bluuebunny/crossref_metadata_2025 huggingface dataset:
Human organ rejuvenation by VEGF-A: Lessons from the skin
Authors: Keren Aviad , Bertolini Marta , Keren Yaniv , Ullmann Yehuda , Paus Ralf , Gilhar Amos
Published: June 2022

Transplanting aged human skin onto young SCID/beige mice morphologically rejuvenates the xenotransplants. This is accompanied by angiogenesis, epidermal repigmentation, and substantial improvements in key aging-associated biomarkers, including ß-galactosidase, p16
ink4a
, SIRT1, PGC1α, collagen 17A, and MMP1. Angiogenesis- and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIF1A, are most up-regulated in rejuvenated human skin. This rejuvenation cascade, which can be prevented by VEGF-A–neutralizing antibodies, appears to be initiated by murine VEGF-A, which then up-regulates VEGF-A expression/secretion within aged human skin. While intradermally injected VEGF-loaded nanoparticles suffice to induce a molecular rejuvenation signature in aged human skin on old mice, VEGF-A treatment improves key aging parameters also in isolated, organ-cultured aged human skin, i.e., in the absence of functional skin vasculature, neural, or murine host inputs. This identifies VEGF-A as the first pharmacologically pliable master pathway for human organ rejuvenation in vivo and demonstrates the potential of our humanized mouse model for clinically relevant aging research.
Reducing opioid use disorder and overdose deaths in the United States: A dynamic modeling analysis
Authors: Stringfellow Erin J. , Lim Tse Yang , Humphreys Keith , DiGennaro Catherine , Stafford Celia , Beaulieu Elizabeth , Homer Jack , Wakeland Wayne , Bearnot Benjamin , McHugh R. Kathryn , Kelly John , Glos Lukas , Eggers Sara L. , Kazemi Reza , Jalali Mohammad S.
Published: June 2022

Opioid overdose deaths remain a major public health crisis. We used a system dynamics simulation model of the U.S. opioid-using population age 12 and older to explore the impacts of 11 strategies on the prevalence of opioid use disorder (OUD) and fatal opioid overdoses from 2022 to 2032. These strategies spanned opioid misuse and OUD prevention, buprenorphine capacity, recovery support, and overdose harm reduction. By 2032, three strategies saved the most lives: (i) reducing the risk of opioid overdose involving fentanyl use, which may be achieved through fentanyl-focused harm reduction services; (ii) increasing naloxone distribution to people who use opioids; and (iii) recovery support for people in remission, which reduced deaths by reducing OUD. Increasing buprenorphine providers’ capacity to treat more people decreased fatal overdose, but only in the short term. Our analysis provides insight into the kinds of multifaceted approaches needed to save lives.
Locally controllable magnetic soft actuators with reprogrammable contraction-derived motions
Authors: Wu Yahe , Zhang Shuai , Yang Yang , Li Zhen , Wei Yen , Ji Yan
Published: June 2022

Reprogrammable magneto-responsive soft actuators capable of working in enclosed and confined spaces and adapting functions under changing situations are highly demanded for new-generation smart devices. Despite the promising prospect, the realization of versatile morphing modes (more than bending) and local magnetic control remains challenging but is crucial for further on-demand applications. Here, we address the challenges by maximizing the unexplored potential of magnetothermal responsiveness and covalent adaptable networks (CANs) in liquid crystalline elastomers (LCEs). Various magneto-actuated contraction-derived motions that were hard to achieve previously (e.g., bidirectional shrinkage and dynamic 3D patterns) can be attained, reprogrammed, and assembled seamlessly to endow functional diversity and complexity. By integration of LCEs with different magneto-responsive threshold values, local and sequential magnetic control is readily realized. Many magnetic actuation portfolios are performed by rationally imputing “logic switch” sequences. Meanwhile, our systems exhibit additional favorable performances including stepwise magnetic controllability, multiresponsiveness, self-healing, and remolding ability.
Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme
Authors: Le Huray Kyle I. P. , Bunney Tom D. , Pinotsis Nikos , Kalli Antreas C. , Katan Matilda
Published: June 2022

PLCγ enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCγ require understanding of an active, membrane-bound form, which can hydrolyze inositol-lipid substrates. Here, we demonstrate that PLCγ1 cannot bind membranes unless the autoinhibition is disrupted. Through extensive molecular dynamics simulations and experimental evidence, we characterize membrane binding by the catalytic core domains and reveal previously unknown sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces, and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLCγ1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCγ1 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention.
Gasdermin D–mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma
Authors: Yamagishi Ryota , Kamachi Fumitaka , Nakamura Masaru , Yamazaki Shota , Kamiya Tomonori , Takasugi Masaki , Cheng Yi , Nonaka Yoshiki , Yukawa-Muto Yoshimi , Thuy Le Thi Thanh , Harada Yohsuke , Arai Tatsuya , Loo Tze Mun , Yoshimoto Shin , Ando Tatsuya , Nakajima Masahiro , Taguchi Hayao , Ishikawa Takamasa , Akiba Hisaya , Miyake Sachiko , Kubo Masato , Iwakura Yoichiro , Fukuda Shinji , Chen Wei-Yu , Kawada Norifumi , Rudensky Alexander , Nakae Susumu , Hara Eiji , Ohtani Naoko
Published: June 2022

Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, using a mouse model of obesity-induced hepatocellular carcinoma (HCC), we identified the release mechanism of SASP factors, which include interleukin-1β (IL-1β)– and IL-1β–dependent IL-33, from senescent hepatic stellate cells (HSCs) via gasdermin D (GSDMD) amino-terminal–mediated pore. We found that IL-33 was highly induced in senescent HSCs in an IL-1β–dependent manner in the tumor microenvironment. The release of both IL-33 and IL-1β was triggered by lipoteichoic acid (LTA), a cell wall component of gut microbiota that was transferred and accumulated in the liver tissue of high-fat diet–fed mice, and the release of these factors was mediated through cell membrane pores formed by the GSDMD amino terminus, which was cleaved by LTA-induced caspase-11. We demonstrated that IL-33 release from HSCs promoted HCC development via the activation of ST2-positive T
reg
cells in the liver tumor microenvironment. The accumulation of GSDMD amino terminus was also detected in HSCs from human NASH-associated HCC patients, suggesting that similar mechanism could be involved in a certain type of human HCC. These results uncover a release mechanism for SASP factors from sensitized senescent HSCs in the tumor microenvironment, thereby facilitating obesity-associated HCC progression. Furthermore, our findings highlight the therapeutic potential of inhibitors of GSDMD-mediated pore formation for HCC treatment.
FOXP3 exon 2 controls T
reg
stability and autoimmunity
Authors: Du Jianguang , Wang Qun , Yang Shuangshuang , Chen Si , Fu Yongyao , Spath Sabine , Domeier Phillip , Hagin David , Anover-Sombke Stephanie , Haouili Maya , Liu Sheng , Wan Jun , Han Lei , Liu Juli , Yang Lei , Sangani Neel , Li Yujing , Lu Xiongbin , Janga Sarath Chandra , Kaplan Mark H. , Torgerson Troy R. , Ziegler Steven F. , Zhou Baohua
Published: June 2022

Differing from the mouse
Foxp3
gene that encodes only one protein product, human
FOXP3
encodes two major isoforms through alternative splicing—a longer isoform (FOXP3 FL) containing all the coding exons and a shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans, yet their differences in controlling regulatory T cell phenotype and functionality remain unclear. In this study, we show that patients expressing only the shorter isoform fail to maintain self-tolerance and develop immunodeficiency, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome. Mice with
Foxp3
exon 2 deletion have excessive follicular helper T (T
FH
) and germinal center B (GC B) cell responses, and develop systemic autoimmune disease with anti-dsDNA and antinuclear autoantibody production, as well as immune complex glomerulonephritis. Despite having normal suppressive function in in vitro assays, regulatory T cells expressing FOXP3 ΔE2 are unstable and sufficient to induce autoimmunity when transferred into
Tcrb
-deficient mice. Mechanistically, the FOXP3 ΔE2 isoform allows increased expression of selected cytokines, but decreased expression of a set of positive regulators of
Foxp3
without altered binding to these gene loci. These findings uncover indispensable functions of the FOXP3 exon 2 region, highlighting a role in regulating a transcriptional program that maintains T
reg
stability and immune homeostasis.
The 180-km-long Meers-Willow fault system in the Southern Oklahoma Aulacogen: A potential U.S. mid-continent seismic hazard
Authors: Chase Brandon F. , Kolawole Folarin , Atekwana Estella A. , Carpenter Brett M. , Turko Molly , Abdelsalam Mohamed , Finn Carol
Published: June 2022

We integrate new high-resolution aeromagnetic data with seismic reflection data, well logs, satellite remote sensing, and field observations to provide a regional view of buried and exposed structures in the Southern Oklahoma Aulacogen and to assess their potential for future seismicity. Trends ranging from NW–SE to ~E–W, peaking at 330° ± 4.5° and 280° ± 3°, dominate the magnetic lineaments of the Southern Oklahoma Aulacogen, reflecting basement contacts, dikes, and faults, including a previously unmapped ~100-km-long basement fault, which is herein referred to as the Willow fault. The fault disrupts, truncates, and vertically offsets basement-related seismic reflectors and overlying Paleozoic strata up through the Permian reflectors. Surface deformation along the trend includes fault-parallel monoclinal folds, pervasive fractures, and fracture-hosted mud dikes in Permian evaporite units. These structures indicate a Permian or post-Permian reactivation of the fault. Along-strike, the Willow fault connects to the NW-trending, seismically active Meers Fault to comprise the ~180-km-long Meers-Willow fault system, which potentially represents a major seismic hazard along the Southern Oklahoma Aulacogen. Fault slip potential analyses of the mapped potential fault traces show that seismic hazards are elevated where faults have steeper dips. Given some uncertainty in the regional stress state, we also show that hazards along the NW–SE to E–W trending faults vary considerably within the uncertainty range. We propose that the Meers-Willow fault system originated as a Cambrian aulacogen-scale, basement-rooted fault that was later reactivated as a left-lateral strike-slip fault (with ~40 km displacement) during the late Paleozoic Ancestral Rocky Mountain orogeny, highlighting that lateral offset accommodated a major component of deformation during the orogen.
Seismic attenuation tomography of the Sn phase beneath the Turkish-Iranian Plateau and the Zagros mountain belt
Authors: Kaviani Ayoub , Sandvol Eric , Ku Wenfei , Beck Susan L. , Türkelli Niyazi , Özacar A. Arda , Delph Jonathan R.
Published: June 2022

