bluuebunny/crossref_metadata_2025 huggingface dataset:
Stretchable distributed fiber-optic sensors
Authors: Bai Hedan , Li Shuo , Barreiros Jose , Tu Yaqi , Pollock Clifford R. , Shepherd Robert F.
Published: November 2020

Colorful changes

Distributed fiber-optic sensors have been used for monitoring mechanical deformations in stiff infrastructures such as bridges, roads, and buildings, but they either are limited to measuring one variable or require complex optics to measure multiple properties. Bai
et al.
now demonstrate dual-core elastomeric optical fibers, one of which contains patterned dye regions. The waveguides are fabricated by molding out of commercially available elastomers and integrate a clear core and an adjacent core doped with up to three macroscale dye regions. Changes in optical paths in the two cores detect deformation and map it onto a color space. By monitoring changes in the color and intensity in both elastomer-based fibers, the researchers could distinguish bending, stretching, and localized pressing with a spatial resolution down to ∼1 centimeter.

Science
, this issue p.
848
Terrestrial radiative cooling: Using the cold universe as a renewable and sustainable energy source
Authors: Yin Xiaobo , Yang Ronggui , Tan Gang , Fan Shanhui
Published: November 2020

Photonic materials designed at wavelength scales have enabled a range of emerging energy technologies, from solid-state lighting to efficient photovoltaics that have transformed global energy landscapes. Daytime passive radiative cooling materials shed heat from the ground to the cold universe by taking advantage of the terrestrial thermal radiation that is as large as the renewable solar energy. Newly developed photonic materials permit subambient cooling under direct sunshine, and their applications are expanding rapidly enabled by scalable manufacturing. We review here the recent advancement of daytime subambient radiative cooling materials, which allow energy-efficient cooling and are paving the way toward technologies that harvest the coldness from the universe as a new renewable energy source.
A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress
Authors: Lamper Adam M. , Fleming Rebecca H. , Ladd Kayla M. , Lee Amy S. Y.
Published: November 2020

Cellular adaptation during metabolic stress

Cells respond to environmental stress by down-regulating general protein synthesis and inducing selective expression of proteins required for survival. However, the mechanisms controlling this selective messenger RNA (mRNA) translation response remain poorly understood. Lamper
et al.
report that the noncanonical 5′ cap-binding protein subunit eIF3d is activated upon metabolic stress in mammalian cells to reprogram cellular mRNA translation. eIF3d is activated by a switch in phosphorylation status at sites near the cap-binding pocket and enables cells to express the proteins required for the regulation of metabolism and survival during stresses, including glucose starvation. This work reveals how eIF3d-dependent, noncanonical cap-dependent translation controls the cellular adaptation to stress.

Science
, this issue p.
853
Cell wall remodeling and vesicle trafficking mediate the root clock in
Arabidopsis
Authors: Wachsman Guy , Zhang Jingyuan , Moreno-Risueno Miguel A. , Anderson Charles T. , Benfey Philip N.
Published: November 2020

Signaling for a weakness in cell walls

Lateral roots form at regular intervals in the small mustard plant
Arabidopsis thaliana
. Wachsman
et al.
have now identified both pectin and subcellular vesicle trafficking as part of the oscillating signaling system that initiates lateral roots. Esterification of pectin regulates its function at the nascent lateral root site, altering the stiffness of cell walls and the strength of cell-cell adhesion. Because lateral root primordia must push through overlying cell layers, reduced cell adhesion at these sites might aid in the formation of lateral roots.

Science
, this issue p.
819
A thalamocortical top-down circuit for associative memory
Authors: Pardi M. Belén , Vogenstahl Johanna , Dalmay Tamas , Spanò Teresa , Pu De-Lin , Naumann Laura B. , Kretschmer Friedrich , Sprekeler Henning , Letzkus Johannes J.
Published: November 2020

Higher-order thalamus input to the cortex

Sensory information can only be used meaningfully in the brain when integrated with and compared with internally generated top-down signals. However, we know little about the brainwide afferents that convey such top-down signals, their information content, and learning-related plasticity. Pardi
et al.
identified the higher-order thalamus as a major source of top-down input to mouse auditory cortex and investigated a circuit in cortical layer 1 that facilitates plastic changes and flexible responses. These results demonstrate how top-down feedback information can reach cortical areas through a noncortical structure that has received little attention despite its widespread connections with the cortex.

