bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to comment on “Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics”
Authors: Bovijn Jonas , Krebs Kristi , Chen Chia-Yen , Boxall Ruth , Censin Jenny C. , Ferreira Teresa , Pulit Sara L. , Glastonbury Craig A. , Laber Samantha , Millwood Iona Y. , Lin Kuang , Li Liming , Chen Zhengming , Milani Lili , Smith George Davey , Walters Robin G. , Mägi Reedik , Neale Benjamin M. , Lindgren Cecilia M. , Holmes Michael V.
Published: December 2021

Triangulation of evidence from clinical trials and human genetics suggests a potential excess risk of cardiovascular disease events arising from therapeutic inhibition of sclerostin.
Development of a Single-Cycle Infectious SARS-CoV-2 Virus Replicon Particle System for Use in Biosafety Level 2 Laboratories
Authors: Malicoat Johnny , Manivasagam Senthamizharasi , Zuñiga Sonia , Sola Isabel , McCabe Dianne , Rong Lijun , Perlman Stanley , Enjuanes Luis , Manicassamy Balaji
Published: December 2021

Due to the highly contagious nature of SARS-CoV-2 and the lack of immunity in the human population, research on SARS-CoV-2 has been restricted to biosafety level 3 laboratories. This has greatly limited participation of the broader scientific community in SARS-CoV-2 research and thus has hindered the development of vaccines and antiviral drugs.
Sporadic Dissemination of
tet
(X3) and
tet
(X6) Mediated by Highly Diverse Plasmidomes among Livestock-Associated Acinetobacter
Authors: Cheng Ying-Ying , Liu Yang , Chen Yong , Huang Fu-Man , Chen Rong-Chang , Xiao Yong-Hong , Zhou Kai
Published: December 2021

Recently identified plasmid-borne
tet
(X) genes have greatly challenged the efficiency of tigecycline, a last-resort antibiotic for severe infection, while the dissemination pattern of the plasmid-borne
tet
(X) genes remains unclear. In this study, we identified a clonal dissemination of
tet
(X3)-positive
A. towneri
isolates on a swine farm, while the
tet
(X6)-positive
A. towneri
strains mainly disseminated sporadically on the same farm.
A Novel Dibenzoxazepine Attenuates Intracellular Salmonella Typhimurium Oxidative Stress Resistance
Authors: Hsu Cheng-Yun , Wu Yi-Lun , Lin Hsueh-Chun , Lin Man-Yi , Chou Shih-Hsiu , Shiau Chung-Wai , Chiu Hao-Chieh
Published: December 2021

The incidence of diseases caused by pathogenic bacteria with resistance to common antibiotics is consistently increasing. In addition, Gram-negative bacteria are particularly difficult to treat with antibiotics, especially those that can invade and proliferate intracellularly.
Rare, disseminated Kaposi sarcoma in advanced HIV with high-burden pulmonary and skeletal involvement
Authors: Connolly Stephen P , McGrath Jonathan , Sui Jane , Muldoon Eavan G
Published: December 2021

We describe the case of a 30-year-old man who presented to our institution with hypoxia and widespread pulmonary infiltrates managed initially as COVID-19 before receiving a new diagnosis of HIV-associated Kaposi sarcoma (KS) with widespread pulmonary and skeletal involvement. Initial differential diagnoses includedPneumocystis jiroveciipneumonia, disseminated mycobacterial infection and bacillary angiomatosis. A bone marrow biopsy showed heavy infiltration by spindle cells, staining strongly positive for human herpes virus-8 (HHV-8) and CD34, suggesting symptomatic, disseminated KS as the unifying diagnosis. The patient commenced cytotoxic therapy with weekly paclitaxel, with a clinical and radiological response. To our knowledge, this case is among the most severe described in the literature, which we discuss, along with how COVID-19 initially hindered developing a therapeutic allegiance with the patient.
Self-reported provision of person-centred maternity care among providers in Kenya and Ghana: scale validation and examination of associated factors
Authors: Afulani Patience A , Aborigo Raymond A , Nutor Jerry John , Okiring Jaffer , Kuwolamo Irene , Ogolla Beryl A , Oboke Edwina N , Dorzie John Baptist K , Odiase Osamuedeme J , Steinauer Jody , Walker Dilys
Published: December 2021

Introduction

Person-centred maternity care (PCMC), which refers to care that is respectful and responsive to women’s preferences needs, and values, is core to high-quality maternal and child health. Provider-reported PCMC provision is a potentially valid means of assessing the extent of PCMC and contributing factors. Our objectives are to assess the psychometric properties of a provider-reported PCMC scale, and to examine levels and factors associated with PCMC provision.

Methods

We used data from two cross-sectional surveys with 236 maternity care providers from Ghana (n=150) and Kenya (n=86). Analysis included factor analysis to assess construct validity and Cronbach’s alpha to assess internal consistency of the scale; descriptive analysis to assess extent of PCMC and bivariate and multivariable linear regression to examine factors associated with PCMC.

