bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volume sweep imaging lung teleultrasound for detection of COVID-19 in Peru: a multicentre pilot study
Authors: Marini Thomas J , Kaproth-Joslin Katherine , Ambrosini Robert , Baran Timothy M , Dozier Ann M , Zhao Yu T , Satheesh Malavika , Mahony Reátegui-Rivera Christian , Sifuentes Walter , Rios-Mayhua Gloria , Castaneda Benjamin 
Published: October 2022

ObjectivesPulmonary disease is a significant cause of morbidity and mortality in adults and children, but most of the world lacks diagnostic imaging for its assessment. Lung ultrasound is a portable, low-cost, and highly accurate imaging modality for assessment of pulmonary pathology including pneumonia, but its deployment is limited secondary to a lack of trained sonographers. In this study, we piloted a low-cost lung teleultrasound system in rural Peru during the COVID-19 pandemic using lung ultrasound volume sweep imaging (VSI) that can be operated by an individual without prior ultrasound training circumventing many obstacles to ultrasound deployment.DesignPilot study.SettingStudy activities took place in five health centres in rural Peru.ParticipantsThere were 213 participants presenting to rural health clinics.InterventionsIndividuals without prior ultrasound experience in rural Peru underwent brief training on how to use the teleultrasound system and perform lung ultrasound VSI. Subsequently, patients attending clinic were scanned by these previously ultrasound-naïve operators with the teleultrasound system.Primary and secondary outcome measuresRadiologists examined the ultrasound imaging to assess its diagnostic value and identify any pathology. A random subset of 20% of the scans were analysed for inter-reader reliability.ResultsLung VSI teleultrasound examinations underwent detailed analysis by two cardiothoracic attending radiologists. Of the examinations, 202 were rated of diagnostic image quality (94.8%, 95% CI 90.9% to 97.4%). There was 91% agreement between radiologists on lung ultrasound interpretation among a 20% sample of all examinations (κ=0.76, 95% CI 0.53 to 0.98). Radiologists were able to identify sequelae of COVID-19 with the predominant finding being B-lines.ConclusionLung VSI teleultrasound performed by individuals without prior training allowed diagnostic imaging of the lungs and identification of sequelae of COVID-19 infection. Deployment of lung VSI teleultrasound holds potential as a low-cost means to improve access to imaging around the world.
Cross-sectional association between prolactin levels and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: a retrospective analysis of patients from a single hospital in China
Authors: Zhang Yuanyuan , Liu Huaizhen 
Published: October 2022

ObjectiveThis study aimed to retrospectively assess the association between prolactin (PRL) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).Design and settingA retrospective, cross-sectional study was conducted at a single hospital in Anhui, China.ParticipantsA total of 406 patients with T2DM (230 men and 176 women) was included.Outcome measuresP values for the independent t-test, the Mann-Whitney rank-sum test, the Spearman correlation analysis and multiple logistic regression models were used to explore the association between PRL and NAFLD in patients with T2DM.ResultsThe results indicated that in both men and women, the levels of PRL were significantly lower in the T2DM with NAFLD group than in the T2DM without NAFLD group (men: 9.56 ng/mL vs 10.36 ng/mL, women: 10.38 ng/mL vs 12.97 ng/mL). In male patients, the levels of PRL were negatively correlated with hip circumference (r=−0.141, p=0.032), homoeostasis model assessment for insulin resistance (C-peptide) (r=−0.141, p=0.032) and triglyceride (TG) (r=−0.252, p=0.000) values and inversely correlated with high-density lipoprotein (r=0.147, p=0.025) levels. In female patients, PRL levels were negatively related to body mass index (r=−0.192, p=0.011), diastolic blood pressure (r=−0.220, p=0.003), waist circumference (r=−0.152, p=0.044), hip circumference (r=−0.157, p=0.037) and TG (r=−0.258, p=0.001) values. Logistic regression analysis revealed a negative relationship between PRL and NAFLD (men: OR 0.891, 95% CI 0.803 to 0.989, p=0.031; women: OR 0.874, 95% CI 0.797 to 0.957, p=0.004). As PRL levels increased, NAFLD prevalence decreased in both sexes (men: p=0.012, women: p=0.013).ConclusionOur results suggest that low levels of PRL in the physiological range were markers of NAFLD in patients with T2DM and that PRL within the biologically high range may play a protective role in the pathogenesis of NAFLD.
The role of teams in shaping quality of obstetrical care: a cross-sectional study in Dire Dawa, Ethiopia
Authors: Gage Anna D , Yakob Bereket , McConnell Margaret , Girma Tsinuel , Damtachew Brook , Bauhoff Sebastian , Kruk Margaret E 
Published: October 2022

