bluuebunny/crossref_metadata_2025 huggingface dataset:
Isothermal Splitting of CO2 to CO Using Cobalt-Ferrite Redox Looping
Authors: Burra K. G. , Gupta A. K.
Published: October 2020

Rising atmospheric CO2 levels from significant imbalance between carbon emissions from fossil fuel utilization, especially for energy and chemicals, and natural carbon sequestration rates is known to drive-up the global temperatures and associated catastrophic climate changes, such as rising mean sea level, glacial melting, and extinction of ecosystems. Carbon capture and utilization techniques are necessary for transition from fossil fuel infrastructure to renewable energy resources to help delay the dangers of reaching to the point of positive feedback between carbon emissions and climate change which can drive terrestrial conditions to uninhabitable levels. CO2 captured from the atmosphere directly or from flue gases of a power plant can be recycled and transformed to CO and syngas for use as energy and value-added chemicals. Utilizing renewable energy resources to drive CO2 conversion to CO via thermochemical redox looping can provide a carbon negative renewable energy conversion pathway for sustainable energy production as well as value-added products. Substituted ferrites such as Co-ferrite, Mnferrite were found to be promising materials to aid the conversion of CO2 to CO at lower reduction temperatures. Furthermore, the conversion of these materials in the presence of Al2O3 provided hercynite cycling, which further lowered the reduction temperature. In this paper, Co-ferrite and Co-ferrite-alumina prepared via co-precipitation were investigated to understand their potential as oxygen carriers for CO2 conversion under isothermal redox looping. Isothermal reduction looping provided improved feasibility in redox conversion since it avoids the need for temperature swinging which improves thermal efficiency. These efforts alleviates the energy losses in heat recovery while also reducing thermal stresses on both the materials and the reactor. Lab-scale testing was carried out at 1673 K on these materials for extended periods and multiple cycles to gain insights into cyclic performance and the feasibility of sintering, which is a common issue in iron-oxide-based oxygen carriers. Cobalt doping provided with lowering of reduction temperature requirement at the cost of oxidation thermodynamic spontaneity that required increased oxidation temperature. At the concentrations examined, these opposing phenomenon made isothermal redox operation feasible by providing high CO yields comparable to oxygen carriers in the literature, which were operated at different temperatures for reduction and oxidation. Significantly high CO yields (∼ 750 μmol/g) were obtained from Co-ferrite isothermal redox looping. Co-ferrite-alumina provided lower CO yields compared to Co-ferrite. The oxygen storage was similar to those reported in the literature on isothermal H2O splitting, but with improved morphological stability at high temperature, especially compared to ferrite. This pathway of oxygen carrier development is considered suitable with further requirement in optimization for scaling of renewable CO2 conversion into valuable products.
Estimation of all six parameters of Johnson-Champoux-Allard-Lafarge model for acoustical porous materials from impedance tube measurements
Authors: Jaouen Luc , Gourdon Emmanuel , Glé Philippe
Published: October 2020

The open porosity of air-saturated acoustical porous materials is estimated from the low-frequency or high-frequency asymptotes of the real part of the dynamic bulk modulus. Combining this technique with the estimation of the static air-flow resistivity from the low-frequency asymptote of the imaginary part of the dynamic mass density and the analytical inversions of the remaining parameters from the dynamic mass density and bulk modulus [methods introduced by Panneton and Olny, J. Acoust. Soc. Am. 119(4), 2027–2040 (2006) and Olny and Panneton 123(2), 814–824 (2008)], this work estimates all six parameters of a Johnson-Champoux-Allard-Lafarge model from impedance tube measurements. A classical two-microphone impedance tube, as well as three- or four-microphone tubes, can be used for these measurements and estimations. Examples of applications and limits of the method are presented and a tool to estimate the open porosity and the static air-flow resistivity is made available online.
Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells
Authors: Gualdani Roberta , Seghers François , Yerna Xavier , Schakman Olivier , Tajeddine Nicolas , Achouri Younès , Tissir Fadel , Devuyst Olivier , Gailly Philippe
Published: October 2020

Fluid pressure in the proximal tubule activates TRPV4 to promote endocytosis and retention of albumin.
Heterogeneity and Diversity of
mcr-8
Genetic Context in Chicken-Associated Klebsiella pneumoniae
Authors: Wu Beibei , Wang Yao , Ling Zhuoren , Yu Zhuoling , Shen Zhangqi , Zhang Suxia , Wang Xiaoming
Published: October 2020

Increasing mobile colistin resistance, mediated by the
mcr
gene family, in
Enterobacteriaceae
has become a global concern. Among the 10 reported
mcr
genes,
mcr-8
was first identified in
Klebsiella pneumoniae
, which could cause severe infections with high mortality. Information about the prevalence and genetic context of
mcr-8
is still lacking. In this study, we found that
mcr-8
was present in 9.
Assessing Nanopore Sequencing for Clinical Diagnostics: a Comparison of Next-Generation Sequencing (NGS) Methods for Mycobacterium tuberculosis
Authors: Smith Carol , Halse Tanya A. , Shea Joseph , Modestil Herns , Fowler Randal C. , Musser Kimberlee A. , Escuyer Vincent , Lapierre Pascal
Published: October 2020