Science
, this issue p.
844
A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming
Authors: Han Jaeil , LaVigne Collette A. , Jones Benjamin T. , Zhang He , Gillett Frank , Mendell Joshua T.
Published: November 2020

Turning the tables on microRNA decay

MicroRNAs help to regulate many genes in animal cells. Each microRNA associates with an Argonaute (AGO) protein, forming a complex in which the microRNA pairs with a messenger RNA (mRNA) target and AGO recruits factors that accelerate mRNA decay. However, for some unusual targets, the reverse occurs: Pairing to the target recruits factors that accelerate microRNA decay rather than degradation of the mRNA. Working independently, Shi
et al.
and Han
et al.
elucidate the mechanism of this phenomenon. They found that pairing to the unusual targets recruits a ubiquitin ligase that causes degradation of AGO, thereby exposing the microRNA to cellular nucleases. Mutating the ubiquitin ligase in diverse animals and cell types deregulates numerous microRNAs, implying that this phenomenon is widely deployed to sculpt microRNA levels.

Science
, this issue p.
eabc9359
, p.
eabc9546
Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water
Authors: Foden Callum S. , Islam Saidul , Fernández-García Christian , Maugeri Leonardo , Sheppard Tom D. , Powner Matthew W.
Published: November 2020

Cysteine as peptide precursor and catalyst

Among amino acids, cysteine is highly reactive as a nucleophile, metal ligand, and participant in redox and radical reactions. These properties make cysteine attractive as a component of prebiotic chemistry, but traditional Strecker synthesis of α-aminonitriles, which can serve as peptide precursors, cannot produce free cysteine. Foden
et al.
found that a simple acylation of the free amine prevented degradation of cysteine nitrile and enabled synthesis of this cysteine precursor from acetyl dehydroalanine nitrile and a sulfide donor (see the Perspective by Muchowska and Moran). When combined with other proteinogenic α-aminonitriles, acetylcysteine or derivative thiols catalyzed efficient peptide ligation in water. These results highlight how prebiotic synthesis of precursors can also generate function by creating a catalyst for polymerization.

Science
, this issue p.
865
; see also p.
767
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
Authors: Hou Yixuan J. , Chiba Shiho , Halfmann Peter , Ehre Camille , Kuroda Makoto , Dinnon Kenneth H. , Leist Sarah R. , Schäfer Alexandra , Nakajima Noriko , Takahashi Kenta , Lee Rhianna E. , Mascenik Teresa M. , Graham Rachel , Edwards Caitlin E. , Tse Longping V. , Okuda Kenichi , Markmann Alena J. , Bartelt Luther , de Silva Aravinda , Margolis David M. , Boucher Richard C. , Randell Scott H. , Suzuki Tadaki , Gralinski Lisa E. , Kawaoka Yoshihiro , Baric Ralph S.
Published: November 2020

Changing with the times

Pandemic spread of a virus in naïe populations can select for mutations that alter pathogenesis, virulence, and/or transmissibility. The ancestral form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged from China has now been largely replaced by strains containing the mutation D614G (Asp
614
-to-Gly) in the viral spike protein. Hou
et al.
compared the characteristics of the new variant against the ancestral form in a series of experiments in human cells and animal models. The variant is better at infecting upper-airway epithelial cells and replicates in greater numbers than the ancestral virus. Evidence indicates modest, if any, significant changes to virulence in animal models. Therefore, the virus appears to have evolved for greater transmissibility in humans rather than for greater pathogenicity. The mutation renders the new virus variant more susceptible to neutralizing antisera without altering the efficacy of vaccine candidates currently under development.

Science
, this issue p.
1464
Supplemental Material: From Ordovician nascent to early Permian mature arc in the southern Altaids: Insights from the Kalatage inlier in the Eastern Tianshan, NW China
Authors: Mao Q.G. , al. et , Xiao W.J.
Published: November 2020

Zircon SIMS, LA-ICP-MS, and SHRIMP U-Pb geochronological dating, major, and trace element data (listed in Supplemental Tables S1 to S5, respectively).
Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns
Authors: Assi Emma , D'Addio Francesca , Mandò Chiara , Maestroni Anna , Loretelli Cristian , Ben Nasr Moufida , Usuelli Vera , Abdelsalam Ahmed , Seelam Andy Joe , Pastore Ida , Magagnotti Cinzia , Abdi Reza , El Essawy Basset , Folli Franco , Corradi Domenico , Zuccotti Gianvincenzo , Cetin Irene , Fiorina Paolo
Published: November 2020

Introduction

Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood.