ObjectivesTo examine how characteristics of clinical colleagues influence quality of care.DesignWe conducted a cross-sectional observational study examining the associations between quality of care and a provider’s coworkers, controlling for individual provider’s characteristics and contextual factors.SettingNine health facilities in Dire Dawa Administration, Ethiopia, from December 2020 to February 2021.Participants824 clients and 95 unique providers were observed across the 9 health facilities.Outcome measuresWe examine the quality of processes of intrapartum and immediate postpartum care during five phases of the delivery (first examination, first stage of labour, third stage of labour, immediate newborn care and immediate maternal postpartum care).ResultsFor the average client, 50% of the recommended routine clinical actions were completed during the delivery overall, with immediate maternal postpartum care being the least well performed (17% of recommended actions). Multiple healthcare providers were involved in 55% of deliveries. The number of providers contributing to a delivery was unassociated with the quality of care, but a one standard deviation increase in the coworker’s performance was associated with a 2% point increase in quality of care (p<0.01); this association was largest among providers in the middle quartiles of performance.ConclusionsA provider’s typical performance had a modest positive association with quality of delivery care given by their coworker. As delivery care is often provided by multiple healthcare providers, examining the dynamics of how they influence one another can provide important insights for quality improvement.
METRIC-EF: magnetic resonance enterography to predict disabling disease in newly diagnosed Crohn’s disease—protocol for a multicentre, non-randomised, single-arm, prospective study
Authors: Kumar Shankar , Plumb Andrew , Mallett Sue , Bhatnagar Gauraang , Bloom Stuart , Clarke Caroline S , Hamlin John , Hart Ailsa L , Jacobs Ilan , Travis Simon , Vega Roser , Halligan Steve , Taylor Stuart Andrew 
Published: October 2022

IntroductionCrohn’s disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis.Methods and analysisWe describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis.Ethics and disseminationThis study protocol achieved National Health Service Research Ethics Committee (NHS REC), London—Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications.Trial registration numberISRCTN76899103.
NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures
Authors: Hsu Nai-Yun , Nayar Shikha , Gettler Kyle , Talware Sayali , Giri Mamta , Alter Isaac , Argmann Carmen , Sabic Ksenija , Thin Tin Htwe , Ko Huai-Bin Mabel , Werner Robert , Tastad Christopher , Stappenbeck Thaddeus , Azabdaftari Aline , Uhlig Holm H , Chuang Ling-Shiang , Cho Judy H 
Published: October 2022

ObjectiveLoss-of-function mutations in genes generating reactive oxygen species (ROS), such asNOX1, are associated with IBD. Mechanisms whereby loss of ROS drive IBD are incompletely defined.DesignROS measurements and single-cell transcriptomics were performed on colonoids stratified byNOX1genotype and TNFα stimulation. Clustering of epithelial cells from human UC (inflamed and uninflamed) scRNASeq was performed. Validation of M cell induction was performed by immunohistochemistry using UEA1 (ulex europaeus agglutin-1 lectin) and in vivo with DSS injury.ResultsTNFα induces ROS production more in NOX1-WT versus NOX1-deficient murine colonoids under a range of Wnt-mediated and Notch-mediated conditions. scRNASeq from inflamed and uninflamed human colitis versus TNFα stimulated, in vitro colonoids defines substantially shared, induced transcription factors; NOX1-deficient colonoids express substantially lower levels of STAT3 (signal transducer and activator of transcription 3), CEBPD (CCAAT enhancer-binding protein delta),DNMT1(DNA methyltransferase) andHIF1A(hypoxia-inducible factor) baseline. Subclustering unexpectedly showed marked TNFα-mediated induction of M cells (sentinel cells overlying lymphoid aggregates) in NOX1-deficient colonoids. M cell induction by UEA1 staining is rescued with H2O2and paraquat, defining extra- and intracellular ROS roles in maintenance of LGR5+ stem cells. DSS injury demonstratedGP2(glycoprotein-2), basal lymphoplasmacytosis and UEA1 induction in NOX1-deficiency. Principal components analyses of M cell genes and decreased DNMT1 RNA velocity correlate with UC inflammation.ConclusionsNOX1 deficiency plus TNFα stimulation contribute to colitis through dysregulation of the stem cell niche and altered cell differentiation, enhancing basal lymphoplasmacytosis. Our findings prioritise ROS modulation for future therapies.
Genetic Variability and Association of Traits in Bread Wheat (Triticum aestivum L.) Genotypes in Gechi District, South West Ethiopia
Authors: Geneti Garome Shifaraw , Kebede Sentayehu Alamerew , Mekonnen Techale Birhan 
Published: October 2022