Next-generation sequencing technologies are being rapidly adopted as a tool of choice for diagnostic and outbreak investigation in public health laboratories. However, costs of operation and the need for specialized staff remain major hurdles for laboratories with limited resources for implementing these technologies. This project aimed to assess the feasibility of using Oxford Nanopore MinION whole-genome sequencing data of
Mycobacterium tuberculosis
isolates for species identification,
in silico
spoligotyping, detection of mutations associated with antimicrobial resistance (AMR) to accurately predict drug susceptibility profiles, and phylogenetic analysis to detect transmission between cases.
In Vitro
Profiling of Laninamivir-Resistant Substitutions in N3 to N9 Avian Influenza Virus Neuraminidase Subtypes and Their Association with
In Vivo
Susceptibility
Authors: Jeong Ju Hwan , Choi Won-Suk , Antigua Khristine Joy C. , Choi Young Ki , Govorkova Elena A. , Webby Richard J. , Baek Yun Hee , Song Min-Suk
Published: October 2020

The chemical structures of neuraminidase inhibitors (NAIs) possess similarities, but slight differences can result in variable susceptibility of avian influenza viruses (AIVs) carrying resistance-associated NA substitutions. Therefore, comprehensive susceptibility profiling of these substitutions in AIVs is critical for understanding the mechanism of antiviral resistance. In this study, we profiled resistance to the anti-influenza drug laninamivir in AIVs with substitutions known to impart resistance to other NAIs. We found 10 substitutions that conferred resistance to all four NAIs tested. On the other hand, we found that the remaining 26 NA substitutions were susceptible to at least one or more NAIs and showed for a small selection that
in vitro
data predicted
in vivo
behavior. Therefore, our findings highlight the usefulness of screening resistance markers in NA enzyme inhibition assays and animal models of AIV infections.
The Role of Neutrophils in Brucellosis
Authors: Moreno Edgardo , Barquero-Calvo Elías
Published: October 2020

Brucellosis is a bacterial disease of domestic animals and humans. The pathogenic ability ofBrucellaorganisms relies on their stealthy strategy and their capacity to replicate within host cells and to induce long-lasting infections.Brucellaorganisms barely induce neutrophil activation and survive within these leukocytes by resisting microbicidal mechanisms. Very fewBrucella-infected neutrophils are found in the target organs, except for the bone marrow, early in infection.
Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection
Authors: Steed Danielle Barrios , Wang Tiffany , Raheja Divyanshu , Waldman Alex D. , Babiker Ahmed , Dhere Tanvi , Kraft Colleen S. , Woodworth Michael H.
Published: October 2020

Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent
C. difficile
infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.
Four-Dimensional Characterization of the
Babesia divergens
Asexual Life Cycle, from the Trophozoite to the Multiparasite Stage
Authors: Conesa José Javier , Sevilla Elena , Terrón María Carmen , González Luis Miguel , Gray Jeremy , Pérez-Berná Ana J. , Carrascosa José L. , Pereiro Eva , Chichón Francisco Javier , Luque Daniel , Montero Estrella
Published: October 2020

Babesiosis is a disease caused by intraerythrocytic
Babesia
parasites, which possess many clinical features that are similar to those of malaria. This worldwide disease is increasing in frequency and geographical range and has a significant impact on human and animal health.
Babesia divergens
is one of the species responsible for human and cattle babesiosis causing death unless treated promptly. When
B. divergens
infects its vertebrate hosts, it reproduces asexually within red blood cells. During its asexual life cycle,
B. divergens
builds a population of numerous intraerythrocytic (IE) parasites of difficult interpretation. This complex population is largely unexplored, and we have therefore combined three- and four-dimensional imaging techniques to elucidate the origin, architecture, and kinetics of IE parasites. Unveiling the nature of these parasites has provided a vision of the
B. divergens
asexual cycle in unprecedented detail and is a key step to develop control strategies against babesiosis.
The Two-Component Response Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1 Control Antifungal Drug Resistance and Cell Wall Architecture of Candida auris
Authors: Shivarathri Raju , Jenull Sabrina , Stoiber Anton , Chauhan Manju , Mazumdar Rounik , Singh Ashutosh , Nogueira Filomena , Kuchler Karl , Chowdhary Anuradha , Chauhan Neeraj
Published: October 2020

Candida auris
is an emerging multidrug-resistant (MDR) fungal pathogen that presents a serious global threat to human health. The Centers for Disease Control and Prevention (CDC) have classified
C. auris
as an urgent threat to public health for the next decade due to its major clinical and economic impact and the lack of effective antifungal drugs and because of future projections concerning new
C. auris
infections. Importantly, the Global Antimicrobial Resistance Surveillance System (GLASS) has highlighted the need for more robust and efficacious global surveillance schemes enabling the identification and monitoring of antifungal resistance in
Candida
infections. Despite the clinical relevance of
C. auris
infections, our overall understanding of its pathophysiology and virulence, its response to human immune surveillance, and the molecular basis of multiple antifungal resistance remains in its infancy. Here, we show a marked phenotypic plasticity of
C. auris
clinical isolates. Further, we demonstrate critical roles of stress response mechanisms in regulating multidrug resistance and show that cell wall architecture and composition are key elements that determine antifungal drug susceptibilities. Our data promise new therapeutic options to treat drug-refractory
C. auris
infections.
Building a new platform to support public health emergency response in Africa: the AFENET Corps of Disease Detectives, 2018–2019
Authors: Masiira Ben , Antara Simon N , Kazoora Herbert B , Namusisi Olivia , Gombe Notion T , Magazani Alain N , Nguku Patrick M , Kazambu Ditu , Gitta Sheba N , Kihembo Christine , Sawadogo Bernard , Bogale Tatek A , Ohuabunwo Chima , Nsubuga Peter , Tshimanga Mufuta
Published: October 2020