Findings

The 9-item provider-reported PCMC scale has high construct validity and reliability representing a unidimensional scale with a Cronbach’s alpha of 0.72. The average standardised PCMC score for the combined sample was 66.8 (SD: 14.7). PCMC decreased with increasing report of stress and burnout. Compared with providers with no burnout, providers with burnout had lower average PCMC scores (β: −7.30, 95% CI:−11.19 to –3.40 for low burnout and β: −10.86, 95% CI: −17.21 to –4.51 for high burnout). Burnout accounted for over half of the effect of perceived stress on PCMC.

Conclusion

The provider PCMC scale is a valid and reliable measure of provider self-reported PCMC and highlights inadequate provision of PCMC in Kenya and Ghana. Provider burnout is a key driver of poor PCMC that needs to be addressed to improve PCMC.
Validation of the predictive accuracy of health-state utility values based on the Lloyd model for metastatic or recurrent breast cancer in Japan
Authors: Iwatani Tsuguo , Inoue Eisuke , Tsugawa Koichiro
Published: December 2021

Introduction

Although there is a lack of data on health-state utility values (HSUVs) for calculating quality-adjusted life-years in Japan, cost–utility analysis has been introduced by the Japanese government to inform decision making in the medical field since 2016.

Objectives

This study aimed to determine whether the Lloyd model which was a predictive model of HSUVs for metastatic breast cancer (MBC) patients in the UK can accurately predict actual HSUVs for Japanese patients with MBC.

Design

The prospective observational study followed by the validation study of the clinical predictive model.

Setting and participants

Forty-four Japanese patients with MBC were studied at 336 survey points.

Methods

This study consisted of two phases. In the first phase, we constructed a database of clinical data prospectively and HSUVs for Japanese patients with MBC to evaluate the predictive accuracy of HSUVs calculated using the Lloyd model. In the second phase, Bland-Altman analysis was used to determine how accurately predicted HSUVs (based on the Lloyd model) correlated with actual HSUVs obtained using the EuroQol 5-Dimension 5-Level questionnaire, a preference-based measure of HSUVs in patients with MBC.

Results

In the Bland-Altman analysis, the mean difference between HSUVs estimated by the Lloyd model and actual HSUVs, or systematic error, was −0.106. The precision was 0.165. The 95% limits of agreement ranged from −0.436 to 0.225. The t value was 4.6972, which was greater than the t value with 2 degrees of freedom at the 5% significance level (p=0.425).

Conclusions

There were acceptable degrees of fixed and proportional errors associated with the prediction of HSUVs based on the Lloyd model for Japanese patients with MBC. We recommend that sensitivity analysis be performed when conducting cost-effectiveness analyses with HSUVs calculated using the Lloyd model.
Retrospective observational study of characteristics of persons with amputations accessing International Committee of the Red Cross (ICRC) rehabilitation centres in five conflict and postconflict countries
Authors: Barth Cornelia Anne , Wladis Andreas , Blake Catherine , Bhandarkar Prashant , Aebischer Perone Sigiriya , O'Sullivan Cliona
Published: December 2021

Objectives

Limb amputation incidence is particularly high in fragile contexts due to conflict, accidents and poorly managed diabetes. The study aim was to analyse (1) demographic and amputation characteristics of persons with any type of acquired amputation (PwA) and (2) time between amputation and first access to rehabilitation in five conflict and postconflict countries.

Design

A retrospective, observational study analysing differences in demographic and clinical factors and time to access rehabilitation between users with traumatic and non-traumatic amputations.

Setting

Five countries with the highest numbers of PwA in the global International Committee of the Red Cross database (Afghanistan, Cambodia, Iraq, Myanmar, Sudan). Cleaned and merged data from 2009 to 2018 were aggregated by sex; age at amputation and registration; cause, combination and anatomical level of amputation(s); living environment.

Participants

All PwA newly attending rehabilitation.

Results

Data for 28 446 individuals were included (4 329 (15.2%) female). Most were traumatic amputations (73.4%, 20 890); of these, 48.6% (13 801) were conflict related. Average age at traumatic amputation for men and women was 26.9 and 24.1 years, respectively; for non-traumatic amputation it was 49.1 years and 45.9 years, respectively. Sex differences in age were statistically significant for traumatic and non-traumatic causes (p<0.001, p=0.003). Delay between amputation and rehabilitation was on average 8.2 years for those with traumatic amputation, significantly higher than an average 3 years for those with non-traumatic amputation (p<0.001).

Conclusions

Young age for traumatic and non-traumatic amputations indicates the devastating impact of war and fragile health systems on a society. Long delays between amputation and rehabilitation reveal the mismatch of needs and resources. For rehabilitation service providers in fragile settings, it is an enormous task to manage the diversity of PwA of various causes, age, sex and additional conditions. Improved collaboration between primary healthcare, surgical and rehabilitation services, a prioritisation of rehabilitation and increased resource provision are recommended to ensure adequate access to comprehensive rehabilitation care for PwA.
Impact and variability of social determinants of health on the transmission and outcomes of COVID-19 across the world: a systematic review protocol
Authors: Abedin Minhazul , Wahab Abrar , Rahman Farah Naz , Omi Fardina Rahman , Shareen Saadia , Rakhshanda Shagoofa , Islam Labida , Mayaboti Cinderella Akbar , Saha Uttam Kumar , Faruque Fazlay , Fletcher Lauren M , Mashreky Saidur
Published: December 2021

Introduction

The COVID-19 pandemic has exacerbated health inequalities across the globe, disproportionately affecting those with poor social determinants of health (SDOHs). It is imperative to understand how SDOH influences the transmission and outcomes (positive case, hospitalisation and mortality) of COVID-19. This systematic review will investigate the impact of a wide range of SDOHs across the globe on the transmission and outcomes of COVID-19.

