bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients
Authors: Divišová Petra , Šaňák Daniel , Václavík Jan , Král Michal , Hutyra Martin , Zapletalová Jana , Bártková Andrea , Franc David , Dorňák Tomáš , Veverka Tomáš , Táborský Miloš , Kaňovský Petr
Published: September 2020

Introduction:

In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients.

Methods:

The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification.

Results:

Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%,p= 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p= 0.011, OR: 6.125; 95% CI: 1.510–24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%,p= 1.000).

Conclusion:

AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.
Taiwan’s Successful COVID-19 Mitigation and Containment Strategy: Achieving Quasi Population Immunity
Authors: Chien Li-Chien , Beÿ Christian K. , Koenig Kristi L.
Published: September 2020

The authors describe Taiwan’s successful strategy in achieving control of coronavirus disease (COVID-19) without economic shutdown, despite the prediction that millions of infections would be imported from travelers returning from Chinese New Year celebrations in Mainland China in early 2020. As of September 2, 2020, Taiwan reports 489 cases, 7 deaths, and no locally acquired COVID-19 cases for the last 135 days (greater than 4 months) in its population of over 23.8 million people. Taiwan created quasi population immunity through the application of established public health principles. These non-pharmaceutical interventions, including public masking and social distancing, coupled with early and aggressive identification, isolation, and contact tracing to inhibit local transmission, represent a model for optimal public health management of COVID-19 and future emerging infectious diseases.
Ordinary care in extraordinary times
Authors: Patel S. , Gannon A. , Cryan M. , McDonnell N. , Rafiq S. , Adamis D. , Dolan C. , McCarthy G.
Published: September 2020

The Coronavirus Disease 2019 (COVID-19) has accounted for more than 25 000 cases in Ireland with approximately 28% of the clusters in nursing homes as of June 2020. The older population is the most vulnerable to serious complications from this illness and over 90% of deaths due to COVID-19 to date have been in patients over the age of 65. Continuing to provide routine care within nursing homes in these challenging times is an essential part of ensuring that presentations to hospitals for non-essential reasons are minimized. In this article, we describe a project being undertaken by a rural Psychiatry of Old Age Service in the northwest of Ireland. We aim to provide ordinary care in extraordinary times by using mobile tablets within the nursing homes and long-stay facilities in our region for remote video consultations during the COVID-19 crisis.
Vitamin D deficiency in schizophrenia implications for COVID-19 infection
Authors: Viani-Walsh D. , Kennedy-Williams S. , Taylor D. , Gaughran F. , Lally J.
Published: September 2020

Vitamin D deficiency is associated with an increased risk of acute respiratory infection. There is an excess of respiratory infections and deaths in schizophrenia, a condition where vitamin D deficiency is especially prevalent. This potentially offers a modifiable risk factor to reduce the risk for and the severity of respiratory infection in people with schizophrenia, although there is as yet no evidence regarding the risk of COVID-19. In this narrative review, we describe the prevalence of vitamin D deficiency in schizophrenia, report the research examining the relationship between vitamin D levels and COVID-19 and discuss the associations between vitamin D deficiency and respiratory infection, including its immunomodulatory mechanism of action.
Adapting an emotional regulation and social communication skills group programme to teletherapy, in response to the COVID-19 pandemic
Authors: MacEvilly D. , Brosnan G.
Published: September 2020

The COVID-19 pandemic created an unprecedented situation, whereby essential services within child and adolescent mental health services (CAMHS) were suspended. This created a need to modify regular methods of treatment at a rapid pace, to avoid cessation of clinical intervention and prevent potential regression in mental health. Eighteen children with moderate-to-severe mental health disorders and their parents were attending weekly group cognitive behaviour therapy-based sessions (‘The Secret Agent Society’ programme) when the Irish Department of Health suspended face-to-face intervention. This report describes how the group sessions were adapted to individualised, online therapeutic triads between each child, his/her parent and their clinician. Whilst internet technology has emerged as a promising solution to shortfalls in therapy services, in-depth exploration is needed to confirm the efficacy of telehealth for children attending CAMHS.
Social comparisons on social media: online appearance-related activity and body dissatisfaction in adolescent girls
Authors: Scully M. , Swords L. , Nixon E.
Published: September 2020

Introduction:

Adolescents’ engagement with online social networking platforms is advancing at an exponential rate and research is needed to investigate any impact on young users’ mental health. This study examined appearance-related activity (e.g. looking at photos of friends) on social media and body dissatisfaction among adolescent girls.

Methods:

Self-report measures of online appearance-related activity, social comparisons to female target groups, internalization of the thin ideal, body dissatisfaction, and self-esteem were administered to 210 girls (mean age = 15.16 years).