Bread wheat is the world’s leading cereal grain, and more than one-third of the world’s population uses it as a staple food. The bread wheat production in Ethiopia is low compsssared to the national average yield, mainly due to the lack of high-yielding genotypes. This study was conducted during the 2019-2020 growing season to assess genetic variability and estimate the association of traits among bread wheat genotypes. The experiment consists of 49 bread wheat genotypes and is laid out in 7 × 7 simple lattice designs. The results showed significant differences (

p

< 0.01) among genotypes for most of the studied traits. Moderate genotypic coefficient of variation (GCV) and phenotypic coefficient of variation (PCV) values were estimated for yield plant −1, thousand seed weight, and biomass yield. High heritability coupled with a high GAM was observed for thousand seed weight and yield plant –1. The grain yield showed a highly significant (

p

< 0.01) correlation with many yield-related traits at the phenotypic and genotypic levels. The biomass yield and the harvest index exerted the highest positive direct effect on grain yield at the genotypic level. The highest intercluster distance was observed between clusters I and IV (D2 = 31.86

∗
∗

), followed by clusters II and IV (D2 = 29.21

∗

), and clusters II and III (D2 = 28.24

∗

), which indicated the chance of selecting a member of these clusters for hybridization. This experiment’s result indicates sufficient genetic variability among the tested genotypes, which provides ample scope for selecting superior and desired genotypes. Best-performed genotypes should be included in the future breeding program for further yield improvement. In conclusion, attention should be given to traits with moderate to high heritability and GAM, exerting a positive direct effect on the grain yield. However, the experiment should be repeated over locations and seasons to draw a definite conclusion.
Obesity Programs Macrophages to Support Cancer Progression
Authors: Singh Abhijeet , Mayengbam Shyamananda Singh , Yaduvanshi Himanshi , Wani Mohan R. , Bhat Manoj Kumar 
Published: October 2022

AbstractObesity induces multifactorial effects such as dyslipidemia, insulin resistance, and arterial hypertension that influence the progression of many diseases. Obesity is associated with an increased incidence of cancers, and multiple mechanisms link obesity with cancer initiation and progression. Macrophages participate in the homeostasis of adipose tissue and play an important role in cancer. Adipose tissue expansion in obesity alters the balance between pro- and anti-inflammatory macrophages, which is a primary cause of inflammation. Chronic low-grade inflammation driven by macrophages is also an important characteristic of cancer. Adipocytes secrete various adipokines, including adiponectin, leptin, IL6, and TNFα, that influence macrophage behavior and tumor progression. Furthermore, other metabolic effects of obesity, such as hyperlipidemia, hyperglycemia, and hypercholesterolemia, can also regulate macrophage functionality in cancer. This review summarizes how obesity influences macrophage–tumor cell interactions and the role of macrophages in the response to anticancer therapies under obese conditions.
A Phase I/II Trial of Nivolumab plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study ADVL1412
Authors: Davis Kara L. , Fox Elizabeth , Isikwei Emasenyie , Reid Joel M. , Liu Xiaowei , Minard Charles G. , Voss Stephan , Berg Stacey L. , Weigel Brenda J. , Mackall Crystal L. 
Published: October 2022

Abstract

Purpose:
In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

Patients and Methods:
ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 mg/kg nivolumab plus 3 mg/kg ipilimumab) in Ewing sarcoma and rhabdomyosarcoma. Tumor response was measured using RECIST v1.1. Pharmacokinetics and PD-L1 expression on archival tissues were assessed.

Results:
Fifty-five eligible patients enrolled. Based on safety, tolerability, and similar drug exposure to the same doses administered in adults, DL2 was defined as the pediatric RP2D. Among 41 patients treated at the RP2D, 2 patients experienced dose-limiting toxicities during cycle 1, and 4 patients experienced toxicities beyond that period. Two patients had clinically significant sustained partial responses (1 rhabdomyosarcoma, 1 Ewing sarcoma) and 4 had stable disease. Among 8 patients treated at DL3, 3 dose-limiting toxicities (DLT) occurred, all immune-related adverse events; no objective responses were observed.

