Purposive sampling was conducted to ensure diversity among participants. Interviews were audio-recorded and transcribed verbatim. An iterative, inductive approach was adopted for thematic data analysis.

Results

Natural Cycles helped most users better understand their menstrual cycles and fertility. Fertility awareness and preconception counselling with healthcare providers were uncommon. Women felt discussions about planning pregnancy in healthcare settings were often fraught with difficulties. They described not wanting to be an extra burden to overworked staff, being concerned that their worries about trying for pregnancy would be dismissed, or feeling staff did not have expertise in fertility awareness. Some women had shared their Natural Cycles data with healthcare professionals to demonstrate their menstrual cycle data or time of conception. However, it was not always clear to those not accessing services when they should seek further advice, for example, those using the app for longer time periods who had not yet conceived.

Conclusions

Digital technologies can provide information and support for those wanting to conceive. They should, however, complement care in statutory services, and be accompanied by greater investment in fertility awareness and preconception support.
Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia
Authors: Demb Joshua , Liu Lin , Murphy Caitlin C. , Doubeni Chyke A. , Martínez María Elena , Gupta Samir
Published: December 2020

Objective

Young-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC.

Design

Cohort study of US Veterans aged 18–49 years receiving Veterans Health Administration (VHA) care 1999–2016. IDA analytic cohort was created matching individuals without incident IDA to those with IDA 4:1 based on sex, birth year and first VHA visit date (n=239 000). We used this approach to also create a distinct haematochezia analytic cohort (n=653 740). Incident YCRC was ascertained via linkage to cancer registry and/or cause-specific mortality data. We computed cumulative incidence, risk difference (RD) and HRs using Cox models in each cohort.

Results

Five-year YCRC cumulative incidence was 0.45% among individuals with IDA versus 0.05% without IDA (RD: 0.39%, 95% CI: 0.33%–0.46%), corresponding to an HR of 10.81 (95% CI: 8.15–14.33). Comparing IDA versus no IDA, RD was 0.78% for men (95% CI: 0.64%–0.92%) and 0.08% for women (95% CI: 0.03%–0.13%), and RD increased by age from 0.14% for <30 years to 0.53% for 40–49 years. YCRC cumulative incidence was 0.33% among individuals with haematochezia versus 0.03% without haematochezia (RD: 0.30%, 95% CI: 0.26%–0.33%), corresponding to an HR of 10.66 (95% CI: 8.76–12.97). Comparing haematochezia versus no haematochezia, RD increased by age from 0.04% for <30 years to 0.43% for 40–49 years.

Conclusion

Colonoscopy should be strongly considered in adults aged <50 years with IDA or haematochezia without a clinically confirmed alternate source.
Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II
Authors: Blacher Mariana , Zimerman André , Engster Pedro H B , Grespan Eduardo , Polanczyk Carisi A , Rover Marciane M , Neto José A de Figueiredo , Danzmann Luiz C , Bertoldi Eduardo G , Simões Marcus Vinicius , Beck-da-Silva Luis , Biolo Andréia , Rohde Luis E
Published: December 2020

Objective

New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial.

Methods

The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient’s self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0–100).

Results

Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4–30) for class I vs 27.5 (11–49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248–1333) vs 778 (421–1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330–466) vs 351 m (286–408), p=0.028; overlap=64%). Among NYHA class I patients, 19%–34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%–10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14).

Conclusions

Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.
Meckel's Diverticulum in Adults: Seldom Suspected and Frequently Found
Authors: Friesen Chance S , Attard Thomas Mario , Cole Maria , Berry Jay G , Hall Matt
Published: December 2020