Results:

Body dissatisfaction was significantly related to (i) time spent engaged in social comparisons and (ii) upward social comparisons with various female targets while online. Evaluating oneself less favorably than the target group of close friends was most strongly associated with poorer body image appraisals. Serial multiple mediation analysis revealed that even after controlling for age and self-esteem, time spent engaged in social comparisons significantly mediated the relationship between online appearance-related activity and body dissatisfaction. This association was then further partially mediated by internalization of the thin ideal, which significantly mediated the relationship between time engaged in social comparisons and body dissatisfaction.

Discussion:

Results are discussed in terms of online social media platforms representing an additional appearance culture environment for adolescent girls. The effects of this on the mental health of vulnerable users and how future research should investigate protective factors that may buffer young girls from the adverse effects of social media are considered.
Continuity of solutions for the Δϕ-Laplacian operator
Authors: Cantizano Natalí A. , Salort Ariel M. , Spedaletti Juan F.
Published: September 2020

In this paper we give sufficient conditions to obtain continuity results of solutions for the so called ϕ-Laplacian Δϕ with respect to domain perturbations. We point out that this kind of results can be extended to a more general class of operators including, for instance, nonlocal nonstandard growth type operators.
The Non-Democratic Roots of Mass Education: Evidence from 200 Years
Authors: PAGLAYAN AGUSTINA S.
Published: September 2020

Because primary education is often conceptualized as a pro-poor redistributive policy, a common argument is that democratization increases its provision. But primary education can also serve the goals of autocrats, including redistribution, promoting loyalty, nation-building, and/or industrialization. To examine the relationship between democratization and education provision empirically, I leverage new datasets covering 109 countries and 200 years. Difference-in-differences and interrupted time series estimates find that, on average, democratization had no or little impact on primary school enrollment rates. When unpacking this average null result, I find that, consistent with median voter theories, democratizationcanlead to an expansion of primary schooling, but the key condition under which it does—when a majority lacked access to primary schooling before democratization—rarely holds. Around the world, state-controlled primary schooling emerged a century before democratization, and in three-fourths of countries that democratized, a majority already had access to primary education before democratization.
EARLY MEDIEVAL GARNET-INLAID METALWORK: A COMPARATIVE ANALYSIS OF DISC BROOCHES FROM EARLY WESSEX
Authors: Hamerow Helena , Shortland Andrew , Cameron Esther
Published: September 2020

Garnet-inlaid metalwork was an emblem of elite culture in the early medieval North Sea world. This study compares three Anglo-Saxon garnet-inlaid brooches that are exceptionally similar in design and appearance. All three date to the seventh century, a period that saw the emergence of leading families that used such deluxe dress items to enhance their political position. The central hypothesis explored here is that the brooches were produced by the same, or by closely linked, goldsmiths working under the patronage of such a family. Integrated analysis was conducted using microscopy, CT scans, XRF and XRD, in part to establish whether the garnets used came from the same or different sources.
Men and maternal health care utilization in India and in selected less-developed states: evidence from a large-scale survey 2015–16
Authors: Chattopadhyay Aparajita , Govil Dipti
Published: September 2020

Male involvement in maternal health care utilization is an important contributor to maternal health, especially in male-dominated societies. This study aimed to understand the variations and determinants of women’s antenatal care (ANC) utilization and institutional delivery in India and three socioeconomically less-developed states (Bihar, Madhya Pradesh and Uttar Pradesh) using NFHS-4 data (2015–16). Husband’s knowledge of pregnancy care and delivery, having a non-violent marital relationship and a respectful attitude towards his wife, better education and wealth, higher exposure to mass media and fewer children substantially enhanced the probability of him being present at his wife’s ANC visits. Furthermore, men’s presence at any ANC visit was shown to be an important factor influencing institutional delivery in India as a whole, as well as in the three less-developed states. The two major hurdles in maternal and child health care utilization in India were incorrect perception of ‘unnecessary’ maternal health care by families and high cost as reported by husbands. Furthermore, the proportion of husbands who received knowledge from health workers on maternal and child health was too low to achieve the maternal health SDGs by 2030. The dissemination of knowledge on maternal care among husbands, and encouraging their presence during antenatal care, may help secure better maternal health outcomes in India. It is imperative that the husband-involvement agenda is strengthened in India if the SDGs for maternal care are to be achieved.
Lithology could affect benthic communities living below boulders
Authors: Canessa M. , Bavestrello G. , Trainito E. , Navone A. , Cattaneo-Vietti R.
Published: September 2020