Conclusions:
The RP2D of nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) is well tolerated in children and young adults with solid tumors and shows some clinical activity. Increased dose of ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) was associated with increased toxicity without clinical benefit.
A (Controlled) Spill of IL2 for Localized Treatment of Mesothelioma
Authors: Palanki Rohan , Swingle Kelsey L. , Mitchell Michael J. 
Published: October 2022

SummaryA microencapsulated, cell-based IL2 cytokine factory was recently developed, and the safety and efficacy of this platform in a mouse model of mesothelioma were demonstrated. This platform has the potential to overcome current challenges in the delivery of therapeutic cytokines for cancer immunotherapy.See related article by Nash et al., p. 5121
Computational Modeling of TP63–TP53 Interaction and Rational Design of Inhibitors: Implications for Therapeutics
Authors: Ozdemir E. Sila , Gomes Michelle M. , Fischer Jared M. 
Published: October 2022

Abstract
Tumor protein p63 (TP63) is a member of the TP53 protein family that are important for development and in tumor suppression. Unlike TP53, TP63 is rarely mutated in cancer, but instead different TP63 isoforms regulate its activity. TA isoforms (TAp63) act as tumor suppressors, whereas ΔN isoforms are strong drivers of squamous or squamous-like cancers. Many of these tumors become addicted to ΔN isoforms and removal of ΔN isoforms result in cancer cell death. Furthermore, some TP53 conformational mutants (TP53CM) gain the ability to interact with TAp63 isoforms and inhibit their antitumorigenic function, while indirectly promoting tumorigenic function of ΔN isoforms, but the exact mechanism of TP63–TP53CM interaction is unclear. The changes in the balance of TP63 isoform activity are crucial to understanding the transition between normal and tumor cells. Here, we modeled TP63–TP53CM complex using computational approaches. We then used our models to design peptides to disrupt the TP63–TP53CM interaction and restore antitumorigenic TAp63 function. In addition, we studied ΔN isoform oligomerization and designed peptides to inhibit its oligomerization and reduce their tumorigenic activity. We show that some of our peptides promoted cell death in a TP63 highly expressed cancer cell line, but not in a TP63 lowly expressed cancer cell line. Furthermore, we performed kinetic–binding assays to validate binding of our peptides to their targets. Our computational and experimental analyses present a detailed model for the TP63–TP53CM interaction and provide a framework for potential therapeutic peptides for the elimination of TP53CM cancer cells.
Inhibition of NF-κB DNA Binding Suppresses Myeloma Growth via Intracellular Redox and Tumor Microenvironment Modulation
Authors: Bariana Manpreet , Cassella Elena , Rateshwar Janice , Ouk Samedy , Liou Hsiou-Chi , Heller Claudia , Colorado Iriana , Feinman Rena , Makhdoom Ali , Siegel David S. , Heller Glenn , Tuckett Andrea , Mondello Patrizia , Zakrzewski Johannes L. 
Published: October 2022

Abstract
Multiple myeloma is a plasma cell malignancy that is still largely incurable, despite considerable progress in recent years. NF-κB is a well-established therapeutic target in multiple myeloma, but none of the currently available treatment options offer direct, specific pharmacologic targeting of NF-κB transcriptional activity. Thus, we designed a novel direct NF-κB inhibitor (IT848) as a drug candidate with strong potential for clinical translation and conducted comprehensive in vitro and in vivo mechanistic studies in multiple myeloma cell lines, primary multiple myeloma cells, xenograft models, and immunocompetent mouse models of multiple myeloma. Here, we show that IT848 inhibits NF-κB activity through inhibition of DNA binding of all five NF-κB subunits. IT848 treatment of multiple myeloma cell lines and patient samples inhibited proliferation and induced caspase-dependent and independent apoptosis. In addition to direct NF-κB inhibitory effects, IT848 treatment altered the redox homeostasis of multiple myeloma cells through depletion of the reduced glutathione pool, selectively inducing oxidative stress in multiple myeloma but not in healthy cells. Multiple myeloma xenograft studies confirmed the efficacy of IT848 as single agent and in combination with bortezomib. Furthermore, IT848 significantly improved survival when combined with programmed death protein 1 inhibition, and correlative immune studies revealed that this clinical benefit was associated with suppression of regulatory T-cell infiltration of the bone marrow microenvironment. In conclusion, IT848 is a potent direct NF-κB inhibitor and inducer of oxidative stress specifically in tumor cells, displaying significant activity against multiple myeloma cells in vitro and in vivo, both as monotherapy as well as in combination with bortezomib or immune checkpoint blockade.