Meckel's diverticulum (MD) is a well-defined diagnosis in children presenting with either bleeding or obstruction. Although anecdotally adult patients may present with complications from MD, their presentation seems to be different, with a reported predominance of non-bleed-related presentations. Reports in this population, however, are limited, and little is known of the epidemiology of MD in older patients. We performed a retrospective analysis of the Agency of Healthcare Research and Quality National Inpatient Sample of all US hospital discharges from 2012 to 2016. We identified patients with a primary discharge diagnosis of MD. Data were abstracted as raw numbers and population weighted rates of discharge with age group, income level, length of stay (LOS) and hospital charges as additional information. On average, 2030 individuals were discharged annually; most (71.1%) were adults (>18 years). Although MD was predominant in males in all age groups, the gender ratio decreased with older age categories from 3.5:1.0 (1-17 years) to 1.6:1.0 (65-84 years). LOS averaged 5.3 days with no clear relationship to other parameters. Median income category, however, closely correlated (R2=0.9996) with diagnosis in older age categories. MD may be significantly more prevalent in adult patients than was previously understood. Differences in gender preponderance suggest that gender may influence the pattern of presentation. Diagnosis in older individuals is closely associated with income or socioeconomic status but not hospital charges or LOS.
Roux-En-Y Gastric Bypass and Sleeve Gastrectomy for Obesity-Associated Hypertension
Authors: Johnsen Erik Matthew , Sidhu Gursukhmandeep , Chen Jason , Moore Rachel , Le Jemtel Thierry , Samson Rohan
Published: December 2020

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) reduce blood pressure (BP) in obese patients with hypertension (HTN). We compared the effect of RYGB and SG on BP in obese patients with HTN at a large-volume, private bariatric surgery center using a propensity score analysis. The measurement and management of BP were exclusively left to the patient's provider without any involvement of Tulane investigators. At month 1, RYGB and SG equally decreased: (1) mean body weight: 12.7 vs 13.2 kg (p=not significant (NS)) (2) systolic/diastolic BP: 8.5/5.3 vs 8.0/4.2 mm Hg (p=NS) and (3) average number of antihypertensive medications from 1.5 to 0.8 and from 1.6 to 0.6 per patient (p=NS). From month 1 to 12, BP remained unchanged after RYGB but tended to increase from month 6 to 12 after SG. Remission of HTN occurred in 52% and 44% of patients after RYGB and SG. In contrast to the full effect of RYGB and SG on BP at 1 month, body weight decreases steadily over 12 months after RYGB and SG. In conclusion, early after surgery, RYGB and SG equally reduce BP in obese patients with HTN. Thereafter, RYGB has a more sustained effect on BP than SG.
Coexisting Psoriasis is Associated with An Increased Risk of Hospitalization for Patients with Inflammatory Bowel Disease: An Analysis of the National Inpatient Sample Database
Authors: Edigin Ehizogie , Asotibe Jennifer , Eseaton Precious Obehi , Busari Olukayode Ahmed , Achebe Ikechukwu , Kichloo Asim , Jamal Shakeel , Patel Axi
Published: December 2020

This study compares the odds of being admitted for inflammatory bowel disease (IBD) in patients with psoriasis compared with those without psoriasis alone. We also compared hospital outcomes of patients admitted primarily for IBD with and without a secondary diagnosis of psoriasis. Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database to search for hospitalizations of interest using International Classification of Diseases, 10th Revision codes. Multivariate logistic regression model was used to calculate the adjusted OR (AOR) of IBD being the principal diagnosis for hospitalizations with and without a secondary diagnosis of psoriasis. Multivariate logistic and linear regression analyses were used accordingly to compare outcomes of hospitalizations for IBD with and without secondary diagnosis of psoriasis. There were over 71 million discharges included in the combined 2016 and 2017 NIS database. Hospitalizations with a secondary diagnosis of psoriasis have an AOR of 2.66 (95% CI 2.40 to 2.96, p<0.0001) of IBD being the principal reason for hospitalization compared with hospitalizations without psoriasis as a secondary diagnosis. IBD hospitalizations with coexisting psoriasis have similar lengths of stay, hospital charges, need for blood transfusion, and similar likelihood of having a secondary discharge diagnosis of deep venous thrombosis, gastrointestinal bleed, sepsis, and acute kidney injury compared with those without coexisting psoriasis. Patients with coexisting psoriasis have almost three times the odds of being admitted for IBD compared with patients without psoriasis. Hospitalizations for IBD with coexisting psoriasis have similar hospital outcomes compared with those without coexisting psoriasis.
Initiation of immunotherapy with activated natural killer cells and anti-GD2 antibody dinutuximab prior to resection of primary neuroblastoma prolongs survival in mice
Authors: Zobel Michael John , Zamora Abigail K , Wu Hong-wei , Sun Jianping , Lascano Danny , Malvar Jemily , Wang Larry , Sheard Michael A , Seeger Robert C , Kim Eugene S
Published: December 2020