Structure and diversity of sessile zoobenthic assemblages seem to be driven not only by chemical-physical constraints and biological interactions but also by substrate lithology and its surface features. Nevertheless, broadly distributed crustose epilithic corallines could mask the role of substrate on animal settling. To evaluate the direct influence of different rocky substrates, occurrence and coverage of several sessile species, growing on the dark (i.e. coralline-free) face of sublittoral limestone and granite boulders were compared in the Tavolara MPA (Mediterranean Sea). The analysis of photographic samples demonstrated significant differences in terms of species composition and coverage, according to lithology. Moreover, limestone boulders were widely bare, while the cover per cent was almost total on granite. The leading cause of observed patterns could be the different level of dissolution of the two types of rocks, due to their different mineral composition and textural characteristics. Limestone has previously been shown to have higher dissolution compared with granite, and consequently, a more unstable surface. Our results suggest that, in dark habitats, the absence of the crustose coralline layer allows more rock dissolution and consequent lower stability of the limestone compared with granite, which, in turn, reduces the zoobenthos colonization.
Variations in prevalence and risk profiles for Common Mental Disorders amongst Rohingya, Chin and Kachin refugees from Myanmar
Authors: Tay Alvin Kuowei , Mohsin Mohammed , Hau Khat Mung , Badrudduza Mohammad , Balasundaram Susheela , Morgan Karen , Parthiban Nirmalatiban , Silove Derrick
Published: September 2020

Background

Large variations in prevalence rates of common mental disorder (CMD) amongst refugees and forcibly displaced populations have raised questions about the accuracy and value of epidemiological surveys in these cross-cultural settings. We examined the associations of sociodemographic indices, premigration traumatic events (TEs), postmigration living difficulties (PMLDs), and psychosocial disruptions based on the Adaptive Stress Index (ASI) in relation to CMD prevalence amongst the Rohingya, Chin and Kachin refugees originating from Myanmar and relocated to Malaysia.

Methods

Parallel epidemiological studies were conducted in areas where the three groups were concentrated in and around Malaysia (response rates: 80–83%).

Results

TE exposure, PMLDs and ASI were significantly associated with CMD prevalence in each group but the Rohingya recorded the highest exposure to all three of these former indices relative to Chin and Kachin (TE: mean = 11.1 v. 8.2 v. 11; PMLD: mean = 13.5 v. 7.4 v. 8.7; ASI: mean = 128.9 v. 32.1 v. 35.5). Multiple logistic regression analyses based on the pooled sample (n = 2058) controlling for gender and age, found that ethnic group membership, premigration TEs (16 or more TEs: OR, 2.00; 95% CI, 1.39–2.88; p < 0.001), PMLDs (10–15 PMLDs: OR, 4.19; 95% CI, 3.17–5.54; 16 or more PMLDs: OR, 7.23; 95% CI, 5.24–9.98; p < 0.001) and ASI score (ASI score 100 or greater: OR, 2.19; 95% CI, 1.46–3.30; p < 0.001) contributed to CMD.

Conclusions

Factors specific to each ethnic group and differences in the quantum of exposure to TEs, PMLDs and psychosocial disruptions appeared to account in large part for differences in prevalence rates of CMDs observed across these three groups.
Association of TLR3 (rs3775291) and IL-10 (rs1800871) gene polymorphisms with susceptibility to Hepatitis B infection: A meta-analysis
Authors: Ye Susu , Zhang Xinlei , Zhang Yu bao , Tian Xintao , Liu Ailing , Cui Changxing , Shi Lei , Xia Di
Published: September 2020

TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06–1.37), 1.28 (95% CI 1.04–1.56) and 1.20 (95% CI 1.06–1.37) and 1.40 (95% CI 1.07–1.83) in the allele model (C vs. T), dominant model (CC+CT vs. TT), recessive model (CC vs. CT+TT) and homozygous model (CC vs. TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (T vs. C), the pooled OR was 1.30 (95% CI 1.05–1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.
Transcriptional subtyping explains phenotypic variability in genetic subtypes of autism spectrum disorder
Authors: Trinh Sandy , Arnett Anne , Kurtz-Nelson Evangeline , Beighley Jennifer , Picoto Marta , Bernier Raphael
Published: September 2020

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes. Recent advances in transcriptomics have provided additional dimensions with which to refine genetic subtyping efforts. In the current study, we investigate phenotypic differences among transcriptional subtypes defined by neurobiological spatiotemporal co-expression patterns. Of the four transcriptional subtypes examined, participants with mutations to genes typically expressed highly in all brain regions prenatally, and those with differential postnatal cerebellar expression relative to other brain regions, showed lower cognitive and adaptive skills, higher severity of social communication deficits, and later acquisition of speech and motor milestones, compared to those with mutations to genes highly expressed during the postnatal period across brain regions. These findings suggest higher-order characterization of genetic subtypes based on neurobiological expression patterns may be a promising approach to parsing phenotypic heterogeneity among those with ASD and related neurodevelopmental disorders.
Reforming the Clergy Discipline Measure 2003 in Light of Parties’ Right to a Fair Trial
Authors: Baudon Raymond
Published: September 2020