Methods and analysis

This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. We will search three electronic bibliographical databases (MEDLINE via PubMed, Embase and Scopus), as well as the WHO COVID-19 Global Research on Coronavirus Disease database. We will consider observational studies that report statistical relationships between the SDOHs (as listed in PROGRESS-Plus and Healthy People 2020) and COVID-19 transmission and outcomes. There will be no limitation on the geographical location of publications. The quality of included observational studies will be assessed using a modified version of the Newcastle-Ottawa Scale. A narrative synthesis without meta-analysis reporting standards will be used to report the review findings.

Ethics and dissemination

This review will be based on published studies obtained from publicly available sources, and therefore, ethical approval is not required. We will publish the results of this review in a peer-reviewed journal, as well as present the study findings at a national conference.

PROSPERO registration number

CRD42021228818.
Primary care physician involvement during hospitalisation: a qualitative analysis of perspectives from frequently hospitalised patients
Authors: Rieger Erin Yildirim , Kushner Josef N S , Sriram Veena , Klein Abbie , Wiklund Lauren O , Meltzer David O , Tang Joyce W
Published: December 2021

Objective

To explore frequently hospitalised patients’ experiences and preferences related to primary care physician (PCP) involvement during hospitalisation across two care models.

Design

Qualitative study embedded within a randomised controlled trial. Semistructured interviews were conducted with patients. Transcripts were analysed using qualitative template analysis.

Setting

In the Comprehensive Care Programme (CCP) Study, in Illinois, USA, Medicare patients at increased risk of hospitalisation are randomly assigned to: (1) care by a CCP physician who serves as a PCP across both inpatient and outpatient settings or (2) care by a PCP as outpatient and by hospitalists as inpatients (standard care).

Participants

Twelve standard care and 12 CCP patients were interviewed.

Results

Themes included: (1) Positive attitude towards PCP; (2) Longitudinal continuity with PCP valued; (3) Patient preference for PCP involvement in hospital care; (4) Potential for in-depth involvement of PCP during hospitalisation often unrealised (involvement rare in standard care; in CCP, frequent interaction with PCP fostered patient involvement in decision making); and (5) PCP collaboration with hospital-based providers frequently absent (no interaction for standard care patients; CCP patients emphasising PCP’s role in interdisciplinary coordination).

Conclusion

Frequently hospitalised patients value PCP involvement in the hospital setting. CCP patients highlighted how an established relationship with their PCP improved interdisciplinary coordination and engagement with decision making. Inpatient–outpatient relational continuity may be an important component of programmes for frequently hospitalised patients. Opportunities for enhancing PCP involvement during hospitalisation should be considered.
Effectiveness of a digital dietary intervention program targeting young adults before parenthood: protocol for the PREPARED randomised controlled trial
Authors: Øverby Nina Cecilie , Medin Anine C , Valen Erlend Larsen , Salvesen Lorentz , Wills Andrew Keith , Engeset Dagrun , Vik Frøydis N , Hillesund Elisabet R
Published: December 2021

Introduction

The importance of preconception health for lifelong physical and mental health in the next generation has gained increasing recognition in recent years. Preconception paternal and maternal risk factors such as obesity and inadequate diet affect the metabolic and cardiovascular health of their offspring later in life. This highlights the importance of diet and dietary behaviour in the years before parenthood. In our project, PREPARED, we will evaluate the effectiveness of a digital intervention targeting young adults. Our primary aim is to improve participants’ preconception diet, and our secondary aim is to improve preconception quality of life and maternal and child perinatal outcomes.

Methods and analysis

We plan to recruit 7000 men and women individually, aged 20–35 years without children, to be randomised to an intervention or a control group. The intervention group will receive access to a digital resource for 6 months promoting a healthy diet for their health now, later in life and for the next generation. Follow-up is up to 20 years or until they have their first child. To evaluate intervention effects, we will collect dietary data (2×24-hour dietary recalls and a screener). For those participants for which birth ensues, we will link study data with data from the Medical Birth Registry of Norway on maternal and child perinatal outcomes.

Ethics and dissemination

The study is approved by the Regional Ethics Committee, the Norwegian Data Protection Service and our Faculty Ethical Committee (REC: 78104, NSD: 907212, FEC 20/10119). Participation is voluntary and all participants will provide informed consent. Participants can withdraw their consent without giving any reason. Findings will be communicated to the public through a project website and social media, and to professionals through conferences and peer-reviewed papers.