The Turkish-Iranian Plateau and the Zagros highlands are among the most prominent physiographic features in the Middle East and were formed as a result of continental collision between the Arabian and Eurasian plates. To better understand the nature of the lithospheric mantle and the origin of the observed seismic anomalies in this region, we investigated seismic attenuation of the uppermost mantle by detailed measurements of the quality factor of the Sn seismic phase (Sn Q). To that end, we collected a large data set consisting of 30 years (1990–2020) of waveforms recorded by 1266 permanent and temporary seismic stations, applying both the two-station method (TSM) and reverse two-station method (RTM) to measure path-averaged Sn Q. Finally, we performed a tomographic inversion on the path-averaged Sn Q to map the lateral variations of the upper-mantle attenuation across the northern Middle East. Our Sn attenuation maps show moderately low Q (<250) values beneath the Turkish-Iranian Plateau and high Q values (>350) beneath the Zagros and northern edge of the Arabian plate. Furthermore, our Sn Q model is broadly consistent with seismic velocity models in the region suggesting that most of the seismic anomalies are the result of thermal rather than compositional effects.
Composition and Preparation Method of Rhenium- and Tungsten-Containing Porous Ceramic Converters Influence on the Cumene Dehydrogenation to α-Methylstyrene Process Specific Features
Authors: Fedotov A. S. , Bagdatov R. A. , Grachev D. Yu. , Uvarov V. I. , Kapustin R. D. , Alymov M. I. , Paul S. , Tsodikov M. V.
Published: June 2022

The latest research results on the specific features of the process of cumene dehydrogenation to α-methylstyrene (AMS) on the porous ceramic catalytic converters were presented. The influence of the method of formation of the mono- and bimetallic rhenium- and tungsten-based components on the activity and selectivity of the synthesized converters was evaluated. It was found that the monometallic tungsten-containing converter obtained by combining self-propagating high-temperature synthesis (SHS) with the sol-gel process has the optimal composition. The experiments showed that, for this converter, the temperature range of effective operation is 550–600°C. In this range the space-time yield of AMS reached 14% at a maximum productivity of 20.57 g h–1 dm–3. The degree of carburization of the sample after 6 h of the experiment did not exceed 5 wt %, indicating its high resistance against coking.
Recent information on test utilization and intraindividual change in anti-glutamic acid decarboxylase antibody in Korea: a retrospective study
Authors: Choi Rihwa , Park Wonseo , Chun Gayoung , Lee Jiwon , Lee Sang Gon , Lee Eun Hee
Published: June 2022

Introduction

This study aimed to evaluate the test utilization and intraindividual changes of anti-glutamic acid decarboxylase antibody (GADA), a biomarker for autoimmune diabetes in Korean adults.

Research design and methods

We retrospectively investigated longitudinally measured GADA test results to assess test utilization and intraindividual changes through a laboratory information system.

Results

During the 3-year study period, 11 668 GADA tests were performed in 11 184 Korean adults. The overall rate of GADA positivity at initial measurement was 7.8%. Among the 11 668 test results, 871 GADA test results from 401 Korean patients (228 men and 173 women) requested by 54 hospitals were analyzed for intraindividual changes. Among these 401 patients, 80 (20.0%) had positive (≥2.0 U/mL) and 35 (8.7%) had gray zone GADA (1.0–1.9 U/mL) level at initial measurement. The prevalence of GADA-positive patients based on initial measurement was significantly different by type of medical institution. Among 80 patients with initial positive results, 5 (6.3%) experienced qualitative GADA changes during follow-up. Among the 321 patients with initially negative or gray zone GADA, 9 (2.8%) changed to GADA positive at least once during follow-up.

Conclusions

Although most patients had stable GADA results, some exhibited qualitative changes during follow-up. This study can help to understand the variation in GADA positivity in the monitored patients.
Experience of field testing in Lebanon during the COVID-19 pandemic, January to August 2021
Authors: Farah Zeina , Ghosn Nada , Tohme Tatiana , Abou Naja Hala , Abdel Malak Reem , Sweidan Hawraa , Hassan Hamad
Published: June 2022

Soon after detection of the first COVID-19 case in Lebanon, a testing strategy was developed aiming to early detect new cases and identify close contacts in order to implement isolation and quarantine measures, thus limiting disease transmission. Field-testing activities were initiated in March 2020, focusing on suspected cases and close contacts. The objective of this paper is to present data collected between the 1st and the 35th week of 2021 and discuss challenges and lessons learned. During the study period, testing activities were conducted in field sites covering all Lebanese districts and following a fixed schedule. Testing was provided free of charge for suspected/probable patients with COVID-19 and close contacts of positive cases. Nasopharyngeal specimens were collected and sent to designated laboratories for reverse transcription polymerase chain reaction testing. Results were received on a timely manner, within 48 hours. From the 1st to the 35th week of 2021, 1244 field-testing activities were conducted with an average of 37 testing activities per week. During this period, 71 542 samples were collected with an average of 2104 specimens per week. On average, activities covered 78% of the Lebanese districts. The average positivity rate for this period was 24% (15%–33%) in line with the virus circulation levels in the country. Timely development and implementation of a testing strategy is crucial during epidemics. The success of Lebanon’s field-testing experience was mainly due to the timely adapted approach that covered all national territories, targeting all residents as well as high-risk groups in suburbs and remote areas.
Psychometric properties of self-reported financial toxicity measures in cancer survivors: a systematic review
Authors: Zhu Zheng , Xing Weijie , Wen Huan , Sun Yanling , So Winnie K W , Lizarondo Lucylynn , Peng Jian , Hu Yan
Published: June 2022