When it was being introduced, there was a concern that the Clergy Discipline Measure 2003 would be a ‘complainant's charter’. While there was a marked increase in complaints after it came into force, this article argues that this concern was on the whole unfounded and as a result complainants have benefited. However, the Measure has had a damaging effect on respondents to the extent that reforming or replacing it is inevitable. It is argued that the current regime is potentially unfair in terms of common law and ECHR requirements to a fair trial. Therefore, any reform or replacement of the current regime must both be legally fair and also address its negative pastoral impact on respondents.
Effects of using machine translation to mediate the revision process of Korean university students’ academic writing
Authors: Lee Sangmin-Michelle , Briggs Neil
Published: September 2020

In recent years, marked gains in the accuracy of machine translation (MT) outputs have greatly increased its viability as a tool to support the efforts of English as a foreign language (EFL) students to write in English. This study examines error corrections made by 58 Korean university students by comparing their original L2 texts to that of MT outputs. Based on the results of the error analysis, the error types were categorized into 12 categories. Students were divided into three distinctive groups to determine differences among them according to the frequency of errors in their writing. The t-test results reveal that the numbers of errors significantly decreased in the revised versions for most of the error types among all groups. The results of the regression analysis also reveal a positive correlation relationship between the number of changes and the reduction of errors. However, the results also indicate that although all groups made error corrections at similar rates, students who less frequently committed errors in their L2 texts (higher language proficiency groups) generally tended to correct a higher proportion of errors. Based on the findings, pedagogical implications are discussed regarding how EFL teachers can effectively incorporate MT into the classroom.
Familial dilated cardiomyopathy with a novel LMNA mutation (p.R429C): a case report
Authors: Li Kun , Zhao Lanting , Zhang Ping
Published: September 2020

LMNA mutations cause a variety of inherited diseases referred to as laminopathies which are associated with a wide spectrum of disease phenotypes, ranging from skeletal muscle disease, pre-mature ageing, metabolic disorders, and cardiac abnormalities. We present a case of a 14-year-old boy with dilated cardiomyopathy induced by the LMNA mutation (p. R429C) and described its electrocardiogram and imaging features.
Implementing a healthy food retail policy: a mixed-methods investigation of change in stakeholders’ perspectives over time
Authors: Blake Miranda R , Boelsen-Robinson Tara , Hanna Lisa , Ryan Angela , Peeters Anna
Published: September 2020

Objectives:

To investigate (i) changes in stakeholder commitment and (ii) perceptions of the purpose, challenges and benefits of healthy food and beverage provision in community sports settings during the stepwise implementation of a healthy beverage policy.

Design:

Convergent, parallel, mixed-methods design complemented (i) repeat semi-structured interviews with council stakeholders (n 17 interviews, n 6 interviewees), with (ii) repeat quantitative stakeholder surveys measuring Commitment to Organisational Change; (iii) weekly sales data examining health behaviour and revenue effects (15 months pre-intervention; 14 months post-intervention); (iv) customer exit surveys (n 458); and (v) periodic photographic audits of beverage availability. Interviews were analysed inductively. Stakeholder surveys, sales data, customer surveys and audits were analysed descriptively.

Setting:

Four local government-owned sports and recreation centres in Melbourne, Australia, completed a 3-month trial to increase the availability of healthy beverages and decrease the availability of unhealthy beverages in food outlets.

Participants:

Interviews were conducted with council managers and those involved in implementation (September 2016–October 2017). Customers were surveyed (September–October 2017).

Results:

Interviews and surveys indicated that stakeholders’ commitment to policies varied such that, over time, optimism that changing beverage availability could increase the healthiness of customers’ purchases became more widespread among interviewees. Stakeholder focus generally progressed from anticipatory concern to solutions-focused discussions. Sales, audit and customer survey data supported interview findings.

Conclusions:

We found a general increase in optimism regarding policy outcomes over time during the implementation of a healthy beverage policy. Stepwise trials should be further explored as an engagement tool within community retail settings.
Malignant spinal cord compression (MSCC) presentation before and during Covid-19
Authors: Cameron Josie
Published: September 2020

Introduction:

Malignant spinal cord compression (MSCC) is a serious condition requiring urgent palliative radiotherapy to alleviate symptoms and avoid permanent paralysis. This audit compares the number of patients treated for MSCC before and during Covid-19, their treatment regimes and 30-day mortality rates to assess if the pandemic affected the treatment and the number of patients referred for palliative radiotherapy.