Research design and methods

A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs).

Results

Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities.

Conclusions

Our findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking.
Temporal trends in coverage, quality and equity of maternal and child health services in Rwanda, 2000–2015
Authors: Hategeka Celestin , Arsenault Catherine , Kruk Margaret E
Published: November 2020

Introduction

Achieving the maternal and child health (MCH)-related Sustainable Development Goals (SDG) will require equitable and effective (quality-adjusted) coverage of recommended health interventions in low- and middle-income countries. We assessed effective coverage and equity of MCH services in Rwanda in the Millennium Development Goal (MDG) era to help guide policy decisions to improve equitable health gains in the SDG era and beyond.

Methods

Using four rounds of Rwanda demographic and health surveys conducted from 2000 to 2015, we identified coverage and quality indicators for five MCH services: antenatal care (ANC), delivery care, and care for child diarrhoea, suspected pneumonia and fever. We calculated crude coverage and quality in each survey and used these to estimate effective coverage. The effective coverage should be regarded as an upper bound because there were few available quality measures. We also described equity in effective coverage of these five MCH services over time across the wealth index, area of residence and maternal education using equiplots.

Results

A total of 48 910 women aged 15–49 years and 33 429 children under 5 years were included across the four survey rounds. In 2015, average effective coverage was 33.2% (range 19.9%–44.2%) across all five MCH services, 30.1% (range 19.9%–40.2%) for maternal health services (average of ANC and delivery) and 35.3% (range 27.3%–44.2%) for sick child care (diarrhoea, pneumonia and fever). This is in contrast to crude coverage which averaged 56.5% (range 43.6%–90.7%) across all five MCH services, 67.3% (range 43.9%–90.7%) for maternal health services and 49.2% (range 43.6%–53.9%) for sick child care. Between 2010 and 2015 effective coverage increased by 154.2% (range 127.3%–170.0%) for maternal health services and by 27.4% (range 4.2%–79.6%) for sick child care. These increases were associated with widening socioeconomic inequalities in effective coverage for maternal health services, and narrowing inequalities in effective coverage for sick child care.

Conclusion

While effective coverage of common MCH services generally improved in the MDG era, it still lagged substantially behind crude coverage for the same services due to low-quality care. Overall, effective coverage of MCH services remained suboptimal and inequitable. Policies should focus on improving effective coverage of these services and reducing inequities.
Does retraction after misconduct have an impact on citations? A pre–post study
Authors: Candal-Pedreira Cristina , Ruano-Ravina Alberto , Fernández Esteve , Ramos Jorge , Campos-Varela Isabel , Pérez-Ríos Mónica
Published: November 2020

Background

Retracted articles continue to be cited after retraction, and this could have consequences for the scientific community and general population alike. This study was conducted to analyse the association of retraction on citations received by retracted papers due to misconduct using two-time frames: during a postretraction period equivalent to the time the article had been in print before retraction; and during the total postretraction period.

Methods

Quasiexperimental, pre–post evaluation study. A total of 304 retracted original articles and literature reviews indexed in MEDLINE fulfilled the inclusion criteria. Articles were required to have been published in a journal indexed in MEDLINE from January 2013 through December 2015 and been retracted between January 2014 and December 2016. The main outcome was the number of citations received before and after retraction. Results were broken down by journal quartile according to impact factor and the most cited papers during the preretraction period were specifically analysed.

Results

There was an increase in postretraction citations when compared with citations received preretraction. There were some exceptions however: first, citations received by articles published in first-quartile journals decreased immediately after retraction (p<0.05), only to increase again after some time had elapsed; and second, postretraction citations decreased significantly in the case of articles that had received many citations before their retraction (p<0.05).