Trial registration number

ISRCTN44294662.
Role of post-trauma stress symptoms in the development of chronic musculoskeletal pain and disability: a protocol for a systematic review
Authors: Jadhakhan Ferozkhan , Evans David , Falla Deborah
Published: December 2021

Introduction

Post-traumatic stress symptoms (PTSS), pain and disability frequently co-occur following traumatic injuries. Although the coexistence of these symptoms is common, the relation between these symptoms and the impact on longer-term outcome remains poorly understood. This systematic review aims to determine the role of PTSS on the development of chronic pain and/or pain-related disability following musculoskeletal trauma.

Methods/analysis

This protocol is developed and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocol. The review will include studies that recruited individuals aged ≥16 years sustaining any traumatic event that resulted in one or more musculoskeletal injuries and where a recognised measure for the presence of PTSS symptoms, pain and disability using either validated questionnaires or symptom checklists was employed. The following citation databases MEDLINE, PsycINFO, EMBASE, CINAHL, ZETOC, Web of Science, PubMed and Google Scholar, as well as reference lists from key journals and grey literature, will be searched from inception to 31 November 2021. Two independent reviewers will search, screen studies, extract data and assess risk of bias. The relationship of PTSS, pain and pain-related disability by injury type and severity will be estimated with 95% CI. If possible, study results will be pooled into a meta-analysis. However, if heterogeneity between studies is high, data analyses will be presented descriptively. The overall quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation guidelines.

Ethics and dissemination

Ethical approval will not be required for this systematic review since only data from existing studies will be used. This review is expected to provide a better understanding of the factors associated with PTSS, pain and pain-related disability following musculoskeletal trauma, and help with the development of targeted therapeutic interventions. Results of this review will be disseminated in peer-reviewed publications and via national and international conferences.

PROSPERO registration number

CRD42021285243.
RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine
Authors: Long Tianyun , Abbasi Nazia , Hernandez Juan E , Li Yuxin , Sayed Ibrahim M , Ma Shengyun , Iemolo Attilio , Yee Brian A , Yeo Gene W , Telese Francesca , Ghosh Pradipta , Das Soumita , Huang Wendy Jia Men
Published: December 2021

Objective

Tuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in tumourigenesis. Commitment of intestinal progenitor cells to the tuft cell lineage requires Rho GTPase Cell Division Cycle 42 (CDC42), a Rho GTPase that acts downstream of the epidermal growth factor receptor and wingless-related integration site signalling cascades, and the master transcription factor POU class 2 homeobox 3 (POU2F3). This study investigates how this pathway is regulated by the DEAD box containing RNA binding protein DDX5 in vivo.

Design

We assessed the role of DDX5 in tuft cell specification and function in control and epithelial cell-specific Ddx5 knockout mice (DDX5ΔIEC) using transcriptomic approaches.

Results

DDX5ΔIEC mice harboured a loss of intestinal tuft cell populations, modified microbial repertoire, and altered susceptibilities to ileal inflammation and colonic tumourigenesis. Mechanistically, DDX5 promotes CDC42 protein synthesis through a post-transcriptional mechanism to license tuft cell specification. Importantly, the DDX5-CDC42 axis is parallel but distinct from the known interleukin-13 circuit implicated in tuft cell hyperplasia, and both pathways augment Pou2f3 expression in secretory lineage progenitors. In mature tuft cells, DDX5 not only promotes integrin signalling and microbial responses, it also represses gene programmes involved in membrane transport and lipid metabolism.

Conclusion

RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine.
Prognostic significance of tumour budding, tumour–stroma ratio and desmoplastic stromal reaction in gall bladder carcinoma
Authors: Goyal Surbhi , Banga Priyanka , Meena Nisha , Chauhan Geeta , Sakhuja Puja , Agarwal Anil Kumar
Published: December 2021

Aims and methods

The prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour–stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC.

Results

Higher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR <50% proved to be independent prognostic factors. The TBd score of stroma-rich tumour group (6.40±4.69) was significantly higher than that of stroma-poor group (2.77±3.79, p≤0.001). The TBd score of immature and intermediate DSR groups was significantly higher than that of mature group (p≤0.001 and p=0.002, respectively). There was a strong interobserver agreement for TBd score, TSR and type of DSR (Cohen’s Kappa=0.726 to 0.864, p≤0.001). Stroma-rich tumours were significantly associated with immature DSR and fibrotic DSR with high TSR (p≤0.001).

Conclusion

A high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.
Discoid lupus erythematosus skin lesion distribution and characteristics in Black patients: a retrospective cohort study
Authors: Joseph Adrienne K , Windsor Brandon , Hynan Linda S , Chong Benjamin F
Published: December 2021

Objective

Epidemiological studies have shown that discoid lupus erythematosus (DLE) has a higher incidence and prevalence in racial/ethnic minority groups, particularly Black individuals. The objective of this retrospective cohort study was to identify the differences in DLE lesion distribution and characteristics in Black individuals compared with non-Black individuals.

Methods

183 patients with DLE (112 Black patients and 71 non-Black patients) with a reported race/ethnicity and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores were included in this retrospective cohort study. Univariate analysis was performed to determine significant differences in demographic data, clinical characteristics, DLE lesion distribution and DLE lesion characteristics in Black and non-Black patients with DLE. Multivariable logistic regression was preformed to determine significant predictors of DLE lesion location and characteristics.