Public health emergency (PHE) response in sub-Saharan Africa is constrained by inadequate skilled public health workforce and underfunding. Since 2005, the African Field Epidemiology Network (AFENET) has been supporting field epidemiology capacity development and innovative strategies are required to use this workforce. In 2018, AFENET launched a continental rapid response team: the AFENET Corps of Disease Detectives (ACoDD). ACoDD comprises field epidemiology graduates and residents and was established to support PHE response. Since 2018, AFENET has deployed the ACoDD to support response to several PHEs. The main challenges faced during ACoDD deployments were financing of operations, ACoDD safety and security, resistance to interventions and distrust of the responders by some communities. Our experience during these deployments showed that it was feasible to mobilise and deploy ACoDD within 48 hours. However, the sustainability of deployments will depend on establishing strong linkages with the employers of ACoDD members. PHEs are effectively controlled when there is a fast deployment and strong linkages between the stakeholders. There are ongoing efforts to strengthen PHE preparedness and response in sub-Saharan Africa. ACoDD members are a competent workforce that can effectively augment PHE response. ACoDD teams mentored front-line health workers and community health workers who are critical in PHE response. Public health emergence response in sub-Saharan Africa is constrained by inadequacies in a skilled workforce and underfunding. ACoDD can be utilised to overcome the challenges of accessing a skilled public health workforce. To improve health security in sub-Saharan Africa, more financing of PHE response is needed.
Gender-transformative programming with men and boys to improve sexual and reproductive health and rights: a systematic review of intervention studies
Authors: Ruane-McAteer Eimear , Gillespie Kathryn , Amin Avni , Aventin Áine , Robinson Martin , Hanratty Jennifer , Khosla Rajat , Lohan Maria
Published: October 2020

Background

Global health organisations advocate gender-transformative programming (which challenges gender inequalities) with men and boys to improve sexual and reproductive health and rights (SRHR) for all. We systematically review evidence for this approach.

Methods

We previously reported an evidence-and-gap map (http://srhr.org/masculinities/wbincome/) andsystematic review of reviewsof experimental intervention studies engaging men/boys in SRHR, identified through a Campbell Collaboration published protocol (https://doi.org/10.1002/CL2.203) without language restrictions between January 2007 and July 2018. Records for the current review of intervention studies were retrieved from those systematic reviews containing one or more gender-transformative intervention studies engaging men/boys. Data were extracted for intervention studies relating to each of the World Health Organization (WHO) SRHR outcomes. Promising programming characteristics, as well as underused strategies, were analysed with reference to the WHO definition of gender-transformative programming and an established behaviour change model, the COM-B model. Risk of bias was assessed usingCochrane Risk of Bias tools,RoB V.2.0 andRisk of Bias In Non-randomised Studies of Interventions.

Findings

From 509 eligible records, we synthesised 68 studies comprising 36 randomised controlled trials, n=56 417 participants, and 32 quasi-experimental studies, n=25 554 participants. Promising programming characteristics include: multicomponent activities of education, persuasion, modelling and enablement; multilevel programming that mobilises wider communities; targeting both men and women; and programmes of longer duration than three months. Six of the seven interventions evaluated more than once show efficacy. However, we identified a significant risk of bias in the overall available evidence. Important gaps in evidence relate to safe abortion and SRHR during disease outbreaks.

Conclusion

It is widely acknowledged by global organisations that the question is no longerwhetherto include boys and men in SRHR buthowto do so in ways that promote gender equality and health for all and are scientifically rigorous. This paper provides an evidence base to take this agenda for programming and research forward.
The socioeconomic dynamics of trends in female genital mutilation/cutting across Africa
Authors: Batyra Ewa , Coast Ernestina , Wilson Ben , Cetorelli Valeria
Published: October 2020

Background

The majority of women who undergo female genital mutilation/cutting (FGM/C) live in Africa. Although the UN Sustainable Development Goals call for intensified efforts to accelerate the abandonment of FGM/C, little is known about where in Africa the declines in prevalence have been fastest and whether changes in prevalence differ by women’s socioeconomic status.

Methods

We use data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys for 23 African countries, collected between 2002 and 2016, and covering 293 170 women. We reconstruct long-term cohort trends in FGM/C prevalence spanning 35 years, for women born between 1965 and 1999. We compute absolute and relative changes in FGM/C prevalence and differentials in prevalence by women’s education and urban-rural residence. We examine whether socioeconomic differences in FGM/C are converging or diverging.

Findings

FGM/C prevalence has declined fastest (in relative terms) in countries with lower initial prevalence, and more slowly in countries with higher initial prevalence. Although better-educated women and those living in urban areas tend to have lower prevalence, in some countries the opposite pattern is observed. Socioeconomic differentials in FGM/C have grown in the majority of countries, particularly in countries with moderate-to-higher overall prevalence.