Background

Immunotherapy with anti-disialoganglioside dinutuximab has improved survival for children with high-risk neuroblastoma (NB) when given after induction chemotherapy and surgery. However, disease recurrence and resistance persist. Dinutuximab efficacy has not been evaluated when initiated before primary tumor removal. Using a surgical mouse model of human NB, we examined if initiating dinutuximab plus ex vivo-activated natural killer (aNK) cells before resection of the primary tumor improves survival.

Methods

In vitro, human NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc) were treated with dinutuximab and/or aNK cells and cytotoxicity was measured. In vivo, NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc, or COG-N-415x PDX) were injected into the kidney of NOD-scid gamma mice. Mice received eight intravenous infusions of aNK cells plus dinutuximab beginning either 12 days before or 2 days after resection of primary tumors. Tumors in control mice were treated by resection alone or with immunotherapy alone. Disease was quantified by bioluminescent imaging and survival was monitored. aNK cell infiltration into primary tumors was quantified by flow cytometry and immunohistochemistry at varying timepoints.

Results

In vitro, aNK cells and dinutuximab were more cytotoxic than either treatment alone. In vivo, treatment with aNK cells plus dinutuximab prior to resection of the primary tumor was most effective in limiting metastatic disease and prolonging survival. aNK cell infiltration into xenograft tumors was observed after 1 day and peaked at 5 days following injection.

Conclusion

Dinutuximab plus aNK cell immunotherapy initiated before resection of primary tumors decreases disease burden and prolongs survival in an experimental mouse model of NB. These findings support the clinical investigation of this treatment strategy during induction therapy in patients with high-risk NB.
Factors impacting health and well-being and the utilisation of supports among Australian doctors in medical specialty training
Authors: Abhary Sotoodeh , Botti Mari , Dhulia Anjali , Tham Christopher , Loh Erwin , Catford John
Published: December 2020

Purpose

To explore factors impacting the health and well-being of doctors undertaking various specialty training programs, and attitudes towards and utilisation of supports during their training. This is a subset of data from a larger study exploring experiences of doctors in Australian specialty training—a qualitative study of enablers, stressors and supports.

Methods

In this qualitative study, registrars in specialist training programmes in Australia were invited and interviewed between August 2015 and August 2016. Semistructured open-ended questions were used to explore topics of relevance to their workplace, training, support service utilisation and personal lives. Interviews were transcribed verbatim, deidentified and content and thematic analysis undertaken. Recruitment was ceased when data saturation was reached and no new themes emerged. Emerging key themes are reported in this study

Results

17 participants were recruited (including 1 Indigenous and 1 international medical graduate). A total of six specialty training programmes, across multiple states at various locations across Australia, were represented.

Common themes impacting health and well-being regarding workplace and training stressors were identified, including poor supervision, shiftwork and on-call, inability to take sick leave, bullying and harassment, college-related factors, examination preparation and work–life imbalance. Several of these were identified as having actual and perceived negative impacts on patient outcomes and safety.

The majority of participants underused existing supports and were unaware of the breadth of support services available to them. Barriers to accessing these services included concerns about their confidentiality and career repercussions.