Results

Black patients with DLE had worse baseline CLASI damage scores compared with non-Black patients with DLE (median (IQR): 10.0 (6.0–14.5) vs 6.0 (3.0–10.0), p<0.001) and had 48.9 greater odds of dyspigmentation in any anatomical location (p<0.001). Black patients had 2.54 greater odds of having scalp involvement (p=0.015) and 1.97 greater odds of having ear involvement (p=0.032) compared with non-Black patients. Black patients also had greater odds of scalp dyspigmentation (OR=5.85, p<0.001), ear dyspigmentation (OR=2.89, p=0.001) and scarring alopecia (OR=3.00, p=0.001) compared with non-Black patients.

Conclusions

Signs of disease damage, particularly ear dyspigmentation, scalp dyspigmentation and scarring alopecia, can more frequently affect Black patients with DLE. Recognising differences in clinical presentation of DLE among Black patients can assist future efforts with understanding biological, cultural, psychosocial and systemic factors that influence DLE presentation and outcomes in Black patients and may guide clinicians when counselling Black patients.
Intracranial bruit: Charles Warlow’s challenge revisited
Authors: Larner Andrew J
Published: December 2021

Over 20 years ago, Charles Warlow, the founding editor ofPractical Neurology, offered a copy of his stroke textbook to anyone diagnosing an intracranial arteriovenous malformation by auscultation of the skull alone. This article examines the possible diagnostic value of intracranial bruit in terms of the 2×2 contingency table for diagnostic tests and recounts an historical case.
Risk factors for carotid plaque progression after optimising the risk factor treatment: substudy results of the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the carotid Bifurcation Plaque Study (ANTIQUE)
Authors: Školoudík David , Kešnerová Petra , Hrbáč Tomáš , Netuka David , Vomáčka Jaroslav , Langová Kateřina , Herzig Roman , Belšan Tomáš
Published: December 2021

Background and aim

Carotid plaque progression contributes to increasing stroke risk. The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the ‘treating arteries instead of risk factors’ strategy, that is, change in treatment depending on the progression of atherosclerosis.

Methods

The study participants who completed sonographic controls over the course of 3 years were enrolled to the analysis. Duplex sonography of cervical arteries was performed in 6-month intervals with measurement of carotid plaque thickness. Plaque thickness measurement error (σ) was set as 3 SD. Only evidently stable and progressive plaques (defined as plaque thickness difference between initial and final measurements of ˂σ and >2σ, respectively) were included to analysis. Univariate and multivariate logistic regression analysis was performed to identify factors influencing plaque progression.

Results

A total of 1391 patients (466 males, age 67.2±9.2 years) were enrolled in the study. Progressive plaque in at least one carotid artery was detected in 255 (18.3%) patients. Older age, male sex, greater plaque thickness, coronary heart disease, vascular surgery/stenting history and smoking were more frequently present in patients with progressive plaque (p˂0.05 in all cases). Multivariate logistic regression analysis identified only the plaque thickness (OR 1.850 for left side, 95% CI 1.398 to 2.449; and OR 1.376 for right side, 95% CI 1.070 to 1.770) as an independent factor influencing plaque progression.

Conclusion

Carotid plaque thickness corresponding to stenosis severity is the only independent risk factor for plaque thickness progression after optimising the prevention treatment.

Trial registration number

NCT02360137.
CT pectoralis muscle area is associated with DXA lean mass and correlates with emphysema progression in a tobacco-exposed cohort
Authors: O'Brien Michael Emmet , Zou Richard H , Hyre Nathan , Leader Joseph K , Fuhrman Carl R , Sciurba Frank C , Nouraie Mehdi , Bon Jessica
Published: December 2021

Introduction

Muscle loss is an important extrapulmonary manifestation of COPD. Dual energy X-ray absorptiometry (DXA) is the method of choice for body composition measurement but is not widely used for muscle mass evaluation. The pectoralis muscle area (PMA) is quantifiable by CT and predicts cross-sectional COPD-related morbidity. There are no studies that compare PMA with DXA measures or that evaluate longitudinal relationships between PMA and lung disease progression.

Methods

Participants from our longitudinal tobacco-exposed cohort had baseline and 6-year chest CT (n=259) and DXA (n=164) data. Emphysema was quantified by CT density histogram parenchymal scoring using the 15th percentile technique. Fat-free mass index (FFMI) and appendicular skeletal mass index (ASMI) were calculated from DXA measurements. Linear regression model relationships were reported using standardised coefficient (β) with 95% CI.

Results

PMA was more strongly associated with DXA measures than with body mass index (BMI) in both cross-sectional (FFMI: β=0.76 (95% CI 0.65 to 0.86), p<0.001; ASMI: β=0.76 (95% CI 0.66 to 0.86), p<0.001; BMI: β=0.36 (95% CI 0.25 to 0.47), p<0.001) and longitudinal (ΔFFMI: β=0.43 (95% CI 0.28 to 0.57), p<0.001; ΔASMI: β=0.42 (95% CI 0.27 to 0.57), p<0.001; ΔBMI: β=0.34 (95% CI 0.22 to 0.46), p<0.001) models. Six-year change in PMA was associated with 6-year change in emphysema (β=0.39 (95% CI 0.23 to 0.56), p<0.001) but not with 6-year change in airflow obstruction.