Objective

The aim of this systematic review was to summarise the psychometric properties of patient-reported outcome measures (PROMs) measuring financial toxicity (FT) in cancer survivors.

Design

This systematic review was conducted according to the guidance of the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology.

Data sources

Comprehensive searches were performed in PubMed, MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, ProQuest and Cochrane Library from database inception to February 2022.

Eligibility criteria for selecting studies

We included studies that reported any PROMs for measuring FT in cancer survivors who were ≥18 years old. FT was defined as perceived subjective financial distress resulting from objective financial burden. Studies that were not validation studies and that used a PROM only as an outcome measurement were excluded.

Data extraction and synthesis

Two reviewers independently extracted data from the included papers. We used the COSMIN criteria to summarise and evaluate the psychometric properties of each study regarding structural validity, internal consistency, reliability, measurement error, hypothesis testing for construct validity, cross-cultural validity/measurement invariance, criterion validity and responsiveness.

Results

A total of 23 articles (21 PROMs) were eligible for inclusion in this study. The findings highlighted that the Comprehensive Score for Financial Toxicity (COST) had an adequate development process and showed better psychometric properties than other PROMs, especially in internal consistency (Cronbach’s α=0.92), reliability (intraclass correlation coefficient=0.80) and hypothesis testing (r=0.42–0.20).

Conclusions

From a psychometric property perspective, the COST could be recommended as the most suitable worldwide available measure for use in research and clinical practice across different contexts. We suggest that PROMs should be selected only after careful consideration of the local socioeconomic context. Future studies are warranted to develop various FT PROMs based on different social and cultural backgrounds and to clarify the theoretical grounds for assessing FT.
Bearberry in the treatment of acute uncomplicated cystitis (BRUMI): protocol of a multicentre, randomised double-blind clinical trial
Authors: Tóth Barbara , Jávorházy András , Nyirády Péter , Csupor-Löffler Boglárka , Birinyi Péter , Zhanel George , Naber Kurt , Länger Reinhard , Vörhendi Nóra , Gede Noémi , Váncsa Szilárd , Hegyi Péter , Csupor Dezső
Published: June 2022

Background

Bearberry (Arctostaphylos uva-ursi) leaf is available as a treatment of uncomplicated cystitis in several European countries. The antimicrobial activity of its extracts and some of its individual constituents has been observed in vitro; however, the efficacy of bearberry compared with standard antimicrobial therapy has not been assessed yet.

Objective

The objective of the study is to assess the safety and non-inferiority of bearberry as an alternative therapy in the treatment of acute uncomplicated cystitis in comparison with standard antibiotic therapy (fosfomycin).

Methods and analysis

This is a randomised controlled double-blinded multicentre trial. Eligible patients will be premenopausal women with a sum score of ≥6 for the typical acute uncomplicated cystitis symptoms (frequency, urgency, painful urination, incomplete emptying, suprapubic pain and visible haematuria) reported on the Acute Cystitis Symptom Score (ACSS) typical domain and pyuria. Patients will be randomly assigned to receive 3 g single dose of fosfomycin powder and two placebo tablets three times a day for 7 days or B a single dose of placebo powder and two tablets containing a dry extract of Uvae ursi folium. At least 504 patients (allocated as 1:1) will need to be enrolled to access non-inferiority with a non-inferiority limit of 14% for the primary endpoint.

Improvement of symptoms of uncomplicated cystitis (based on the ACSS score) at day 7 is defined as the primary endpoint, whereas several secondary endpoints such as the number and ratio of patients with bacteriuria at day 7, frequency and severity of side effects; recurrence of urinary tract infection, concurrent use of other over the counter (OTC) medications and food supplements will be determined to elucidate more detailed differences between the groups. The number of recurrences and medications taken for treatment will be monitored for a follow-up period of 90 days (80–100 days).

Ethics and dissemination

This study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/4225-1/2021/EKU). The results will be disseminated by publication of peer-reviewed manuscripts.

Trial registration number

NCT05055544.
Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial
Authors: Mundell Niamh L , Owen Patrick J , Dalla Via Jack , Macpherson Helen , Daly Robin M , Livingston Patricia M , Rantalainen Timo , Foulkes Stephen J , Millar Jeremy L , Murphy Declan G , Fraser Steve F
Published: June 2022

Objectives

The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT).

Design

12-month, two-arm, randomised controlled trial.

Setting

University clinical exercise centre.

Participants

70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36).

Intervention

Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation.

Primary and secondary outcome measures

Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%).

Results

Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%–82%) and 91% (66%–97%), respectively. Ex + Suppl had no effect on cognition at any time.

Conclusions

A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer.