Conclusions

This first Australian pilot study highlighted many stressors and enablers in the workplace, training and personal lives of registrars. The underutilisation and barriers to access of support services were discovered. Several multisystem strategies are required and discussed in this report to address these complex issues identified as affecting the health and well-being of junior doctors.
Covert medication and patient identity: placing the ethical analysis in a worldwide context
Authors: Pickering Neil John
Published: December 2020

In a recent JME article, Guidry-Grimes, Dean and Victor offer some signal and challenging insights into the ethical analysis of covert medication (in general) and in particular when administered via food. They warn of impacts on identity likely to emerge from using food in this way. In particular, they caution against allowing families to be involved in covert medication, in the light of their central role in sustaining identity. Their analysis has particular purchase in resource rich contexts and those contexts where individual identity is a central concern. But it is less clear that the article’s insights are relevant to other contexts. This article places the analysis of covert medication and identity in a wider context, arguing both that the focus on identity is equally significant when analysing potential alternatives to covert medication, such as coercion; and that the ethical analysis of covert medication offered by Guidry-Grimes, Dean and Victor lacks global applicability. It seems to lack application particularly in resource-poor contexts, and in cultures where identity and community are interconstituted.
COVID-19 ventilator rationing protocols: why we need to know more about the views of those with most to lose
Authors: Kerr Whitney , Schmidt Harald
Published: December 2020

Withholding or withdrawing life-saving ventilators can become necessary when resources are insufficient. With rising cases in many countries, and likely further peaks in the coming colder seasons, ventilator triage guidance remains a central part of the COVID-19 policy response. The dominant model in ventilator triage guidelines prioritises the ethical principles of saving the most lives and saving the most life-years. We sought to ascertain to what extent this focus aligns, or conflicts, with the preferences of disadvantaged minority populations. We conducted a bibliographical search of PubMed and Google Scholar and reviewed all ventilator rationing guidelines included in major recent systematic reviews, yielding 589 studies before screening. Post screening, we found six studies comprising a total of 10 591 participants, with 1247 from disadvantaged populations. Three studies reported findings stratified by race and age, two of which stratified by income. Studies included two to seven principles; all included ‘save the most lives’. Involvement of disadvantaged minority populations in eliciting preferences is very limited; few studies capture race and income. This is concerning, as despite relatively small numbers and framing effects there is an observable and plausible trend suggesting that disadvantaged groups worry that dominant principles reduce their chances of receiving a ventilator. To avoid compounding prior historical and structural disadvantage, policy makers need to engage more fully with these populations in designing and justifying ventilator rationing guidance and review their adequacy. Likewise, clinicians need to be aware that their implementation of dominant triage guidelines is viewed with higher levels of concern by minority populations.
Vertebroplasty and kyphoplasty in the USA from 2004 to 2017: national inpatient trends, regional variations, associated diagnoses, and outcomes
Authors: Hafezi-Nejad Nima , Bailey Christopher R , Solomon Alex J , Abou Areda Moustafa , Carrino John A , Khan Majid , Weiss Clifford R
Published: December 2020

Background

To explore the national inpatient trends, regional variations, associated diagnoses, and outcomes of vertebral augmentation (vertebroplasty and kyphoplasty) in the USA from 2004 to 2017.

Methods

Data from the National Inpatient Sample were used to study hospitalization records for percutaneous vertebroplasty and kyphoplasty. Longitudinal projections of trends and outcomes, including mortality, post-procedural complications, length of stay, disposition, and total hospital charges were analyzed.

Results

Following a period of decreased utilization from 2008 to 2012, hospitalizations for vertebroplasty and kyphoplasty plateaued after 2013. Total hospital charges and overall financial burden of hospitalizations for vertebroplasty and kyphoplasty increased to a peak of $1.9 billion (range $1.7–$2.2 billion) in 2017. Overall, 8% of procedures were performed in patients with a history of malignancy. In multivariable modeling, lung cancer (adjusted OR (aOR) 2.6 (range 1.4–5.1)) and prostate cancer (aOR 3.4 (range 1.2–9.4)) were associated with a higher risk of mortality. The New England region had the lowest frequency of routine disposition (14.1±1.1%) and the lowest average hospital charges ($47 885±$1351). In contrast, 34.0±0.8% had routine disposition in the West Central South region, and average hospital charges were as high as $99 836±$2259 in the Pacific region. The Mountain region had the lowest number of procedures (5365±272) and the highest mortality rate (1.2±0.3%).