Conclusions

PMA is an accessible measure of muscle mass and may serve as a useful clinical surrogate for assessing skeletal muscle loss in smokers. Decreased PMA correlated with emphysema progression but not lung function decline, suggesting a difference in the pathophysiology driving emphysema, airflow obstruction and comorbidity risk.
Sensitivity of multi-PMT optical modules in Antarctic ice to supernova neutrinos of MeV energy
Authors: Lozano Mariscal C. J. , Classen L. , Unland Elorrieta M. A. , Kappes A.
Published: December 2021

New optical sensors with a segmented photosensitive area are being developed for the next generation of neutrino telescopes at the South Pole. In addition to increasing sensitivity to high-energy astrophysical neutrinos, we show that this will also lead to a significant improvement in sensitivity to MeV neutrinos, such as those produced in core-collapse supernovae (CCSN). These low-energy neutrinos can provide a detailed picture of the events after stellar core collapse, testing our understanding of these violent explosions. We present studies on the event-based detection of MeV neutrinos with a segmented sensor and, for the first time, the potential of a corresponding detector in the deep ice at the South Pole for the detection of extra-galactic CCSN. We find that exploiting temporal coincidences between signals in different photocathode segments, a $$27\ \mathrm {M}_{\odot }$$

27

M
⊙

progenitor mass CCSN can be detected up to a distance of 341 kpc with a false detection rate of $${0.01}\,\hbox {year}^{-1}$$

0.01

year

-
1

with a detector consisting of 10,000 sensors. Increasing the number of sensors to 20,000 and reducing the optical background by a factor of 70 expands the range such that a CCSN detection rate of 0.1 per year is achieved, while keeping the false detection rate at $${0.01}\,{\hbox {year}^{-1}}$$

0.01

year

-
1

.
Emergent universe revisited through the CSL theory
Authors: Bengochea Gabriel R. , Piccirilli María Pía , León Gabriel
Published: December 2021

In this work we analyze how the spectrum of primordial scalar perturbations is modified, within the emergent universe scenario, when a particular version of the Continuous Spontaneous Localization (CSL) model is incorporated as the generating mechanism of initial perturbations, providing also an explanation to the quantum-to-classical transition of such perturbations. On the other hand, a phase of super-inflation, prior to slow-roll inflation, is a characteristic feature of the emergent universe hypothesis. In recent works, it was shown that the super-inflation phase could generically induce a suppression of the temperature anisotropies of the CMB at large angular scales. We study here under what conditions the CSL maintains or modifies these characteristics of the emergent universe and their compatibility with the CMB observations.
Generalized compact star models with conformal symmetry
Authors: Jape J. W. , Maharaj S. D. , Sunzu J. M. , Mkenyeleye J. M.
Published: December 2021

We generate a new generalized regular charged anisotropic exact model that admits conformal symmetry in static spherically symmetric spacetime. Our model was examined for physical acceptability as realistic stellar models. The regularity is not violated, the energy conditions are satisfied, the physical forces balanced at equilibrium, the stability is satisfied via adiabatic index, and the surface red shift and mass–radius ratio are within the required bounds. Our conformal charged anisotropic exact solution contains models generated by Finch–Skea, Vaidya–Tikekar and Schwarzschild. Also, some recent charged or neutral and anisotropic or isotropic conformally symmetric models are found as special cases of our exact model. Our approach using a conformal symmetry provides a generalized geometric framework for studying compact objects.
Fluid sources in basement-hosted unconformity–uranium ore systems: tourmaline chemistry and boron isotopes from the Patterson Lake corridor deposits, Canada
Authors: Potter Eric G. , Kelly Colter J. , Davis William J. , Chi Guoxiang , Jiang Shao-Yong , Rabiei Morteza , McEwan Brian J.
Published: December 2021

The Patterson Lake corridor is a new uranium district located on the southwestern margin of the Athabasca Basin. Known resources extend almost 1 km below the unconformity in graphite- and sulfide-bearing shear zones within highly altered metamorphic rocks. Despite different host rocks and greater depths below the unconformity, alteration assemblages (chlorite, illite, kaolinite, tourmaline and hematite), ore grades and textures are typical of unconformity-related deposits. This alteration includes at least three generations of Mg-rich tourmaline (magnesio-foitite). The boron isotopic composition of magnesio-foitite varies with generation: the earliest generation, which is only observed in shallow samples from the Triple R deposit (Tur 1), contain the heaviest isotopic signature (

δ

11
B  ≈  19–26‰), whereas subsequent generations (Tur 2 and Tur 3) yield lighter and more homogeneous isotopic signatures (

δ

11
B  ≈  17.5–19.9‰). These results are consistent with precipitation from low-temperature, NaCl- and CaCl
2
-rich brine(s) derived from an isotopically heavy boron source (e.g. evaporated seawater) that interacted with tourmaline and silicates in the basement rocks and/or fluids derived from depth (with low

δ

11
B values). The lower

δ

11
B values in paragenetically later magnesio-foitite reflect greater contributions of basement-derived boron over time, whereas minor compositional variations reflect local metal sources (e.g. Cr, V, Ti) and evolving fluid chemistry (decreasing Na and Ca, increasing Mg) over time. The

δ

11
B and chemical variation in magnesio-foitite over time reinforce the strong interactions with basement rocks in these systems while supporting incursion of basinal brines well below the unconformity contact.