Trial registration number

Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).
Economic evaluations of audit and feedback interventions: a systematic review
Authors: Moore Lynne , Guertin Jason Robert , Tardif Pier-Alexandre , Ivers Noah Michael , Hoch Jeffrey , Conombo Blanchard , Antony Jesmin , Stelfox Henry Thomas , Berthelot Simon , Archambault Patrick , Turgeon Alexis , Gandhi Rohit , Grimshaw JM
Published: June 2022

Background

The effectiveness of audit and feedback (A&F) interventions to improve compliance to healthcare guidelines is supported by randomised controlled trials (RCTs) and meta-analyses of RCTs. However, there is currently a knowledge gap on their cost-effectiveness.

Objective

We aimed to assess whether A&F interventions targeting improvements in compliance to recommended care are economically favourable.

Methods

We conducted a systematic review including experimental, observational and simulation-based economic evaluation studies of A&F interventions targeting healthcare providers. Comparators were a ‘do nothing’ strategy, or any other intervention not involving A&F or involving a subset of A&F intervention components. We searched MEDLINE, CINAHL, CENTRAL, Econlit, EMBASE, Health Technology Assessment Database, MEDLINE, NHS Economic Evaluation Database, ABI/INFORM, Web of Science, ProQuest and websites of healthcare quality associations to December 2021. Outcomes were incremental cost-effectiveness ratios, incremental cost-utility ratios, incremental net benefit and incremental cost-benefit ratios. Pairs of reviewers independently selected eligible studies and extracted relevant data. Reporting quality was evaluated using CHEERS (Consolidated Health Economic Evaluation Reporting Standards). Results were synthesised using permutation matrices for all studies and predefined subgroups.

Results

Of 13 221 unique citations, 35 studies met our inclusion criteria. The A&F intervention was dominant (ie, at least as effective with lower cost) in 7 studies, potentially cost-effective in 26 and was dominated (ie, the same or less effectiveness and higher costs) in 2 studies. A&F interventions were more likely to be economically favourable in studies based on health outcomes rather than compliance to recommended practice, considering medical costs in addition to intervention costs, published since 2010, and with high reporting quality.

Discussion

Results suggest that A&F interventions may have a high potential to be cost-effective. However, as is common in systematic reviews of economic evaluations, publication bias could have led to an overestimation of their economic value.
Impact of different climatic conditions on peak core temperature of elite athletes during exercise in the heat: a Thermo Tokyo simulation study
Authors: Teunissen Lennart P J , Jansen Kaspar M B , Janssen Emiel , Kingma Boris R M , de Korte Johannus Q , Eijsvogels Thijs M H
Published: June 2022

Objectives

To evaluate how separate and combined climatic parameters affect peak core temperature during exercise in the heat using computer simulations fed with individual data.

Methods

The impact of eight environmental conditions on rectal temperature (Tre) was determined for exercise under heat stress using the Fiala-thermal-Physiology-and-Comfort simulation model. Variations in ambient temperature (Ta±6°C), relative humidity (RH±15%) and solar radiation (SR+921 W/m2) were assessed in isolation and combination (worst-case/best-case scenarios) and compared with baseline (Ta32°C, RH 75%, SR 0 W/m2). The simulation model was fed with personal, anthropometric and individual exercise characteristics.

Results

54 athletes exercised for 46±10 min at baseline conditions and achieved a peak core temperature of 38.9±0.5°C. Simulations at a higher Ta(38°C) and SR (921 W/m2) resulted in a higher peak Trecompared with baseline (+0.6±0.3°C and +0.5±0.2°C, respectively), whereas a higher RH (90%) hardly affected peak Tre(+0.1±0.1°C). A lower Ta(26°C) and RH (60%) reduced peak Treby −0.4±0.2°C and a minor −0.1±0.1°C, respectively. The worst-case simulation yielded a 1.5±0.4°C higher Trethan baseline and 2.0±0.7°C higher than the best-case condition.

Conclusion

Combined unfavourable climatic conditions produce a greater increase in peak core temperature than the sum of its parts in elite athletes exercising in the heat.
Lessons from an audit of exclusive enteral nutrition in adult inpatients and outpatients with active Crohn’s disease: a single-centre experience
Authors: Melton Sarah L , Fitzpatrick Jessica A , Taylor Kirstin M , Halmos Emma P , Gibson Peter R
Published: June 2022

Objective

To evaluate clinical outcomes, patterns of use, tolerance and nutritional outcomes of exclusive enteral nutrition (EEN) in adults with Crohn’s disease and to compare initiation in the inpatient compared with ambulatory care setting.

Design/method

Adults with Crohn’s disease who received EEN at a single centre over 2.5 years were identified and outcomes assessed via examination of patient records.

Results

EEN was initiated in 60 patients (23 as an outpatient) who had objective evidence of active disease. Of 49 in whom the goal was induction of remission, 28 completed EEN and 24 achieved clinical remission/response. Twenty-one withdrew prematurely, due to intolerance in 15 and disease factors in 6. Of 11 with a planned intervention, 6 fulfilled the goal of downstaging disease while two were intolerant. Completion of the prescribed therapy was associated with self-reported adherence to EEN and with improvements in disease activity scores and biochemical markers. Malnutrition halved (40% to 20%) and intentional weight loss (median 5.1 kg) was achieved in six obese patients. The major reason for intolerance was the inability to accept total avoidance of non-formula food. There were no differences in any outcomes according to the location of initiation of therapy.