Conclusions

The results indicate that retraction of articles has no association on citations in the long term, since the retracted articles continue to be cited, thus circumventing their retraction.
Producing a new website for a paediatric liaison mental health team with our service users
Authors: Adams Alexander , Davies Virginia , Stubbs Bethany
Published: November 2020

Introduction

Online resources are an important source of information about mental health issues and services for children and young people. Our service’s website had an out-of-date appearance and was aimed at professionals. More importantly, comments in our routinely collected patient experience data indicated that service users did not know what to expect when coming to our service.

Methods

We followed the model for improvement by testing out changes in plan, do, study and act cycles that included a review of recently updated child and adolescent mental health services’ and youth charities’ websites, designing a new web page for our service and then testing out the website in focus groups. We used routinely collected patient experience data to assess impact on wider patient satisfaction.

Results

Focus groups involving patients, parents and professionals judged the new website to be clearer, more attractive and easier to understand. Routine patient experience data did not reveal any website-specific feedback.

Conclusion

This study demonstrates that it is easy and possible to create an attractive and accessible website for a mental health service using quality improvement methodology. In order to capture and integrate ongoing feedback about a service’s website from service users, routinely collected patient experience measures would need to ask specific questions related to this area. In this study, preproject and postproject patient experience data did not generate any specific comments.
Clinical workflow: a useful tool to improve staff retention, practice efficiency and staff wellbeing
Authors: Page Gillian
Published: November 2020

Clinical workflow should involve all levels of a veterinary business, and covers many different aspects of the day‐to‐day runnings of a practice; staff and client communications, tasks involved in a particular procedure, the team structure and the timeline of a patient's journey. This article highlights why a workflow restructure can be hugely beneficial for staff retention, wellbeing and business longevity.
Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity
Authors: Efimova Iuliia , Catanzaro Elena , Van der Meeren Louis , Turubanova Victoria D , Hammad Hamida , Mishchenko Tatiana A , Vedunova Maria V , Fimognari Carmela , Bachert Claus , Coppieters Frauke , Lefever Steve , Skirtach Andre G , Krysko Olga , Krysko Dmitri V
Published: November 2020

Background

Immunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown.

Methods

Ferroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c+CD86+, CD11c+CD40+, CD11c+MHCII+, IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2−/−) mice was used to analyze ferroptosis immunogenicity.

Results

Ferroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors’ analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells.

Conclusions

These results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy.
Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
Authors: Sun Roger , Sundahl Nora , Hecht Markus , Putz Florian , Lancia Andrea , Rouyar Angela , Milic Marina , Carré Alexandre , Battistella Enzo , Alvarez Andres Emilie , Niyoteka Stéphane , Romano Edouard , Louvel Guillaume , Durand-Labrunie Jérôme , Bockel Sophie , Bahleda Rastilav , Robert Charlotte , Boutros Celine , Vakalopoulou Maria , Paragios Nikos , Frey Benjamin , Soria Jean-Charles , Massard Christophe , Ferté Charles , Fietkau Rainer , Ost Piet , Gaipl Udo , Deutsch Eric
Published: November 2020

Background

Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions.

Methods

Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient’s response.

Results

A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables.

Conclusions

These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy
Authors: Simon Sylvain , Voillet Valentin , Vignard Virginie , Wu Zhong , Dabrowski Camille , Jouand Nicolas , Beauvais Tiffany , Khammari Amir , Braudeau Cécile , Josien Régis , Adotevi Olivier , Laheurte Caroline , Aubin François , Nardin Charles , Rulli Samuel , Gottardo Raphael , Ramchurren Nirasha , Cheever Martin , Fling Steven P , Church Candice D , Nghiem Paul , Dreno Brigitte , Riddell Stanley R , Labarriere Nathalie
Published: November 2020

Background

Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.

Methods

We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.

Results

We documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.

Conclusions

Our results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.
Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia
Authors: Ward David D , Wallace Lindsay M K , Rockwood Kenneth
Published: November 2020

Objective

To determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.

Methods

A frailty index was calculated using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer’s Coordinating Center. Cognitive status was determined by clinical evaluation. Using multistate transition models, we assessed the extent to which an increasing degree of frailty affected the probabilities of transitioning between not cognitively impaired (NCI), MCI, and dementia.