Supplementary material:
Complete analytical dataset including reference materials are available at
https://doi.org/10.6084/m9.figshare.c.5727555

Thematic collection:
This article is part of the Uranium Fluid Pathways collection available at:
https://www.lyellcollection.org/cc/uranium-fluid-pathways
Cloud Building Block Chip for Creating FPGA and ASIC Clouds
Authors: Doğan Atakan , Ebcioğlu Kemal
Published: December 2021

Hardware-accelerated cloud computing systems based on FPGA chips (FPGA cloud) or ASIC chips (ASIC cloud) have emerged as a new technology trend for power-efficient acceleration of various software applications. However, the operating systems and hypervisors currently used in cloud computing will lead to power, performance, and scalability problems in an exascale cloud computing environment. Consequently, the present study proposes a parallel hardware hypervisor system that is implemented entirely in special-purpose hardware, and that virtualizes application-specific multi-chip supercomputers, to enable virtual supercomputers to share available FPGA and ASIC resources in a cloud system. In addition to the virtualization of multi-chip supercomputers, the system’s other unique features include simultaneous migration of multiple communicating hardware tasks, and on-demand increase or decrease of hardware resources allocated to a virtual supercomputer. Partitioning the flat hardware design of the proposed hypervisor system into multiple partitions and applying the chip unioning technique to its partitions, the present study introduces a cloud building block chip that can be used to create FPGA or ASIC clouds as well. Single-chip and multi-chip verification studies have been done to verify the functional correctness of the hypervisor system, which consumes only a fraction of (10%) hardware resources.
Request, Coalesce, Serve, and Forget: Miss-Optimized Memory Systems for Bandwidth-Bound Cache-Unfriendly Applications on FPGAs
Authors: Asiatici Mikhail , Ienne Paolo
Published: December 2021

Applications such as large-scale sparse linear algebra and graph analytics are challenging to accelerate on FPGAs due to the short irregular memory accesses, resulting in low cache hit rates. Nonblocking caches reduce the bandwidth required by misses by requesting each cache line only once, even when there are multiple misses corresponding to it. However, such reuse mechanism is traditionally implemented using an associative lookup. This limits the number of misses that are considered for reuse to a few tens, at most. In this article, we present an efficient pipeline that can process and store thousands of outstanding misses in cuckoo hash tables in on-chip SRAM with minimal stalls. This brings the same bandwidth advantage as a larger cache for a fraction of the area budget, because outstanding misses do not need a data array, which can significantly speed up irregular memory-bound latency-insensitive applications. In addition, we extend nonblocking caches to generate variable-length bursts to memory, which increases the bandwidth delivered by DRAMs and their controllers. The resulting miss-optimized memory system provides up to 25% speedup with 24× area reduction on 15 large sparse matrix-vector multiplication benchmarks evaluated on an embedded and a datacenter FPGA system.
Deploying Multi-tenant FPGAs within Linux-based Cloud Infrastructure
Authors: Mbongue Joel Mandebi , Kwadjo Danielle Tchuinkou , Shuping Alex , Bobda Christophe
Published: December 2021

Cloud deployments now increasingly exploit Field-Programmable Gate Array (FPGA) accelerators as part of virtual instances. While cloud FPGAs are still essentially single-tenant, the growing demand for efficient hardware acceleration paves the way to FPGA multi-tenancy. It then becomes necessary to explore architectures, design flows, and resource management features that aim at exposing multi-tenant FPGAs to the cloud users. In this article, we discuss a hardware/software architecture that supports provisioning space-shared FPGAs in Kernel-based Virtual Machine (KVM) clouds. The proposed hardware/software architecture introduces an FPGA organization that improves hardware consolidation and support hardware elasticity with minimal data movement overhead. It also relies on VirtIO to decrease communication latency between hardware and software domains. Prototyping the proposed architecture with a Virtex UltraScale+ FPGA demonstrated near specification maximum frequency for on-chip data movement and high throughput in virtual instance access to hardware accelerators. We demonstrate similar performance compared to single-tenant deployment while increasing FPGA utilization, which is one of the goals of virtualization. Overall, our FPGA design achieved about 2× higher maximum frequency than the state of the art and a bandwidth reaching up to 28 Gbps on 32-bit data width.
Three Faces of Climate Justice
Authors: Dolšak Nives , Prakash Aseem
Published: December 2021