Conclusion

Positive outcomes occur in 70% of adult patients with Crohn’s disease tolerating EEN and 81% in those who are able to completely adhere to EEN, without compromise of nutritional status. Similar success occurs when initiated as an inpatient or outpatient. Failure to tolerate EEN is the major hurdle to its use.
Activation of NOTCH signaling via DLL1 is mediated by APE1-redox-dependent NF-κB activation in oesophageal adenocarcinoma
Authors: Chen Lei , Lu Heng , Peng Dunfa , Cao Long Long , Ballout Farah , Srirmajayam Kannappan , Chen Zheng , Bhat Ajaz , Wang Timothy C , Capobianco Anthony , Que Jianwen , McDonald Oliver Gene , Zaika Alexander , Zhang Shutian , El-Rifai Wael
Published: June 2022

Objective

Oesophageal adenocarcinoma (EAC) arises in the setting of Barrett’s oesophagus, an intestinal metaplastic precursor lesion that can develop in patients with chronic GERD. Here, we investigated the role of acidic bile salts, the mimicry of reflux, in activation of NOTCH signaling in EAC.

Design

This study used public databases, EAC cell line models, L2-IL1β transgenic mouse model and human EAC tissue samples to identify mechanisms of NOTCH activation under reflux conditions.

Results

Analysis of public databases demonstrated significant upregulation of NOTCH signaling components in EAC. In vitro studies demonstrated nuclear accumulation of active NOTCH1 cleaved fragment (NOTCH intracellular domain) and upregulation of NOTCH targets in EAC cells in response to reflux conditions. Additional investigations identified DLL1 as the predominant ligand contributing to NOTCH1 activation under reflux conditions. We discovered a novel crosstalk between APE1 redox function, reflux-induced inflammation and DLL1 upregulation where NF-κB can directly bind to and induce the expression of DLL1. The APE1 redox function was crucial for activation of the APE1-NF-κB-NOTCH axis and promoting cancer cell stem-like properties in response to reflux conditions. Overexpression of APE1 and DLL1 was detected in gastro-oesophageal junctions of the L2-IL1ß transgenic mouse model and human EAC tissue microarrays. DLL1 high levels were associated with poor overall survival in patients with EAC.

Conclusion

These findings underscore a unique mechanism that links redox balance, inflammation and embryonic development (NOTCH) into a common pro-tumorigenic pathway that is intrinsic to EAC cells.
Gene expression profiles of ischemic stroke clots retrieved by mechanical thrombectomy are associated with disease etiology
Authors: Tutino Vincent M , Fricano Sarah , Chien Aichi , Patel Tatsat R , Monteiro Andre , Rai Hamid H , Dmytriw Adam A , Chaves Lee D , Waqas Muhammad , Levy Elad I , Poppenberg Kerry E , Siddiqui Adnan H
Published: June 2022

Background

Determining stroke etiology is crucial for secondary prevention, but intensive workups fail to classify ~30% of strokes that are cryptogenic.

Objective

To examine the hypothesis that the transcriptomic profiles of clots retrieved during mechanical thrombectomy are unique to strokes of different subtypes.

Methods

We isolated RNA from the clots of 73 patients undergoing mechanical thrombectomy. Samples of sufficient quality were subjected to 100-cycle, paired-end RNAseq, and transcriptomes with less than 10 million unique reads were excluded from analysis. Significant differentially expressed genes (DEGs) between subtypes (defined by the Trial of Org 10 172 in Acute Stroke Treatment) were identified by expression analysis in edgeR. Gene ontology enrichment analysis was used to study the biologic differences between stroke etiologies.

Results

In all, 38 clot transcriptomes were analyzed; 6 from large artery atherosclerosis (LAA), 21 from cardioembolism (CE), 5 from strokes of other determined origin, and 6 from cryptogenic strokes. Among all comparisons, there were 816 unique DEGs, 174 of which were shared by at least two comparisons, and 20 of which were shared by all three. Gene ontology analysis showed that CE clots reflected high levels of inflammation, LAA clots had greater oxidoreduction and T-cell processes, and clots of other determined origin were enriched for aberrant platelet and hemoglobin-related processes. Principal component analysis indicated separation between these subtypes and showed cryptogenic samples clustered among several different groups.

Conclusions

Expression profiles of stroke clots were identified between stroke etiologies and reflected different biologic responses. Cryptogenic thrombi may be related to multiple etiologies.
Quantifying and characterising tobacco content in the most in-demand streamed series in 10 low/middle-income countries in 2019
Authors: Fitzpatrick Iona , Byrne Danielle , Gilmore Anna B , Hasan Farheen , Cranwell Joanne
Published: June 2022

Background

In line with the Framework Convention for Tobacco Control (FCTC) Article 13, the advertising and promotion of tobacco products is increasingly restricted. However, popular media continues to pose an exposure risk to youth populations (aged 13–18 years), including in low/middle-income countries (LMICs). This study presents a novel method to record the prevalence of tobacco depictions in streamed media content and the characterisation of that content.