Results

Participants (n=14 490) had a mean age of 72.2 years (SD=8.9 years; range=50–103 years). Among those NCI at baseline (n=9773), each 0.1 increment increase in the frailty index was associated with a higher risk of developing MCI and a higher risk of progressing to dementia. Among those with MCI at baseline (n=4717), higher frailty was associated with a higher risk of progressing to dementia, a lower probability of being reclassified as NCI, and a higher likelihood of returning to MCI in those that were reclassified as NCI. These risk effects were present and similar in both carriers and non-carriers of the APOE ε4 allele.

Conclusion

Among older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value.
Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research
Authors: Kerschbaumer Andreas , Smolen Josef S , Nash Peter , Doerner Thomas , Dougados Maxime , Fleischmann Roy , Geissler Klaus , McInnes Iain B , Takeuchi Tsutomu , Trauner Michael , Winthrop Kevin , de Wit Maarten , Boehncke Wolf-Henning , Falzon Louise , van der Heijde Desirée
Published: November 2020

Objectives

Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs).

Methods

A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation.

Results

3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn’s disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed.

Conclusion

JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.
Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole: results of a multicentre, randomised controlled trial
Authors: Dean Gillian , Soni Suneeta , Pitt Rachel , Ross Jonathan , Sabin Caroline , Whetham Jennifer
Published: November 2020

Objective

A multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days of azithromycin and metronidazole (intervention arm (IA)) in women with mild-to-moderate pelvic inflammatory disease (PID).

Methods

Women with a clinical diagnosis of PID presenting at sexual health services were randomised to the SoC or IA arms. Treating clinicians and participants were not blinded to treatment allocation but the clinician performing the assessment of primary outcome was blinded. The primary outcome was clinical cure defined as ≥70% reduction in the modified McCormack pain score at day 14–21 after starting treatment. Secondary outcomes included adherence, tolerability and microbiological cure.

Results

Of the randomised population 72/153 (47.1%) reached the primary end point in the SoC arm, compared with 68/160 (42.5%) in the IA (difference in cure 4.6% (95% CI −15.6% to 6.5%). Following exclusion of 86 women who were lost to follow-up, attended outside the day 14–21 follow-up period, or withdrew consent, 72/107 (67.3%) had clinical cure in the SoC arm compared with 68/120 (56.7%) in the IA, giving a difference in cure rate of 10.6% (95% CI −23.2% to 1.9%). We were unable to demonstrate non-inferiority of the IA compared with SoC arm. Women in the IA took more treatment doses compared with the SoC group (113/124 (91%) vs 75/117 (64%), p=0.0001), but were more likely to experience diarrhoea (61% vs 24%, p<0.0001). Of 288 samples available for analysis,
Mycoplasma genitalium
was identified in 10% (28/288), 58% (11/19) of which had baseline antimicrobial resistance-associated mutations.

Conclusion

A short-course azithromycin-based regimen is likely to be less effective than the standard treatment with ofloxacin plus metronidazole. The high rate of baseline antimicrobial resistance supports resistance testing in those with
M. genitalium
infection to guide appropriate therapy.

Trial registration number

2010-023254-36.
Resonance free domain for a system of Schrödinger operators with energy-level crossings
Authors: Higuchi Kenta
Published: November 2020

We consider a [Formula: see text] system of 1D semiclassical differential operators with two Schrödinger operators in the diagonal part and small interactions of order [Formula: see text] in the off-diagonal part, where [Formula: see text] is a semiclassical parameter and [Formula: see text] is a constant larger than [Formula: see text]. We study the absence of resonance near a non-trapping energy for both Schrödinger operators in the presence of crossings of their potentials. The width of resonances is estimated from below by [Formula: see text] and the coefficient [Formula: see text] is given in terms of the directed cycles of the generalized bicharacteristics induced by two Hamiltonians.
A disease transmission model based on individual cognition
Authors: Nian Fuzhong , Shi Yayong , Dang Zhongkai
Published: November 2020