Conclusions

The documented relationship between absolute and relative FGM/C prevalence rates suggests that in settings with higher initial prevalence, FGM/C practice is likely to be more entrenched and to change more slowly. There is substantial variation between countries in socioeconomic differentials in prevalence and their changes over time. As countries change from higher to lower overall prevalence, socioeconomic inequalities in FGM/C are increasing.
Clinical and financial burden of hospitalised community-acquired pneumonia in patients with selected underlying comorbidities in England
Authors: Campling James , Jones Dylan , Chalmers James , Jiang Qin , Vyse Andrew , Madhava Harish , Ellsbury Gillian , Rabe Adrian , Slack Mary
Published: October 2020

Background

Hospitalised pneumonia may have long-term clinical and financial impact in adult patients with underlying comorbidities.

Methods

We conducted a retrospective cohort study using the Hospital Episode Statistics (HES) database to determine the clinical and financial burden over 3 years of hospitalised community-acquired pneumonia (CAP) to England’s National Health Service (NHS). Subjects were adults with six underlying comorbidities (chronic heart disease (CHD); chronic kidney disease (CKD); chronic liver disease (CLD); chronic respiratory disease (CRD); diabetes mellitus (DM) and post bone marrow transplant (post-BMT)) with an inpatient admission in 2012/2013. Patients with CAP in 2013/2014 were followed for 3 years and compared with similarly aged, propensity score-matched adults with the same comorbidity without CAP.

Findings

The RR of hospital admissions increased after CAP, ranging from 1.08 (95% CI 1.04 to 1.12) for CKD to 1.38 (95% CI 1.35 to 1.40) for CRD. This increase was maintained for at least 2 years. Mean difference in hospital healthcare costs (£) was higher for CAP patients in 2013/2014; ranging from £1115 for DM to £8444 for BMT, and remained higher for 4/6 groups for 2 more years, ranging from £1907 (95% CI £1573 to £2240) for DM to £11 167 (95% CI £10 847 to £11 486) for CRD.) The OR for mortality was significantly higher for at least 3 years after CAP, ranging from 4.76 (95% CI 4.12 to 5.51, p<0.0001) for CLD to 7.50 (95%CI 4.71 to 11.92, p<0.0001) for BMT.

Interpretation

For patients with selected underlying comorbidities, healthcare utilisation, costs and mortality increase for at least 3 years after being hospitalised CAP.
Planning for success: overcoming challenges to recruitment and conduct of an open-label emergency department–led paediatric trial
Authors: Roper Louise , Lyttle Mark D , Gamble Carrol , Humphreys Amy , Messahel Shrouk , Lee Elizabeth D , Noblet Joanne , Hickey Helen , Rainford Naomi , Iyer Anand , Appleton Richard , Woolfall Kerry
Published: October 2020

Background

Key challenges to the successful conduct of The Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE) trial were identified at the pre-trial stage. These included practitioner anxieties about conducting research without prior consent (RWPC), inexperience in conducting an ED-led trial and use of a medication that was not usual ED practice. As part of an embedded study, we explored parent and practitioner experiences of recruitment, RWPC and conduct of the trial to inform the design and conduct of future ED-led trials.

Methods

A mixed-methods study within a trial involving (1) questionnaires and interviews with parents of randomised children, (2) interviews and focus groups with EcLiPSE practitioners and (3) audio-recorded trial discussions. We analysed data using thematic analysis and descriptive statistics as appropriate.

Results

A total of 143 parents (93 mothers, 39 fathers, 11 missing information) of randomised children completed a questionnaire and 30 (25 mothers, 5 fathers) were interviewed. We analysed 76 recorded trial recruitment discussions. Ten practitioners (4 medical, 6 nursing) were interviewed, 36 (16 medical, 20 nursing) participated in one of six focus groups. Challenges to the success of the trial were addressed by having a clinically relevant research question, pragmatic trial design, parent and practitioner support for EcLiPSE recruitment and research without prior consent processes, and practitioner motivation and strong leadership. Lack of leadership negatively affected practitioner engagement and recruitment. EcLiPSE completed on time, achieving its required sample size target.

Conclusions

Successful trial recruitment and conduct in a challenging ED-led trial was driven by trial design, recruitment experience, teamwork and leadership. Our study provides valuable insight from parents and practitioners to inform the design and conduct of future trials in this setting.
Management of cardiovascular emergencies during the COVID-19 pandemic
Authors: Choudhary Rahul , Gautam Dinesh , Mathur Rohit , Choudhary Dinesh
Published: October 2020

Background

It has been reported that patients attending the emergency department with other pathologies may not have received optimal medical care due to the lockdown measures in the early phase of the COVID-19 pandemic.

Methods

This was a retrospective study of patients presenting with cardiovascular emergencies to four tertiary regional emergency departments in western India during the government implementation of complete lockdown.