Objectives

Evaluate the frequency and characterisation of tobacco depictions in streamed content in LMICs.

Methods

Presence of tobacco depictions was evaluated in the four most in-demand series across 10 LMICs for the year 2019; this list included series that were released from 2017 onwards (2017–2019). Each character identified using tobacco was coded against 13 characterisation variables that recorded key demographic information as well as contextual information.

Results

The majority of series (72%, 13 of 18) analysed contained at least one depiction of tobacco use. 38% of tobacco depictions (359 of 941) occurred in content deemed suitable for audiences aged 15 years and up. 113 characters were depicted using tobacco across 38 episodes. ‘Star’ actors, featuring in opening credits with active profiles on the Internet Movie Database, accounted for 73% of tobacco-using characters (83 of 113). 5% of characters depicted using tobacco (6 of 113) were coded as minors (under 18 years).

Conclusion

The continued prevalence of positively characterised tobacco content in youth-focused streamed content that is in high demand in LMICs poses a risk as a driver of smoking uptake in youth populations. There is an urgent need to better enforce tobacco advertising, promotion and sponsorship legislation in LMICs, and to update WHO FCTC guidance in line with rapidly evolving media platforms and content that is available internationally.
Algal responses to metal(loid) pollution, urbanization, and climatic changes in subarctic lakes around Yellowknife, Canada
Authors: Sivarajah Branaavan , Korosi Jennifer B. , Thienpont Joshua R. , Kimpe Linda E. , Blais Jules M. , Smol John P.
Published: June 2022

The lakes around Yellowknife (Northwest Territories, Canada) have been impacted by multiple environmental stressors throughout the 20th and early 21st centuries. Here, we have synthesized diatom assemblage data from ten lake sediment cores from the Yellowknife area and used a landscape-scale paleolimnological approach to investigate the cumulative impacts of past gold mining activities, urbanization, and climate warming on aquatic biota. Our investigations indicated that diatom species turnover (measured using detrended canonical correspondence analysis) was highest at lakes closer to the city and mines, as these sites were more severely impacted by land-use changes (e.g., sewage disposal, run-off from waste disposal sites) and roaster stack emission from the gold mines. Diatom assemblage shifts indicative of climate-induced changes to lake thermal properties were also observed across the gradient of human activities. The inclusion of remote sites was useful to disentangle the effects of climate-mediated changes from impacts related to mining and urbanization. This investigation suggests that the diatom assemblages of the lakes around Yellowknife have changed markedly over the last ∼80 years and there are no signs of biological recovery since the cessation of mining activities around the turn of the 21st century. The biota of the subarctic lakes around Yellowknife are now strongly influenced by climate-mediated changes to lake thermal properties and the urban lakes are also influenced by the legacies of past land-use changes.
The power of multi-matrix monitoring in the Pan-Arctic region: plastics in water and sediment
Authors: Martin Jake , Granberg Maria , Provencher Jennifer F. , Liborion Max , Pijogge Liz , Magnusson Kerstin , Hallanger Ingeborg G. , Bergmann Melanie , Aliani Stefano , Gomiero Alessio , Grøsvik Bjørn Einar , Vermaire Jesse , Primpke Sebastian , Lusher Amy L.
Published: June 2022

Litter and microplastic assessments are being carried out worldwide. Arctic ecosystems are no exception and plastic pollution is high on the Arctic Council's agenda. Water and sediment have been identified as two of the priority compartments for monitoring plastics under the Arctic Monitoring and Assessment Programme (AMAP). Recommendations for monitoring both compartments are presented in this publication. Alone, such samples can provide information on presence, fate, and potential impacts to ecosystems. Together, the quantification of microplastics in sediment and water from the same region produce a three-dimensional picture of plastics, not only a snapshot of floating or buoyant plastics in the surface water or water column but also a picture of the plastics reaching the shoreline or benthic sediments, in lakes, rivers, and the ocean. Assessment methodologies must be adapted to the ecosystems of interest to generate reliable data. In its current form, published data on plastic pollution in the Arctic is sporadic and collected using a wide spectrum of methods which limits the extent to which data can be compared. A harmonised and coordinated effort is needed to gather data on plastic pollution for the Pan-Arctic. Such information will aid in identifying priority regions and focusing mitigation efforts.
Gamma, X-ray, and neutron shielding properties of silicon–germanium alloys
Authors: Sathish K.V. , Manjunatha H.C. , Vidya Y.S. , Seenappa L. , Sridhar K.N. , Gupta P.S. Damodara , Raj Alfred Cecil
Published: June 2022

This work focuses on the gamma/X-ray and neutron shielding properties of silicon–germanium alloys in different compositions such as Si0.1Ge0.9 (SG1), Si0.2Ge0.8, Si0.4Ge0.6, Si0.6Ge0.4, Si0.8Ge0.2, and Si0.9Ge0.1. Among all the selected alloys, SG1 has less half-value thickness, tenth-value thickness, and penetration depth, whereas specific gamma-ray constant, Zeff, electron density, radiation protection efficiency, and kinetic energy released in matter have larger values compared to the other studied alloys. The neutron shielding parameters, such as coherent neutron scattering length, incoherent neutron scattering length, coherent neutron scattering cross-section, and incoherent neutron scattering cross-sections are smaller for the SG1 alloy than the other studied alloys. Furthermore, total neutron scattering cross-section and neutron absorption cross-section are found to be larger for SG1 than the other studied alloys. Based on gamma/X-ray and neutron shielding parameter analysis, we have suggested a shielding material consisting of ordinary concrete and SG1 alloy of particular thickness to cease X-ray/gamma-ray and neutron radiation. By analyzing all these parameters, we suggest that the SG1 alloy might be a good shielding material for X-rays/gamma-rays and for neutrons compared to other selected alloys.
Solutions of the Dirac equation with position-dependent mass for q-deformed Pöschl–Teller and Coulomb-like tensor potentials
Authors: Bouledjedj S. , Khodja A. , Benamira F. , Guechi L.
Published: June 2022