There is overwhelming consensus about the science of climate change. Climate politics, however, remains volatile, driven by perceptions of injustice, which motivate policy resistance and undermine policy legitimacy. We identify three types of injustice. The first pertains to the uneven exposure to climate change impacts across countries and communities within a country. Socially, politically, and economically disadvantaged communities that have contributed the least to the climate crisis tend to be affected the most. To address climate change and its impacts, countries and subnational units have enacted a range of policies. But even carefully designed mitigation and adaptation policies distribute costs (the second justice dimension) and benefits (the third justice dimension) unevenly across sectors and communities, often reproducing existing inequalities. Climate justice requires paying careful attention to who bears the costs and who gets the benefits of both climate inaction and action.
Simulated Study and Surface Passivation of Lithium Fluoride-Based Electron Contact for High-Efficiency Silicon Heterojunction Solar Cells
Authors: Khokhar Muhammad Quddamah , Hussain Shahzada Qamar , Chowdhury Sanchari , Zahid Muhammad Aleem , Pham Duy Phong , Cho Eun-Chel , Yi Junsin
Published: December 2021

Numerical simulation and experimental techniques were used to investigate lithium fluoride (LiFx) films as an electron extraction layer for the application of silicon heterojunction (SHJ) solar cells, with a focus on the paths toward excellent surface passivation and superior efficiency. The presence of a 7 nm thick hydrogenated intrinsic amorphous silicon (a-Si:H(i)) passivation layer along with thermally evaporated 4 nm thick LiFx resulted in outstanding passivation properties and suppresses the recombination of carriers. As a result, minority carrier lifetime (τ
eff) as well as implied open-circuit voltage (iVoc) reached up 933 μs and iVoc of 734 mV, accordingly at 120 °C annealing temperature. A detailed simulated study was performed for the complete LiFx based SHJ solar cells to achieve superior efficiency. Optimized performance of SHJ solar cells using a LiFx layer thickness of 4 nm with energy bandgap (Eg) of 10.9 eV and the work function of 3.9 eV was shown as: Voc = 745.7 mV, Jsc = 38.21 mA cm−2, FF = 82.17%, and η = 23.41%. Generally, our work offers an improved understanding of the passivation layer, electron extraction layer, and their combined effects on SHJ solar cells via simulation.
A wrinkle in time: circadian biology in pulmonary vascular health and disease
Authors: Bryant Andrew J. , Ebrahimi Elnaz , Nguyen Amy , Wolff Christopher A. , Gumz Michelle L. , Liu Andrew C. , Esser Karyn A.
Published: December 2021

An often overlooked element of pulmonary vascular disease is time. Cellular responses to time, which are regulated directly by the core circadian clock, have only recently been elucidated. Despite an extensive collection of data regarding the role of rhythmic contribution to disease pathogenesis (such as systemic hypertension, coronary artery, and renal disease), the roles of key circadian transcription factors in pulmonary hypertension remain understudied. This is despite a large degree of overlap in the pulmonary hypertension and circadian rhythm fields, not only including shared signaling pathways, but also cell-specific effects of the core clock that are known to result in both protective and adverse lung vessel changes. Therefore, the goal of this review is to summarize the current dialogue regarding common pathways in circadian biology, with a specific emphasis on its implications in the progression of pulmonary hypertension. In this work, we emphasize specific proteins involved in the regulation of the core molecular clock while noting the circadian cell-specific changes relevant to vascular remodeling. Finally, we apply this knowledge to the optimization of medical therapy, with a focus on sleep hygiene and the role of chronopharmacology in patients with this disease. In dissecting the unique relationship between time and cellular biology, we aim to provide valuable insight into the practical implications of considering time as a therapeutic variable. Armed with this information, physicians will be positioned to more efficiently use the full four dimensions of patient care, resulting in improved morbidity and mortality of pulmonary hypertension patients.
Low-dose fentanyl reduces pain perception, muscle sympathetic nerve activity responses, and blood pressure responses during the cold pressor test
Authors: Watso Joseph C. , Huang Mu , Belval Luke N. , Cimino Frank A. , Jarrard Caitlin P. , Hendrix Joseph M. , Hinojosa-Laborde Carmen , Crandall Craig G.
Published: December 2021

Our knowledge about how low-dose (analgesic) fentanyl affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose fentanyl influences human autonomic cardiovascular responses during painful stimuli in humans. Therefore, we tested the hypothesis that low-dose fentanyl reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-three adults (10 females/13 males; 27 ± 7 yr; 26 ± 3 kg·m−2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and 5 min after drug/placebo administration (75 μg fentanyl or saline). We compared pain perception (100-mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography, 11 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo timepoints) using paired, two-tailed t tests. Before drug/placebo administration, perceived pain ( P = 0.8287), ΔMSNA burst frequency ( P = 0.7587), and Δmean BP ( P = 0.8649) during the CPT were not different between trials. After the drug/placebo administration, fentanyl attenuated perceived pain (36 vs. 66 mm, P < 0.0001), ΔMSNA burst frequency (9 vs. 17 bursts/min, P = 0.0054), and Δmean BP (7 vs. 13 mmHg, P = 0.0174) during the CPT compared with placebo. Fentanyl-induced reductions in pain perception and Δmean BP were moderately related ( r = 0.40, P = 0.0641). These data provide valuable information regarding how low-dose fentanyl reduces autonomic cardiovascular responses during an experimental painful stimulus.
Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue
Authors: Henderson T. T. , Thorstensen J. R. , Morrison S. , Tucker M. G. , Kavanagh J. J.
Published: December 2021

Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.