Results

25.0% of patients during the lockdown period and 17.4% of patients during the pre-lockdown period presented outside the window period (presentation after 12 hours of symptom onset) compared with only 6% during the pre-COVID period. In the pre-COVID period, 46.9% of patients with ST elevation myocardial infarction underwent emergent catheterisation, while in the pre-lockdown and lockdown periods, these values were 26.1% and 18.8%, respectively. The proportion of patients treated with intravenous thrombolytic therapy increased from 18.4% in the pre-COVID period to 32.3% in the post-lockdown period. Inhospital mortality for acute coronary syndrome (ACS) increased from 2.69% in the pre-COVID period to 7.27% in the post-lockdown period. There was also a significant decline in emergency admissions for non-ACS conditions, such as acute decompensated heart failure and high degree or complete atrioventricular block.

Conclusion

The COVID-19 pandemic has led to delays in patients seeking care for cardiac problems and also affected the use of optimum therapy in our institutions.
Gut microbiome stability and resilience: elucidating the response to perturbations
in order to modulate gut health
Authors: Fassarella Marina , Blaak Ellen E , Penders John , Nauta Arjen , Smidt Hauke , Zoetendal Erwin G
Published: October 2020

The human gut microbiome is a complex ecosystem, densely colonised by thousands of
microbial species. It varies among individuals and depends on host genotype and
environmental factors, such as diet and antibiotics. In this review, we focus on
stability and resilience as essential ecological characteristics of the gut microbiome
and its relevance for human health. Microbial diversity, metabolic flexibility,
functional redundancy, microbe–microbe and host–microbe interactions seem to be critical
for maintaining resilience. The equilibrium of the gut ecosystem can be disrupted by
perturbations, such as antibiotic therapy, causing significant decreases in functional
richness and microbial diversity as well as impacting metabolic health. As a
consequence, unbalanced states or even unhealthy stable states can develop, potentially
leading to or supporting diseases. Accordingly, strategies have been developed to
manipulate the gut microbiome in order to prevent or revert unhealthy states caused by
perturbations, including faecal microbiota transplantation, supplementation with
probiotics or non-digestible carbohydrates, and more extensive dietary modifications.
Nevertheless, an increasing number of studies has evidenced interindividual variability
in extent and direction of response to diet and perturbations, which has been attributed
to the unique characteristics of each individual’s microbiome. From a clinical,
translational perspective, the ability to improve resilience of the gut microbial
ecosystem prior to perturbations, or to restore its equilibrium afterwards, would offer
significant benefits. To be effective, this therapeutic approach will likely need a
personalised or subgroup-based understanding of individual genetics, diet, gut
microbiome and other environmental factors that might be involved.
Association between faecal occult bleeding and medicines prescribed for chronic disease: a data linkage study
Authors: Libby Gillian , Barnett Karen N , Fraser Callum G , Steele Robert J C
Published: October 2020

Aims

The presence of detectable faecal haemoglobin (f-Hb) has been shown to be associated with all-cause mortality and with death from a number of chronic diseases not known to cause gastrointestinal blood loss. This effect is independent of taking medicines that increase the risk of bleeding. To further investigate the association of f-Hb with chronic disease, the relationship between f-Hb and prescription of medicines for a variety of conditions was studied.

Methods

All subjects (134 192) who participated in guaiac faecal occult blood test (gFOBT) screening in Tayside, Scotland, between March 2000 and March 2016, were studied in a cross-sectional manner by linking their gFOBT result (abnormal or normal) with prescribing data at the time of the test.

Results

The screening participants with an abnormal gFOBT result were more likely to have been being prescribed medicines for heart disease, hypertension, diabetes and depression than those with a normal test result. This association persisted after adjustment for sex, age and deprivation (OR 1.35 (95%CI 1.23 to 1.48), 1.39 (1.27 to 1.52), 1.35 (1.15 to 1.58), 1.36 (1.16 to 1.59), all p<0.0001, for the four medicine categories, respectively).

Conclusions

The results of this study confer further substantial weight to the concept that detectable f-Hb is associated with a range of common chronic conditions that have a systemic inflammatory component; we speculate that f-Hb might have potential in identifying individuals who are high risk of developing chronic conditions or are at an early stage of disease.
Novel, non-invasive imaging approach to identify patients with advanced non-small cell lung cancer at risk of hyperprogressive disease with immune checkpoint blockade
Authors: Vaidya Pranjal , Bera Kaustav , Patil Pradnya D , Gupta Amit , Jain Prantesh , Alilou Mehdi , Khorrami Mohammadhadi , Velcheti Vamsidhar , Madabhushi Anant
Published: October 2020

Purpose

Hyperprogression is an atypical response pattern to immune checkpoint inhibition that has been described within non-small cell lung cancer (NSCLC). The paradoxical acceleration of tumor growth after immunotherapy has been associated with significantly shortened survival, and currently, there are no clinically validated biomarkers to identify patients at risk of hyperprogression.

Experimental design

A total of 109 patients with advanced NSCLC who underwent monotherapy with Programmed cell death protein-1 (PD1)/Programmed death-ligand-1 (PD-L1) inhibitors were included in the study. Using RECIST measurements, we divided the patients into responders (n=50) (complete/partial response or stable disease) and non-responders (n=59) (progressive disease). Tumor growth kinetics were used to further identify hyperprogressors (HPs, n=19) among non-responders. Patients were randomized into a training set (D1=30) and a test set (D2=79) with the essential caveat that HPs were evenly distributed among the two sets. A total of 198 radiomic textural patterns from within and around the target nodules and features relating to tortuosity of the nodule associated vasculature were extracted from the pretreatment CT scans.