Recently, the study about the disease transmission has received widespread attention. In the dynamics process of infectious disease, individual’s cognition about disease-related knowledge is an important factor that controls disease transmission. The disease-related information includes the cause, symptoms, transmission route and so on. Disease-related knowledge would influence the individual’s attitude toward disease, and influence the transmission rate and scale of the infectious disease. In order to study the impact of individual cognition on the transmission of disease, the disease transmission model based on individual cognition is proposed in this paper. Based on this model, we numerically simulate the transmission of disease in the small-world network and the BA scale-free network, respectively, and analyze the transmission dynamics behavior of the infectious disease. The simulation experiment verifies the validity of the theoretical result, which shows that this model is closer to the reality than traditional models.
Wong–Zakai approximations and attractors for stochastic degenerate parabolic equations on unbounded domains
Authors: Miao Fahe , Liu Hui , Xin Jie
Published: November 2020

The Wong–Zakai approximations given by a stationary process and attractors for stochastic degenerate parabolic equations are considered in this paper. We first establish the existence and uniqueness of tempered pullback attractors for the Wong–Zakai approximations of stochastic degenerate parabolic equations. We then prove that the attractors of Wong–Zakai approximations converge to the attractor of stochastic degenerate parabolic equations driven by multiplicative white noise.
THE ROLE OF FAMILY GOVERNANCE BEYOND FINANCIAL RATIOS: AN INTEGRATED PERSPECTIVE ON FAMILY FIRMS’ SURVIVAL
Authors: GALLUCCI CARMEN , SANTULLI ROSALIA , MODINA MICHELE , DE ROSA MICHELA
Published: November 2020

In the years following the economic and financial crisis, Italy, where most firms are family-owned, has seen the demise of more companies than any other country. To avoid a similar disaster in the future, it is important to understand which determinants influence firms’ survival. Stemming from financial and family business literature, this paper investigates the role of financial ratios and family corporate governance in predicting family firms’ survival probability. To obtain empirical evidence, it performs a mediating regression analysis using a sample of 273 Italian family firms. The main findings show that family ownership concentration and the presence of a family CEO increase firms’ survival probability, while a high number of family members involved in the firm and the co-presence of more generations hinder it.
Inhibition of ATGL in adipose tissue ameliorates isoproterenol-induced cardiac remodeling by reducing adipose tissue inflammation
Authors: Takahara Shingo , Ferdaoussi Mourad , Srnic Nikola , Maayah Zaid H. , Soni Shubham , Migglautsch Anna K. , Breinbauer Rolf , Kershaw Erin E. , Dyck Jason R. B.
Published: November 2020

The reduction of lipolysis by adipocyte ATGL inhibition ameliorates cardiac remodeling induced by chronic β-adrenergic stimulation likely via reducing galectin-3 secretion from adipose tissue. Our findings highlight that suppressing lipolysis in adipocytes may be a potential therapeutic target for patients with heart failure whose sympathetic nervous system is activated. Furthermore, galectin-3 might be involved in the mechanisms by which excessive lipolysis in adipose tissues influences remote cardiac pathologies and thus warrants further investigation.
Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis
Authors: Lin Hexin , Zhao Xin , Xia Lu , Lian Jiabian , You Jun
Published: November 2020

Background. Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods. PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results. Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients’ increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis:

HR
=
1.81

, 95% CI 1.46-2.25; multivariate analysis:

HR
=
1.95

, 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma (

HR
=
3.31

, 95% CI 2.03-5.39), lung cancer (

HR
=
1.66

, 95% CI 1.21-2.29), genitourinary cancer (

HR
=
2.03

, 95% CI 1.15-3.58), and digestive cancer (

HR
=
1.48

, 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis (

OR
=
2.96

, 95% CI 1.42-6.20) and lager tumor size (

OR
=
1.60

, 95% CI 1.12-2.28). Conclusion. The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.
Airborne Integrated Navigation System Based on SINS/GPS/TAN/EOAN
Authors: Tang Junjun , Li Peijuan
Published: November 2020