Conclusion

National inpatient trends of vertebroplasty and kyphoplasty utilization remained stable after a period of decline from 2008 to 2012, while the financial burden of hospitalizations increased. Despite recent improvements in outcomes, significant regional variations persisted across the USA.
Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective
Authors: Zaidat Osama O , Ribo Marc , Mattle Heinrich Paul , Saver Jeffrey L , Bozorgchami Hormozd , Yoo Albert J , Ehm Alexandra , Kottenmeier Emilie , Cameron Heather L , Qadeer Rana A , Andersson Tommy
Published: December 2020

Background

First-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed.

Objective

To assess the economic impact of achieving complete or near complete reperfusion after the first pass.

Methods

Post hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c–3 was achieved, stratified into two groups: (1) mTICI 2c–3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK).

Results

Among patients who achieved mTICI 2c–3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0–2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24–33% reduction) and annual care (11–27% reduction) costs across all countries.

Conclusions

FPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.
DNA methylation is associated with airflow obstruction in patients living with HIV
Authors: Hernandez Cordero Ana I , Yang Chen Xi , Obeidat Maen , Yang Julia , MacIsaac Julie , McEwen Lisa , Lin David , Kobor Michael , Novak Richard , Hudson Fleur , Klinker Hartwig , Dharan Nila , Man SF Paul , Sin Don D , Kunisaki Ken , Leung Janice
Published: December 2020

Introduction

People living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.

Methods

Using blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV
1
, FEV
1
/FVC ratio and FEV
1
decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.

Results

Airflow obstruction as defined by a FEV
1
/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV
1
/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV
1
and FEV
1
/FVC, respectively. No positions were associated with FEV
1
decline.

Conclusion

A large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.
Impact of distance on postoperative follow-up in patients of pediatric surgery: a retrospective review
Authors: Wiebe Meagan E , Shawyer Anna C
Published: December 2020

Objective

Centralization of medical services in Canada has resulted in patients travelling long distances for healthcare, which may compromise their health. We hypothesized that children living farther from a children’s hospital were offered and attended fewer follow-up appointments.

Methods

We reviewed children less than 17 years of age referred to the general surgery clinic at a tertiary children’s hospital during a 2-year period who underwent surgery. Descriptive statistics were performed.

Results

We identified 723 patients. The majority were male (61%) with a median age of 7 years (range 18 days to16 years) and were from the major urban center (MUC) (56.3%). The median distance travelled to hospital for MUC patients was 8.9 km (range 0.9–22 km) vs 119.5 km (range 20.3–1950 km) for non-MUC patients. MUC children were offered more follow-up appointments (72.7% vs 60.8%, p<0.05). No significant differences existed in follow-up attendance rates (MUC 88.5% vs non-MUC 89.1%, p=0.84) or postoperative complications (9.8% vs 9.2%, p=0.78). There were no deaths.

Conclusions

Patients living farther from a hospital were offered fewer follow-up appointments, but attended an equivalent rate of follow-ups when offered one. Telemedicine and remote follow-up are underused approaches that can permit follow-up appointments while reducing associated travel time and expenses.
Lithogeochemical, isotopic, and U–Pb (zircon) age constraints on arc to rift magmatism, northwestern and central Avalon Terrane, Newfoundland, Canada: implications for local lithostratigraphy
Authors: Mills Andrea J. , Dunning Greg R. , Sandeman Hamish A.
Published: December 2020