Results

The random forest classifier using the top features associated with hyperprogression was able to distinguish between HP and other radiographical response patterns with an area under receiver operating curve of 0.85±0.06 in the training set (D1=30) and 0.96 in the validation set (D2=79). These features included one peritumoral texture feature from 5 to 10 mm outside the tumor and two nodule vessel-related tortuosity features. Kaplan-Meier survival curves showed a clear stratification between classifier predicted HPs versus non-HPs for overall survival (D2: HR=2.66, 95% CI 1.27 to 5.55; p=0.009).

Conclusions

Our study suggests that image-based radiomics markers extracted from baseline CTs of advanced NSCLC treated with PD-1/PD-L1 inhibitors may help identify patients at risk of hyperprogressions.
p50 suppresses cytotoxic T lymphocyte effector function to regulate tumor immune escape and response to immunotherapy
Authors: Lu Chunwan , Klement John D , Smith Alyssa D , Yang Dafeng , Waller Jennifer L , Browning Darren D , Munn David H , Liu Kebin
Published: October 2020

Background

NF-κB is a key link between inflammation and cancer. Previous studies of NF-κB have largely focused on tumor cells, and the intrinsic function of NF-κB in T cells in tumor development and response to immunotherapy is largely unknown. We aimed at testing the hypothesis that NF-κB1 (p50) activation in T cells underlies human colon cancer immune escape and human cancer non-response to anti-PD-1 immunotherapy.

Methods

We screened NF-κB activation in human colon carcinoma and used mouse models to determine p50 function in tumor cells and immune cells. RNA-Seq was used to identify p50 target genes. p50 binding to target gene promoters were determined by electrophoresis mobility shift assay and chromatin immunoprecipitation. A p50 activation score was generated from gene expression profiling and used to link p50 activation to T-cell activation and function pre-nivolumab and post-nivolumab immunotherapy in human patients with cancer.

Results

p50 is the dominant form of NF-κB that is highly activated in immune cells in the human colorectal carcinoma microenvironment and neighboring non-neoplastic colon epithelial cells. Tumor cell intrinsic p50 signaling and T-cell intrinsic p50 signaling exert opposing functions in tumor growth control in vivo. Deleting Nfkb1 in tumor cells increased whereas in T cells decreased tumor growth in preclinical mouse models. Gene expression profiling identified Gzmb as a p50 target in T cells. p50 binds directly to a previously uncharacterized κB sequence at the Gzmb promoter in T cells, resulting in repression of Gzmb expression in tumor-infiltrating cytotoxic T lymphocytes (CTLs) to induce a dysfunctional CTL phenotype to promote tumor immune escape. p50 activation is inversely correlated with both GZMB expression and T-cell tumor infiltration in human colorectal carcinoma. Furthermore, nivolumab immunotherapy decreased p50 activation and increased GZMB expression in human patients with melanoma.

Conclusions

Inflammation activates p50 that binds to the Gzmb promoter to repress granzyme B expression in T cells, resulting in CTL dysfunction to confer tumor immune escape and decreased response to anti-PD-1 immunotherapy.
Extreme diurnal temperature range and cardiovascular emergency hospitalisations in a Mediterranean region
Authors: Ponjoan Anna , Blanch Jordi , Alves-Cabratosa Lia , Martí Lluch Ruth , Comas-Cufí Marc , Parramon Dídac , García-Gil Maria M , Ramos Rafel , Petersen Irene
Published: October 2020

Objectives

The impact of extreme diurnal temperature range (DTR) on cardiovascular morbidity in Mediterranean regions remains uncertain. We aimed to analyse the impact of extreme low DTR (stable temperature) or high DTR (changeable temperature) on cardiovascular hospitalisations in Catalonia (Southern Europe).

Methods

We conducted a self-controlled case series study using whole-year data from the System for the Development of Research in Primary Care database and 153 weather stations from the Catalan Meteorological Service. The outcome was first emergency hospitalisation. Monthly DTR percentiles were used to define extreme DTR as low (DTR 95th percentile). We assessed two effects: same-day (1-day exposure, coinciding with the extreme DTR episode) and cumulative (3-day exposure, adding two subsequent days). Incidence rate ratios (IRR) were calculated adjusted by age, season and air pollution. Stratified analyses by gender, age or cardiovascular type and regions are provided.

Results

We computed 121 206 cardiovascular hospitalisations from 2006 to 2013. The IRR was 1.032 (95% CI 1.005 to 1.061) for same day and 1.024 (95% CI 1.006 to 1.042) for cumulative effects of extreme high DTR. The impact was significant for stroke and heart failure, but not for coronary heart disease. Conversely, extreme low DTR did not increase cardiovascular hospitalisations.

Conclusions

Extreme high DTR increased the incidence of cardiovascular hospitalisations, but not extreme low DTR. Same-day effects of extreme high DTR were stronger than cumulative effects. These findings contribute to better understand the impact of outdoor temperature on health, and to help defining public health strategies to mitigate such impact.
Employment and earnings trajectories before and after sickness absence due to major depressive disorder: a nationwide case–control study
Authors: Hakulinen Christian , Böckerman Petri , Pulkki-Råback Laura , Virtanen Marianna , Elovainio Marko
Published: October 2020

Objectives

To examine employment and earnings trajectories before and after the first sickness absence period due to major depressive disorder (MDD).