Methods:

A retrospective audit was performed (July–December 2019) and 101 patients were treated for MSCC, an average of 17 patients per month. A further audit was undertaken during Covid-19 (March–May 2020) and 36 patients were treated for MSCC, an average of 12 patients per month in this shorter cohort.

Results:

The results have demonstrated fewer patients presenting during the pandemic and this may be due to patients not wishing to utilise the National Health Service (NHS) during this time. It also highlighted the need to reduce the treatment duration to minimise hospital attendance and lessen the potential for exposure to Covid-19.

Conclusion:

Educating patients at risk of MSCC is essential and all cancer patients should be counselled on symptoms and what to do if they occur. Ensuring clinicians know the warning signs and the referral pathway for MSCC is also key to ensure early presentation and early referral for treatment.
Supporting Older Co-Resident Carers of Older People – The Impact of Care Act Implementation in Four Local Authorities in England
Authors: O’Rourke Gareth , Lloyd Liz , Bezzina Agnes , Cameron Ailsa , Jessiman Tricia , Smith Randall
Published: September 2020

The Care Act 2014 provides for ‘parity of esteem’ between people with social care needs and carers. This is achieved by extending the principles of prevention and wellbeing to carers; reinforcing carers’ right to an assessment; and setting national eligibility criteria for access to carer support services. This article reports on research that examined the impact of these changes on older co-resident carers of older people in four English local authorities. Findings are described in relation to four key themes: organisational arrangements and rationale; the aims of carer support and preventative services; design and delivery of carer assessment; and barriers to assessment and support. The findings of the research suggest that, despite the new statutory requirements, underlying contradictions and tensions in local authorities’ relationship with carers, and efforts to support them, remain unresolved.
Ethiopia’s Coffee-Growing Areas May Be Headed for the Hills
Authors: Tollera Mekonnen
Published: September 2020

New research suggests climate change may radically redefine the regions best suited to grow one of Ethiopia’s most valuable crops.
Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity
Authors: Lee Won Suk , Yang Hannah , Chon Hong Jae , Kim Chan
Published: September 2020

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, the tumor microenvironment (TME) functions as a formidable barrier that severely impairs the efficacy of ICIs. While the crosstalk between tumor vessels and immune cells determines the nature of anti-tumor immunity, it is skewed toward a destructive cycle in growing tumors. First, the disorganized tumor vessels hinder CD8+T cell trafficking into the TME, disable effector functions, and even kill T cells. Moreover, VEGF, the key driver of angiogenesis, interferes with the maturation of dendritic cells, thereby suppressing T cell priming, and VEGF also induces TOX-mediated exhaustion of CD8+T cells. Meanwhile, a variety of innate and adaptive immune cells contribute to the malformation of tumor vessels. Protumoral M2-like macrophages as well as TH2 and Treg cells secrete pro-angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. While CD8+T and CD4+TH1 cells suppress angiogenesis and induce vascular maturation by secreting IFN-γ, they are unable to infiltrate the TME due to malformed tumor vessels. These findings led to preclinical studies that demonstrated that simultaneous targeting of tumor vessels and immunity is a viable strategy to normalize aberrant vascular-immune crosstalk and potentiate cancer immunotherapy. Furthermore, this combination strategy has been evidently demonstrated through recent pivotal clinical trials, granted approval from FDA, and is now being used in patients with kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy and ICI is a valid therapeutic strategy that can enhance cancer immunity and will further expand the landscape of cancer treatment.
Lactobacillus fermentum promotes adipose tissue oxidative phosphorylation to protect against diet-induced obesity
Authors: Yoon Youngmin , Kim Gihyeon , Noh Myung-giun , Park Jeong-hyeon , Jang Mongjoo , Fang Sungsoon , Park Hansoo
Published: September 2020

The gut microbiota has pivotal roles in metabolic homeostasis and modulation of the intestinal environment. Notably, the administration ofLactobacillusspp. ameliorates diet-induced obesity in humans and mice. However, the mechanisms through whichLactobacillusspp. control host metabolic homeostasis remain unclear. Accordingly, in this study, we evaluated the physiological roles ofLactobacillus fermentumin controlling metabolic homeostasis in diet-induced obesity. Our results demonstrated thatL. fermentum-potentiated oxidative phosphorylation in adipose tissue, resulting in increased energy expenditure to protect against diet-induced obesity. Indeed, oral administration ofL. fermentumLM1016 markedly ameliorated glucose clearance and fatty liver in high-fat diet-fed mice. Moreover, administration ofL. fermentumLM1016 markedly decreased inflammation and increased oxidative phosphorylation in gonadal white adipose tissue, as demonstrated by transcriptome analysis. Finally, metabolome analysis showed that metabolites derived fromL. fermentumLM1016-attenuated adipocyte differentiation and inflammation in 3T3-L1 preadipocytes. These pronounced metabolic improvements suggested that the application ofL. fermentumLM1016 could have clinical applications for the treatment of metabolic syndromes, such as diet-induced obesity.
Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases
Authors: Jo Doo Sin , Park Na Yeon , Cho Dong-Hyung
Published: September 2020