We consider the Dirac equation with position-dependent mass for a q-deformed Pöschl–Teller potential plus a Coulomb-like tensor interaction in the limits of spin and pseudospin symmetries. Under the condition of spin symmetry, the bound state energy eigenvalue equation and the two radial components of the Dirac wave function in terms of the Jacobi polynomials are obtained approximately for an arbitrary shifted spin-orbit quantum number λκ = κ + H and for any value of the deformation parameter q ≥ 1. In the case of the pseudospin symmetry limit, there are no bound states. The Dirac equation describes a free physical system and the two components of the wave function are expressed in terms of the spherical Bessel functions.
Noether symmetry approach in non-minimal derivative coupling gravity
Authors: Dolohtahe Muhammadsorfee , Srikom Watcharakorn , Channuie Phongpichit , Kaewkhao Narakorn
Published: June 2022

In this work, we examine solutions of the system of equations obtained by applying the Noether gauge symmetry (NGS) and its conserved quantity for the standard general relativity (GR) and the non-minimal derivative coupling (NMDC) cosmological model. We discover two salient features of the solutions. The first one is $$a(t)\propto t^{1/3}$$

a

(
t
)

∝

t

1
/
3

for a kinetic-dominant phase which may emerge before inflationary period at very early time for GR case. The second one is a new form of scalar field $$\phi (t)$$

ϕ
(
t
)

govern by the exponential cosmological solution for NMDC case, $$\phi (t)=(c_{1}+c_{2}t)e^{-\lambda t}+c_{3}$$

ϕ

(
t
)

=

(

c
1

+

c
2

t
)

e

-
λ
t

+

c
3

.
Derivation of the two Schwarzians effective action for the Sachdev–Ye-Kitaev spectral form factor
Authors: Cardella Matteo A.
Published: June 2022

The Sachdev–Ye-Kitaev model spectral form factor exhibits absence of information loss, in the form of a ramp and a plateau that are typical in random matrix theory. In a large N collective fields description, the ramp was reproduced by Saad et al. (A semiclassical ramp in SYK and in gravity, arXiv:1806.06840) by replica symmetry breaking saddles. We derive a two sides Schwarzians effective action for fluctuations around the ramp critical saddles, by computing responses to a smeared version of the two replica kinetic kernel. Our result confirms [1], where the form of the action was heuristically guessed by indirect arguments supported by numerical evidences.
Minimally deformed charged stellar model by gravitational decoupling in 5D Einstein–Gauss–Bonnet gravity
Authors: Maurya S. K. , Banerjee Ayan , Pradhan Anirudh , Yadav Dhananjay
Published: June 2022

We investigate the possibility of existing a class of compact charged spheres made of a charged perfect fluid in the framework of Einstein–Gauss–Bonnet theory in five-dimensional spacetime (5D EGB). In order to study spherically symmetric compact stars in EGB gravity, we prefer to apply a systematic and direct approach to decoupling gravitational sources via the minimal geometric deformation approach (MGD), which allows us to prove that the fluid must be anisotropic. In fact, we specify a well-known Krori–Barua spacetime in the MGD approach that helps us to determine the decoupling sector completely. Indeed, by using this approach, we found an exact and physically acceptable solution which satisfies all the elementary criteria of physical acceptability for a stellar solution via mimic approach. Finally, we show that the compactness factor in the presence of gravitational decoupling satisfies the Buchdahal limit under 5D EGB gravity.
A machine learning-based methodology for pulse classification in dual-phase xenon time projection chambers
Authors: Brás P. , Neves F. , Lindote A. , Cottle A. , Cabrita R. , Asamar E. Lopez , Pereira G. , Silva C. , Solovov V. , Lopes M. I.
Published: June 2022

Machine learning techniques are now well established in experimental particle physics, allowing detector data to be analyzed in new and unique ways. The identification of signals in particle observatories is an essential data processing task that can potentially be improved using such methods. This paper aims at exploring the benefits that a dedicated machine learning approach might provide to the classification of signals in dual-phase noble gas time projection chambers. A full methodology is presented, from exploratory data analysis using Gaussian mixture models and feature importance ranking to the construction of dedicated predictive models based on standard implementations of neural networks and random forests, validated using unlabeled simulated data from the LZ experiment as a proxy to real data. The global classification accuracy of the predictive models developed in this work is estimated to be >99.0%, which is an improvement over conventional algorithms tested with similar data. The results from the clustering analysis were also used to identify anomalies in the data caused by miscalculated signal properties, showing that this methodology can also be used for data monitoring.