Methods

All individuals (n=158 813) in Finland who had a first sickness absence period (lasting longer than 9 days) due to MDD between 2005 and 2015 were matched with one randomly selected individual of the same age and gender with no history of MDD. Employment status and earnings were measured using register-based data annually from 2005 to 2015. Generalised estimating equations were used to examine the trajectories of employment and earnings before and after MDD diagnosis in men and women separately.

Results

Sickness absence due to MDD was associated with increased probability of non-employment during and after the year of the first sickness absence period. In men, but not in women, the probability of being employed was lower 5 years before the sickness absence period due to MDD. When compared with the individuals in the control group, men had around 34% and women 15% lower earnings 1 year, and 40% and 23%, respectively, 5 years, after the first sickness absence period due to MDD. More severe MDD and longer duration of sickness absence period were associated with lower probability of being employed.

Conclusions

Sickness absence due to MDD was associated with considerable reduction in employment and earnings losses. For men and individuals with more severe MDD, this reduction was before the first sickness period. This supports a reciprocal association between employment and earnings with MDD.
Regional anesthesia for scapular fracture surgery: an educational review of anatomy and techniques
Authors: Sonawane Kartik , Balavenkatasubramanian J , Dixit Hrudini , Tayi Harshitha , Goel Vipin Kumar
Published: October 2020

Scapular fractures are very rare, and those requiring surgical interventions are even rarer. Most scapula surgeries are done under general anesthesia with or without the regional anesthesia (RA) technique as an adjunct. Since scapular innervation is complicated, a thorough review of the relevant anatomy is warranted. In this RAPM educational article, we aimed to summarize the target nerves and blocks needed to optimize analgesia or even to provide surgical anesthesia for scapula surgeries. In this review, we are describing an algorithmic “identify-select-combine” approach, which enables the anesthesiologist to understand detailed innervation of the scapula and to obtain a procedure-specific RA technique. Procedure-specific RA would probably be the way forward for defining future RA practices.
Online popularity of JUUL and Puff Bars in the USA: 2019–2020
Authors: Dai Hongying , Hao Jianqiang
Published: October 2020

Background

The US Food and Drug Administration (FDA) announced a flavour ban on cartridge-based e-cigarettes in January 2020. It is unclear whether e-cigarette users will switch to disposable vaping products with a variety of kids-appealing flavours available.

Methods

We performed piece-wise regression and autoregressive integrated moving average (ARIMA) algorithms to compare the relative search volume (RSV) of JUUL and Puff Bar (a disposable vaping product) using the 1-year Google Trends data from 24 February 2019 to 20 February 2020, separated by three events that may have spurred changes in RSV for each product.

Results

The RSV for JUUL was relatively stable before Trump Administration announced plans to ban flavoured e-cigarettes. After that, the RSV for JUUL dropped sharply (rate of change=−8.8 per week) from 11 September 2019 to 17 October 2019 when JUUL Labs announced to halt online sales of some flavoured products, and the RSV resumed the decreasing trend after FDA announced enforcement policy of cartridge-based e-cigarettes on 2 January 2020. In comparison, the RSV for Puff Bar started to increase after 11 September 2019 with a low rate of change (0.6) until 17 October 2019. After that, the increase in RSV for Puff Bar accelerated. The RSV of puff bars surpassed that of JUUL during the week of 2 February 2020.

Conclusion

The popularity of Puff Bar on Google Search suggests that users may replace cartridge-based vaping products with disposable e-cigarettes in the circumvention of the partial flavour ban. Continuous surveillance and further assessment are needed to prevent potential loopholes in tobacco regulation.
Fault-Tolerant Maximal Local-Edge-Connectivity of Augmented Cubes
Authors: Zhai Liyang , Xu Liqiong , Yang Weihua
Published: October 2020

An interconnection network is usually modeled as a graph, in which vertices and edges correspond to processors and communication links, respectively. Connectivity is an important metric for fault tolerance of interconnection networks. A connected graph [Formula: see text] is said to be maximally local-edge-connected if each pair of vertices [Formula: see text] and [Formula: see text] of [Formula: see text] are connected by [Formula: see text] pairwise edge-disjoint paths. In this paper, we show that the [Formula: see text]-dimensional augmented cube [Formula: see text] is [Formula: see text]-edge-fault-tolerant maximally local-edge-connected and the bound [Formula: see text] is sharp; under the restricted condition that each vertex has at least three fault-free adjacent vertices, [Formula: see text] is [Formula: see text]-edge-fault-tolerant maximally local-edge-connected and the bound [Formula: see text] is sharp; and under the restricted condition that each vertex has at least [Formula: see text] fault-free adjacent vertices, [Formula: see text] is [Formula: see text]-edge-fault-tolerant maximally local-edge-connected. Furthermore, we show that a [Formula: see text]-regular graph [Formula: see text] is [Formula: see text]-fault-tolerant one-to-many maximally local-connected if [Formula: see text] does not contain [Formula: see text] and is super [Formula: see text]-vertex-connected of order 1, a [Formula: see text]-regular graph [Formula: see text] is [Formula: see text]-fault-tolerant one-to-many maximally local-connected if [Formula: see text] does not contain [Formula: see text] and is super [Formula: see text]-vertex-connected of order 1.
Connectivity and Diagnosability of Leaf-Sort Graphs
Authors: Wang Mujiangshan , Xiang Dong , Wang Shiying
Published: October 2020