The northwestern Avalon Terrane, Newfoundland, is underlain by Neoproterozoic rocks traditionally divided into older Love Cove Group, medial Connecting Point Group, and the unconformably overlying Musgravetown Group. New lithogeochemical, isotopic, and updated U–Pb (zircon) age data demand changes to stratigraphic nomenclature and maps and help constrain the tectonomagmatic evolution. U–Pb age constraints include 620 ± 2 Ma for the calc-alkaline Broad Island Group (former Love Cove Group); 605 ± 1.2 Ma for rhyolite from near Bull Arm (type area, Bull Arm Formation, lower Musgravetown Group); 589 ± 2.0 Ma for a schist from the Love Cove type locality; 568.7 ± 1.4 Ma for rhyolite of the Rocky Harbour Formation, upper Musgravetown Group; and 572 ± 2 Ma for Louil Hills granite. In light of these results, remnants of the main Avalonian arc are re-designated “Broad Island Group”, for the site of the dated 620 Ma tuff. The ca. 589 Ma schist from Love Cove is included in the Musgravetown Group and may be a tectonized equivalent of Bull Arm Formation. Our data outline a tectonomagmatic change from arc-dominated magmatism at ca. 620 Ma, to an extensional regime ca. 605–589 Ma, culminating in alkaline magmatism by ca. 572 Ma. εNdtvalues (t = 620–569 Ma) for felsic rocks range from 3.7 to 5.6 and yield TDMages consistent with derivation from a juvenile Neoproterozoic (878–730 Ma) basement. Mafic rocks exhibit a time-progressive increase in εNdt, indicating more juvenile mantle sources through time. Further delimitation of map units of the area await integrated lithostratigraphy, precise modern U–Pb geochronology, and lithogeochemistry.
Molecular hydrogen downregulates acute exhaustive exercise-induced skeletal muscle damage
Authors: Nogueira Jonatas E. , Amorim Mateus R. , Pinto Ana P. , da Rocha Alisson L. , da Silva Adelino S.R. , Branco Luiz G.S.
Published: December 2020

Physical exercise-induced skeletal muscle damage may be characterized by increased oxidative stress, inflammation, and apoptosis which may be beneficial when exercise is regular, but it is rather harmful when exercise is exhaustive and performed acutely by unaccustomed individuals. Molecular hydrogen (H2) has emerged as a potent antioxidant, anti-inflammatory, and anti-apoptotic agent, but its action on the deleterious effects of acute exhaustive exercise in muscle damage remain unknown. Therefore, we tested the hypothesis that H2 decreases acute exhaustive exercise-induced skeletal muscle damage of sedentary rats. Rats ran to exhaustion on a sealed treadmill inhaling an H2-containing mixture or the control gas. We measured oxidative stress (SOD, GSH, and TBARS), inflammatory (TNF-α, IL-1β, IL-6, IL-10, and NF-κB phosphorylation), and apoptotic (expression of caspase-3, Bcl-2, and HSP70) markers. Exercise caused no changes in SOD activity but increased TBARS levels. H2 caused increases in exercise-induced SOD activity and blunted exercise-induced increased TBARS levels. We observed exercise-induced TNF-α and IL-6 surges as well as NF-κB phosphorylation, which were blunted by H2. Exercise increased cleaved caspase-3 expression, and H2 reduced this response. In conclusion, H2 effectively downregulates muscle damage, reducing oxidative stress, inflammation, and apoptosis after acute exhaustive exercise performed by an unaccustomed organism.
Intracellular pH regulation and the acid delusion
Authors: Magder Sheldon , Magder Alexandr , Samoukovic Gordan
Published: December 2020

The hydrogen ion concentration ([H+]) in intracellular cytoplasmic fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation, failure to consider the roles played by differences in the concentration of strong ions (strong ion difference, SID), the conservation of mass, the principle of electrical neutrality, and that [H+] and bicarbonate ions [HCO3−] are dependent variables. This argument is based on the late Peter Stewart’s physical–chemical analysis of [H+] regulation reported in this journal nearly forty years ago (Stewart. 1983. Can. J. Physiol. Pharmacol. 61: 1444–1461. Doi: 10.1139/y83-207 ). We start by outlining the principles of Stewart’s analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominate regulation of [H+]. The primary strong ions are Na+, K+, and Cl−, and a few organic strong anions. The second independent variable, partial pressure of carbon dioxide (PCO2), can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles will potentially provide new insights into ICF pH regulation.
Genome sequence of Aspergillus flavus A7, a marine-derived fungus with antibacterial activity
Authors: Gao Yaru , Du Xinyang , Li Huanhuan , Wang Ying
Published: December 2020