Considering the drawbacks that GPS signal is susceptible to obstacles and TAN becomes useless in some area when without any terrain data or with a featureless terrain field, to realize long-distance and high-precision navigation, a navigation system based on SINS/GPS/TAN/EOAN is presented. When GPS signal is available, GPS is used to correct errors of SINS; when GPS is unavailable, a terrain selection method based on the entropy weighted gray relational decision-making method is use to distinguish terrain into matchable areas and unmatchable areas; then, for the matchable areas, TAN is used to correct errors of SINS, for the unmatchable areas, EOAN is used to correct errors of SINS. The principles of SINS, GPS, TAN, and EOAN are analyzed, the mathematic models of SINS/GPS, SINS/TAN, and SINS/EOAN are constructed, and finally the federated Kalman filter is used to fuse navigation information. Simulation results show that the trajectory of SINS/GPS/TAN/EOAN is close to the ideal one in both matchable area or unmatchable area and whose navigation errors are obviously reduced, which is important for the realization of long-time and high-precision positioning.
Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases
Authors: Al-Madol Mohammed A. , Shaqura Mohammed , John Thilo , Likar Rudolf , Ebied Reham Said , Salih Magdi M. , Treskatsch Sascha , Schäfer Michael , Mousa Shaaban A.
Published: November 2020

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients.
Catastrophizing Has a Better Prediction for TMD Than Other Psychometric and Experimental Pain Variables
Authors: Willassen Lisa , Johansson Anders Arne , Kvinnsland Siv , Staniszewski Kordian , Berge Trond , Rosén Annika
Published: November 2020

Temporomandibular disorders (TMDs) are characterized by moderate to severe pain in the masticatory muscles and/or the temporomandibular joint (TMJ). The present study is a part of a multidisciplinary project, initiated by the Norwegian Ministry of Health. The main purpose of this study is to compare a cohort of TMD patients to healthy individuals regarding experimental pain, the degree of disability caused by living with pain and psychometric variables, and to investigate which of these variables is the best predictor for TMD patients. We hypothesised that TMD patients have more disability when living with pain and lower pain thresholds than healthy controls, and those psychometric variables are stronger predictors than pain thresholds provoked by experimental pain. Sixty TMD patients were matched by sex and age to sixty healthy individuals without TMD symptoms or other musculoskeletal symptoms in the head and neck region. All subjects completed a questionnaire that included psychometric characteristics, that is, a one- and two-item version of the Pain Catastrophizing Scale, the Hospital Anxiety and Depression Scale (HADS), and the Roland Morris Scale (RMS), which measures disability when living with pain. They also underwent a clinical examination including the measurement of pain thresholds with electrical and pressure stimuli. The TMD patients had lower pain thresholds for experimental electrical and pressure stimuli compared with the controls (

P

 < 0.05 and <0.001, respectively). They also scored higher than healthy individuals with disability living with pain (

P
<
0.001

), anxiety (

P
<
0.001

), depression (

P
<
0.001

), and catastrophizing (

P
<
0.001

). The results for anxiety, depression, and catastrophizing have been published earlier, and the reused data in this study are compared with RMS and pain thresholds. The conditional logistic regression model identified catastrophizing (OR = 2.42, CI 1.22–4.79) as a significant predictor of TMD patients. The results support this hypothesis and indicate that TMD patients have lower pain thresholds and more disability when living with pain compared to healthy individuals, where the strongest prediction for TMD was catastrophizing. Awareness of psychometric disabilities in TMD patients is of importance when considering the choice of treatment.
The Impact of Preconception TSH on the Reproductive Outcomes of Infertile Women Undergoing the First Fresh D3 Embryo Transfer Cycle
Authors: Zhang Yuchao , Wu Wenbin , Liu Yanli , Guan Yichun , Wang Xingling , Jia Liting
Published: November 2020

Purpose. To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Methods. This was a retrospective study. Euthyroid patients undergoing the first fresh D3 embryo transfer from January 2018 to May 2019 were initially included. The patients were divided into a low-TSH (0.27–2.5 mIU/L) group and a high-normal TSH (2.5–4.2 Miu) group. The reproductive outcomes were compared between the groups. Results. A total of 1786 women were ultimately included, in which 1008 of whom had serum TSH levels between 0.27 and 2.5 mIU/L and 778 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.92, 1.30, and 0.88 and

P

 = 0.416, 0.163, and 0.219). No significant differences were observed in terms of gestational age, single live birth rates, and birth weight, or birth length. Conclusion. High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population.
An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats
Authors: Shen Xueyan , Luo Lu , Wang Fei , Yu Kewei , Xie Hongyu , Tian Shan , Liu Gang , Bao Chunrong , Fan Yunhui , Xing Ying , Wang Nianhong , Li Siyue , Liu Li , Zhang Qun , Wu Yi
Published: November 2020

An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.