The connectivity and diagnosability of a multiprocessor system and an interconnection network are two important research topics. The system and the network have an underlying topology, which is usually presented by a graph. As a topology structure of interconnection networks, the [Formula: see text]-dimensional leaf-sort graph [Formula: see text] has many good properties. In this paper, we prove that (a) [Formula: see text] is tightly [Formula: see text] super connected for odd [Formula: see text] and [Formula: see text], and tightly [Formula: see text] super connected for even [Formula: see text] and [Formula: see text]; (b) under the PMC model and MM[Formula: see text] model, the diagnosability [Formula: see text] for odd [Formula: see text] and [Formula: see text], and [Formula: see text] for even [Formula: see text] and [Formula: see text].
Structure and Substructure Connectivity of Hypercube-Like Networks
Authors: Lin Cheng-Kuan , Cheng Eddie , Lipták László
Published: October 2020

The connectivity of a graph [Formula: see text], [Formula: see text], is the minimum number of vertices whose removal disconnects [Formula: see text], and the value of [Formula: see text] can be determined using Menger’s theorem. It has long been one of the most important factors that characterize both graph reliability and fault tolerability. Two extensions to the classic notion of connectivity were introduced recently: structure connectivity and substructure connectivity. Let [Formula: see text] be isomorphic to any connected subgraph of [Formula: see text]. The [Formula: see text]-structure connectivity of [Formula: see text], denoted by [Formula: see text], is the cardinality of a minimum set [Formula: see text] of connected subgraphs in [Formula: see text] such that every element of [Formula: see text] is isomorphic to [Formula: see text], and the removal of [Formula: see text] disconnects [Formula: see text]. The [Formula: see text]-substructure connectivity of [Formula: see text], denoted by [Formula: see text], is the cardinality of a minimum set [Formula: see text] of connected subgraphs in [Formula: see text] whose removal disconnects [Formula: see text] and every element of [Formula: see text] is isomorphic to a connected subgraph of [Formula: see text]. The family of hypercube-like networks includes many well-defined network architectures, such as hypercubes, crossed cubes, twisted cubes, and so on. In this paper, both the structure and substructure connectivity of hypercube-like networks are studied with respect to the [Formula: see text]-star [Formula: see text] structure, [Formula: see text], and the [Formula: see text]-cycle [Formula: see text] structure. Moreover, we consider the relationships between these parameters and other concepts.
5-Shredders of Contraction-Critical 5-Connected Graphs
Authors: Qin Chengfu , Yang Weihua
Published: October 2020

Yoshimi Egawa [8] showed that a 5-connected graph G admits at most [Formula: see text] 5-shredders. In this paper we shown that a contraction-critical 5-connected graph G admits at most [Formula: see text] 5-shredders. Further we show that, for every contraction-critical 5-connected graph G, there is a contraction critical 5-connected graph [Formula: see text] such that G is a spanning subgraph of [Formula: see text] and [Formula: see text] admits at most [Formula: see text] 5-shredders.
A Brief Account on the Development and Future Research Directions of Connectivity Properties of Interconnection Networks
Authors: Cheng Eddie , Qiu Ke , Shen Zhizhang , Yang Weihua
Published: October 2020

Connectivity type measures form an important topic in graph theory. Such measures provide an important part of analyzing the vulnerability and resilience of interconnection networks. In this short commentary, we outline our perspective on the development of this topic with respect to interconnection networks.
Magic square and Dirac flavor neutrino mass matrix
Authors: Hyodo Yuta , Kitabayashi Teruyuki
Published: October 2020

The magic texture is one of the successful textures of the flavor neutrino mass matrix for the Majorana type neutrinos. The name “magic” is inspired by the nature of the magic square. We estimate the compatibility of the magic square with the Dirac, instead of the Majorana, flavor neutrino mass matrix. It turned out that some parts of the nature of the magic square are appeared approximately in the Dirac flavor neutrino mass matrix and the magic squares prefer the normal mass ordering rather than the inverted mass ordering for the Dirac neutrinos.
The Effects of Cannabis Use on the Development of Adolescents and Young Adults
Authors: Hall Wayne , Leung Janni , Lynskey Michael
Published: October 2020

This review summarizes evidence on the effects of cannabis use on the development of adolescents and young adults. It draws on epidemiological studies, neuroimaging studies, case-control studies, and twin and Mendelian randomization studies. The acute risks include psychiatric symptoms associated with the use of high THC (tetrahydrocannabinol) products and motor vehicle accidents. Daily cannabis use during adolescence is associated with cannabis dependence and poor cognitive function, which may affect educational attainment and occupational choice. Daily use of highly potent cannabis is associated with more severe psychological symptoms, such as psychoses, mania, and suicidality. There are more mixed findings on depressive symptoms, anxiety, and violence and debates about the interpretation of these associations. Legalization of adult cannabis use may increase cannabis use and dependence among adolescents and young adults. The regulation of cannabis after legalization needs to minimize adolescent uptake and cannabis-related adverse developmental outcomes.