Due to the specific properties of the marine environment, marine microorganisms have exclusive physicochemical characteristics that are different from those of terrestrial microorganisms, which can produce various secondary metabolites (SMs) with considerable structural diversity and biological activity. In this study, three strains of coepiphytic Aspergillus with potential antibacterial activities, A7 (Aspergillus flavus), B27 (Aspergillus flavipes), and R12 (Aspergillus sydowii), were isolated from the South China Sea. Via the Illumina MiSeq sequencing platform, the genomes of the three strains were sequenced, and genome comparison showed the highest diversity of the biosynthetic gene clusters (BGCs) in A7. In addition, a comparison of physiological and genomic characteristics between A7 and other A. flavus strains demonstrated the superior environmental adaptability of A7, which is apparently consistent with the genetic richness of BGCs. By assigning reads to known BGCs, putative BGCs were allocated in A7 that corresponded to various SMs, including naphthopyrone, pyranonigrin E, and cyclopiazonic acids. Based on gene homology analysis, we surmise that a region is involved in the biosynthesis of ustiloxin-like RiPPs, a less thoroughly studied SM in fungi. Our results provide genetic information for the investigation of marine Aspergillus spp., which may help to elucidate their chemical diversity and adaptive strategies.
Electroweak stability and discovery luminosities for new physics
Authors: Cankoçak Kerem , Demir Durmuş , Karahan Canan , Şen Sercan
Published: December 2020

What is the luminosity needed for discovering new physics if the electroweak scale is to remain stable? In this work we study this question, with the pertinent example of a real singlet scalar which couples to the Higgs field at the renormalizable level. Observing that the electroweak scale remains stable if the two scalars couple in a see-sawic fashion through a mass-degeneracy-driven unification linkup among quartic couplings at a given scale, we show by detailed simulation studies of the $$pp\rightarrow (\mathrm{singlet\ scalar}) \rightarrow Z Z \rightarrow 4\ell $$

p
p
→
(

singlet

scalar

)
→
Z
Z
→
4
ℓ

channel that the HL-LHC, which is expected to deliver an integrated luminosity of $$3~\mathrm{ab^{-1}}$$

3

ab

-
1

, has no significant excess of signal over the background in the 800–2000 GeV mass range. The FCC-hh, on the other hand, can discover scalars up to a mass of 870 GeV with an integrated luminosity $$20~\mathrm{ab^{-1}}$$

20

ab

-
1

. Observation at $$3\sigma $$

3
σ

(discovery at $$5\sigma $$

5
σ

) of a new scalar with a minimum mass 800 GeV requires at least $$2~\mathrm{ab^{-1}}$$

2

ab

-
1

($$5.2~\mathrm{ab^{-1}}$$

5.2

ab

-
1

) integrated luminosity, showing that the new physics that does not destabilize the electroweak scale is accessible only at very high luminosities, and can be tested already in the early stages of the FCC-hh operation period.
Altered EEG Oscillatory Brain Networks During Music-Listening in Major Depression
Authors: Zhu Yongjie , Wang Xiaoyu , Mathiak Klaus , Toiviainen Petri , Ristaniemi Tapani , Xu Jing , Chang Yi , Cong Fengyu
Published: December 2020

To examine the electrophysiological underpinnings of the functional networks involved in music listening, previous approaches based on spatial independent component analysis (ICA) have recently been used to ongoing electroencephalography (EEG) and magnetoencephalography (MEG). However, those studies focused on healthy subjects, and failed to examine the group-level comparisons during music listening. Here, we combined group-level spatial Fourier ICA with acoustic feature extraction, to enable group comparisons in frequency-specific brain networks of musical feature processing. It was then applied to healthy subjects and subjects with major depressive disorder (MDD). The music-induced oscillatory brain patterns were determined by permutation correlation analysis between individual time courses of Fourier-ICA components and musical features. We found that (1) three components, including a beta sensorimotor network, a beta auditory network and an alpha medial visual network, were involved in music processing among most healthy subjects; and that (2) one alpha lateral component located in the left angular gyrus was engaged in music perception in most individuals with MDD. The proposed method allowed the statistical group comparison, and we found that: (1) the alpha lateral component was activated more strongly in healthy subjects than in the MDD individuals, and that (2) the derived frequency-dependent networks of musical feature processing seemed to be altered in MDD participants compared to healthy subjects. The proposed pipeline appears to be valuable for studying disrupted brain oscillations in psychiatric disorders during naturalistic paradigms.