In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular organelles, peroxisomes support key metabolic platforms for the oxidation of various fatty acids and regulate redox conditions. In addition, peroxisomes contribute to the biosynthesis of essential lipid molecules, such as bile acid, cholesterol, docosahexaenoic acid, and plasmalogen. Therefore, the quality control mechanisms that regulate peroxisome biogenesis and degradation are important for cellular homeostasis. Current evidence indicates that peroxisomal function is often reduced or dysregulated in various human disease conditions, such as neurodegenerative diseases. Here, we review the recent progress that has been made toward understanding the quality control systems that regulate peroxisomes and their pathological implications.
CYP2S1 is a synthetic lethal target in BRAFV600E-driven thyroid cancers
Authors: Li Yiqi , Su Xi , Feng Chao , Liu Siyu , Guan Haixia , Sun Yue , He Nongyue , Ji Meiju , Hou Peng
Published: September 2020

BRAFV600E is the most common genetic alteration and has become a major therapeutic target in thyroid cancers; however, intrinsic feedback mechanism limited clinical use of BRAFV600E specific inhibitors. Synthetic lethal is a kind of interaction between two genes, where only simultaneously perturbing both of the genes can lead to lethality. Here, we identified CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers. First, we found that CYP2S1 was highly expressed in papillary thyroid cancers (PTCs) compared to normal thyroid tissues, particularly in conventional PTCs (CPTCs) and tall-cell PTCs (TCPTCs), and its expression was positively associated with BRAFV600E mutation. CYP2S1 knockdown selectively inhibited cell proliferation, migration, invasion and tumorigenic potential in nude mice, and promoted cell apoptosis in BRAFV600E mutated thyroid cancer cells, but not in BRAF wild-type ones. Mechanistically, BRAFV600E-mediated MAPK/ERK cascade upregulated CYP2S1 expression by an AHR-dependent pathway, while CYP2S1 in turn enhanced transcriptional activity of AHR through its metabolites. This AHR/CYP2S1 feedback loop strongly amplified oncogenic role of BRAFV600E in thyroid cancer cells, thereby causing synthetic lethal interaction between CYP2S1 and BRAFV600E. Finally, we demonstrated CYP2S1 as a potential therapeutic target in both BRAFV600E-drived xenograft and transgenic mouse models by targetedly delivering CYP2S1-specific siRNA. Altogether, our data demonstrate CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers, and indicate that targeting CYP2S1 will provide a new therapeutic strategy for BRAFV600E mutated thyroid cancers.
The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study
Authors: Shahdad Shakeel , Patel Tulsi , Hindocha Annika , Cagney Neil , Mueller Jens-Dominik , Seoudi Noha , Morgan Claire , Din Ahmed
Published: September 2020

Introduction This study was conducted in light of the SARS-CoV-2 pandemic, which brought UK dentistry to a standstill. The market has seen a recent influx of unproven extraoral scavengers (EOSs), which claim to reduce the risk of particulate spread.

Aims To investigate the efficacy of a commercially available EOS device on contamination reduction during dental aerosol generating procedures (AGPs). The secondary aim was to investigate differences between open and closed dental operatories.

Method Dental procedures were simulated on a dental manikin using citric acid (10%) added to the water lines with universal indicating paper (UIP) placed in strategic locations in the operatory, on the clinician and assistant. Chromatic change related to settling of splatter containing citric acid on the UIP was analysed to calculate percentage intensity of splatter contamination.

Results EOSs resulted in 20% reduction in frequency and 75% reduction in mean intensity of contamination of operatory sites. There was a 33% and 76% reduction in mean intensity contamination for clinician and assistant, respectively. Use of rubber dam and four-handed dentistry resulted in further reduction.

Discussion This exploratory study demonstrates contamination by splatter in a simulated dental setting. The concern in dentistry regarding aerosol requires further quantitative investigation of smaller particles.

Conclusions The routine use of four-handed dentistry and rubber dam should continue where possible to maximise risk mitigation during AGPs. However, on the basis of our findings, the use of an EOS device can further mitigate the magnitude and concentration of splatter.
Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer
Authors: de Streel Grégoire , Bertrand Charlotte , Chalon Nicolas , Liénart Stéphanie , Bricard Orian , Lecomte Sara , Devreux Julien , Gaignage Mélanie , De Boeck Gitte , Mariën Lore , Van De Walle Inge , van der Woning Bas , Saunders Michael , de Haard Hans , Vermeersch Elien , Maes Wim , Deckmyn Hans , Coulie Pierre G. , van Baren Nicolas , Lucas Sophie
Published: September 2020

TGF-β1, β2 and β3 bind a common receptor to exert vastly diverse effects in cancer, supporting either tumor progression by favoring metastases and inhibiting anti-tumor immunity, or tumor suppression by inhibiting malignant cell proliferation. Global TGF-β inhibition thus bears the risk of undesired tumor-promoting effects. We show that selective blockade of TGF-β1 production by Tregs with antibodies against GARP:TGF-β1 complexes induces regressions of mouse tumors otherwise resistant to anti-PD-1 immunotherapy. Effects of combined GARP:TGF-β1/PD-1 blockade are immune-mediated, do not require FcγR-dependent functions and increase effector functions of anti-tumor CD8+T cells without augmenting immune cell infiltration or depleting Tregs within tumors. We find GARP-expressing Tregs and evidence that they produce TGF-β1 in one third of human melanoma metastases. Our results suggest that anti-GARP:TGF-β1 mAbs, by selectively blocking a single TGF-β isoform emanating from a restricted cellular source exerting tumor-promoting activity, may overcome resistance to PD-1/PD-L1 blockade in patients with cancer.
Designing and understanding light-harvesting devices with machine learning
Authors: Häse Florian , Roch Loïc M. , Friederich Pascal , Aspuru-Guzik Alán
Published: September 2020

Understanding the fundamental processes of light-harvesting is crucial to the development of clean energy materials and devices. Biological organisms have evolved complex metabolic mechanisms to efficiently convert sunlight into chemical energy. Unraveling the secrets of this conversion has inspired the design of clean energy technologies, including solar cells and photocatalytic water splitting. Describing the emergence of macroscopic properties from microscopic processes poses the challenge to bridge length and time scales of several orders of magnitude. Machine learning experiences increased popularity as a tool to bridge the gap between multi-level theoretical models and Edisonian trial-and-error approaches. Machine learning offers opportunities to gain detailed scientific insights into the underlying principles governing light-harvesting phenomena and can accelerate the fabrication of light-harvesting devices.
Demography and the emergence of universal patterns in urban systems
Authors: Bettencourt Luís M. A. , Zünd Daniel
Published: September 2020

Urban areas exist in a wide variety of population sizes, from small towns to huge megacities. No proposed form for the statistical distribution of city sizes has received more attention than Zipf’s law, a Pareto distribution with power law exponent equal to one. However, this distribution is typically violated by empirical evidence for small and large cities. Moreover, no theory presently exists to derive city size distributions from fundamental demographic choices while also explaining consistent variations. Here we develop a comprehensive framework based on demography to show how the structure of migration flows between cities, together with the differential magnitude of their vital rates, determine a variety of city size distributions. This approach provides a powerful mathematical methodology for deriving Zipf’s law as well as other size distributions under specific conditions, and to resolve puzzles associated with their deviations in terms of concepts of choice, symmetry, information, and selection.
Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor
Authors: Yang Jinsung , Petitjean Simon J. L. , Koehler Melanie , Zhang Qingrong , Dumitru Andra C. , Chen Wenzhang , Derclaye Sylvie , Vincent Stéphane P. , Soumillion Patrice , Alsteens David
Published: September 2020

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.
Defect and structural evolution under high-energy ion irradiation informs battery materials design for extreme environments
Authors: Rahman Muhammad Mominur , Chen Wei-Ying , Mu Linqin , Xu Zhengrui , Xiao Ziqi , Li Meimei , Bai Xian-Ming , Lin Feng
Published: September 2020

Understanding defect evolution and structural transformations constitutes a prominent research frontier for ultimately controlling the electrochemical properties of advanced battery materials. Herein, for the first time, we utilize in situ high-energy Kr ion irradiation with transmission electron microscopy to monitor how defects and microstructures evolve in Na- and Li-layered cathodes with 3d transition metals. Our experimental and theoretical analyses reveal that Li-layered cathodes are more resistant to radiation-induced structural transformations, such as amorphization than Na-layered cathodes. The underlying mechanism is the facile formation of Li-transition metal antisite defects in Li-layered cathodes. The quantitative mathematical analysis of the dynamic bright-field imaging shows that defect clusters preferentially align along the Na/Li ion diffusion channels (a-b planes), which is likely governed by the formation of dislocation loops. Our study provides critical insights into designing battery materials for extreme irradiation environments and understanding fundamental defect dynamics in layered oxides.
Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus
Authors: Kim Soyoun , Jung Dajung , Royer Sébastien
Published: September 2020

Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.
Amplification of enantiomeric excess by dynamic inversion of enantiomers in deracemization of Au38 clusters
Authors: Wang Yanan , Nieto-Ortega Belén , Bürgi Thomas
Published: September 2020

Symmetry breaking and amplification processes have likely played a fundamental role in the development of homochirality on earth. Such processes have not been much studied for inorganic matter at the nanoscale. Here, we show that the balance between left- and right-handed intrinsically chiral metal clusters can be broken by adsorbing a small amount of a chiral molecule in its ligand shell. We studied the amplification of enantiomeric excess of the Au38(2-PET)24 cluster (2-PET = 2-phenylethylthiolate). By exchanging a small fraction of the achiral 2-PET ligand by chiral R-1,1′-binaphthyl-2,2′-dithiol (R-BINAS), a mixture of species is obtained composed of anticlockwise (A) and clockwise (C) versions of Au38(2-PET)24 and Au38(2-PET)22(R-BINAS)1. At 70 °C, the system evolves towards the anticlockwise clusters at the expense of the clockwise antipode. It is shown that the interplay between the diastereospecific ligand exchange, which introduces selectivity but does not change the A/C ratio, and the fast racemization of the Au38(2-PET)24 is at the origin of this observation.
Polariton-driven phonon laser
Authors: Chafatinos D. L. , Kuznetsov A. S. , Anguiano S. , Bruchhausen A. E. , Reynoso A. A. , Biermann K. , Santos P. V. , Fainstein A.
Published: September 2020

Efficient generation of phonons is an important ingredient for a prospective electrically-driven phonon laser. Hybrid quantum systems combining cavity quantum electrodynamics and optomechanics constitute a novel platform with potential for operation at the extremely high frequency range (30–300 GHz). We report on laser-like phonon emission in a hybrid system that optomechanically couples polariton Bose-Einstein condensates (BECs) with phonons in a semiconductor microcavity. The studied system comprises GaAs/AlAs quantum wells coupled to cavity-confined optical and vibrational modes. The non-resonant continuous wave laser excitation of a polariton BEC in an individual trap of a trap array, induces coherent mechanical self-oscillation, leading to the formation of spectral sidebands displaced by harmonics of the fundamental 20 GHz mode vibration frequency. This phonon “lasing” enhances the phonon occupation five orders of magnitude above the thermal value when tunable neighbor traps are red-shifted with respect to the pumped trap BEC emission at even harmonics of the vibration mode. These experiments, supported by a theoretical model, constitute the first demonstration of coherent cavity optomechanical phenomena with exciton polaritons, paving the way for new hybrid designs for quantum technologies, phonon lasers, and phonon-photon bidirectional translators.
Diversity analysis of 80,000 wheat accessions reveals consequences and opportunities of selection footprints
Authors: Sansaloni Carolina , Franco Jorge , Santos Bruno , Percival-Alwyn Lawrence , Singh Sukhwinder , Petroli Cesar , Campos Jaime , Dreher Kate , Payne Thomas , Marshall David , Kilian Benjamin , Milne Iain , Raubach Sebastian , Shaw Paul , Stephen Gordon , Carling Jason , Pierre Carolina Saint , Burgueño Juan , Crosa José , Li HuiHui , Guzman Carlos , Kehel Zakaria , Amri Ahmed , Kilian Andrzej , Wenzl Peter , Uauy Cristobal , Banziger Marianne , Caccamo Mario , Pixley Kevin
Published: September 2020

Undomesticated wild species, crop wild relatives, and landraces represent sources of variation for wheat improvement to address challenges from climate change and the growing human population. Here, we study 56,342 domesticated hexaploid, 18,946 domesticated tetraploid and 3,903 crop wild relatives in a massive-scale genotyping and diversity analysis. Using DArTseqTMtechnology, we identify more than 300,000 high-quality SNPs and SilicoDArT markers and align them to three reference maps: the IWGSC RefSeq v1.0 genome assembly, the durum wheat genome assembly (cv. Svevo), and the DArT genetic map. On average, 72% of the markers are uniquely placed on these maps and 50% are linked to genes. The analysis reveals landraces with unexplored diversity and genetic footprints defined by regions under selection. This provides fertile ground to develop wheat varieties of the future by exploring specific gene or chromosome regions and identifying germplasm conserving allelic diversity missing in current breeding programs.