bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of switching from a metered dose inhaler to a dry powder inhaler on climate emissions and asthma control: post-hoc analysis
Authors: Woodcock Ashley , Janson Christer , Rees Jamie , Frith Lucy , Löfdahl Magnus , Moore Alison , Hedberg Martin , Leather David 
Published: February 2022

ObjectiveTo compare the effects of switching from a pressurised metered dose inhaler (pMDI)-based to a dry powder inhaler (DPI)-based maintenance therapy versus continued usual care on greenhouse gas emissions (carbon dioxide equivalents, CO2e) and asthma control.MethodsThis post-hoc analysis was based on a subset of 2236 (53%) patients from the Salford Lung Study in Asthma who at baseline were using a pMDI-based controller therapy. During the study patients were randomised to fluticasone furoate/vilanterol (FF/VI) via the ELLIPTA DPI (switched from pMDI to DPI) (n=1081) or continued their usual care treatment (n=1155), and were managed in conditions close to everyday clinical practice. Annual CO2e (kg) was calculated for the total number of maintenance and rescue inhalers prescribed. Asthma control was assessed by the proportion of ACT responders (composite of ACT total score ≥20 and/or increase from baseline ≥3).ResultsThe groups were well matched for demographic characteristics and baseline Asthma Control Test (ACT) total score (mean age: 49 years; mean ACT score: usual care, 16.6; FF/VI, 16.5). Annual CO2e kg per patient (maintenance plus rescue therapy) was significantly lower with FF/VI DPI treatment (‘switch’ group) than usual care (least squares geometric mean 108 kg (95% CI 102 to 114) vs 240 kg (95% CI 229 to 252), p<0.001). Asthma control was consistently superior over the 12 months in the FF/VI DPI group compared with usual care.ConclusionsPatients switching from a pMDI-based to a DPI-based maintenance therapy more than halved their inhaler carbon footprint without loss of asthma control. The remaining inhaler carbon footprint could be reduced through switches from pMDI to DPI rescue medications or alternative lower-carbon footprint rescue inhalers if available. Asthma control improved in both groups, with greater control demonstrated in those initiated on FF/VI DPI.Trial registration numberNCT01706198.
Pediatric dog bite injuries in the USA: a systematic review
Authors: Patterson Kelli Nicole , Horvath Kyle Z , Minneci Peter C , Thakkar Rajan , Wurster LeeAnn , Noffsinger Dana L , Bourgeois Tran , Deans Katherine J 
Published: February 2022

IntroductionDog bites are one of the leading causes of non-fatal emergency room visits in children. These injuries not only cause physical harm but can lead to long-term psychological stress. This study evaluated the current literature related to pediatric dog bite injuries to identify research gaps which should be prioritized to improve a major public health concern.MethodsWe performed a keyword search of PubMed, Scopus, and OVID Medline databases (January 1980– March 2020) for all published studies focused on dog bite injuries in the pediatric population (≤18 years of age) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.ResultsOut of 1859 abstracts screened, 43 studies involving 86 880 patients were included. Twenty-nine studies were retrospective chart reviews characterizing the epidemiology of dog bites and their associated treatment outcomes; six were prospective cohort studies; two were cross-sectional studies; and six were experimental studies. Synthesized results demonstrate that children <9 years of age suffer the greatest burden of injuries, with children <6 years of age at higher risk of more severe injuries involving the head, neck, and face.ConclusionStudies analyzing the prevention or psychosocial consequences of dog bites injuries are needed.
Needs assessment of parents for a patient decision aid in pediatric interval appendectomy via the qualitative interview method
Authors: Grandpierre Viviane , Duba Katherine , Toupin April Karine , Oltean Irina , Weir Arielle , Nasr Ahmed 
Published: February 2022

ObjectivesAppendicitis is one of the most commonly encountered pediatric surgical diagnoses, with non-operative management of perforated appendicitis leading to two treatment options: an interval appendectomy (IA) or expectant management. The primary objective of this study was to assess parents’ need for a patient decision aid (PDA) among parents considering IA or expectant management. A secondary objective was to determine parent preferences for the format and distribution plan of a drafted patient decision aid.MethodsCoulter’s systematic development process for PDA was used to guide the assessment interviews for parents. Participants included caregivers of a patient who experienced perforated appendicitis, and admission between 2019 and 2020. Semi-structured individual interviews were conducted to collect information about decision-making needs of parents of children who experienced perforated appendicitis.ResultsA total of 12 different parents participated in the interviews. Results indicate decisional conflict associated with the lack of evidence for optimal treatment, supporting the need for the development of a patient decision aid to assist in clarifying information and parent values with practitioners. Parents clearly identified a need for evidence to support decision-making in various formats (eg, pamphlet or electronic). Timing of when to deliver the PDA varied (ie, during hospital admission, at discharge, or at follow-up appointment).ConclusionResults indicated various factors contributing to parental decisional conflict, including the lack of evidence showing the optimal treatment, the need for more information, and guidance from practitioners. Overall, findings indicate a strong need for a patient decision aid.
The imaginary potential and entropic force of heavy quarkonia in strongly coupled $$ {\mathcal {N}}=4 $$ supersymmetric Yang–Mills plasma on the Coulomb branch
Authors: Kioumarsipour M. , Sadeghi J. 
Published: February 2022

AbstractThere are two important different mechanisms, the imaginary potential and entropic force, to investigate the dissociation of heavy quarkonia. In this paper, we calculate these two quantities for static and moving quarkonia in the rotating black 3-brane Type IIB supergravity solution dual to $$ {\mathcal {N}}=4 $$

N
=
4

super Yang–Mills theory on the Coulomb branch (cSYM) at strong coupling. At $$ T\ne 0 $$

T
≠
0

, there are two black hole branches: the large and small black hole branches. We investigate the effects of rotating parameter and rapidity for the static and moving quakonium at the large and small black hole branches. We find both mechanisms have the same results. In the large black hole branch: as $$ T/\Lambda $$

T
/
Λ

and $$ \beta $$
β
increase the thermal width decreases and so the suppression becomes stronger. In the small black hole branch: increasing $$ T/\Lambda $$

T
/
Λ

leads to increasing the thermal width and the quarkonium dissociates harder but $$ \beta $$
β
has an opposite effect.
Efficient-Grad:

Efficient

Training Deep Convolutional Neural Networks on Edge Devices with

Grad

ient Optimizations
Authors: Hong Ziyang , Yue C. Patrick 
Published: February 2022

With the prospering of mobile devices, the distributed learning approach, enabling model training with decentralized data, has attracted great interest from researchers. However, the lack of training capability for edge devices significantly limits the energy efficiency of distributed learning in real life. This article describes Efficient-Grad, an algorithm-hardware co-design approach for training deep convolutional neural networks, which improves both throughput and energy saving during model training, with negligible validation accuracy loss.
The key to Efficient-Grad is its exploitation of two observations. Firstly, the sparsity has potential for not only activation and weight, but gradients and the asymmetry residing in the gradients for the conventional back propagation (BP). Secondly, a dedicated hardware architecture for sparsity utilization and efficient data movement can be optimized to support the Efficient-Grad algorithm in a scalable manner. To the best of our knowledge, Efficient-Grad is the first approach that successfully adopts a feedback-alignment (FA)-based gradient optimization scheme for deep convolutional neural network training, which leads to its superiority in terms of energy efficiency. We present case studies to demonstrate that the Efficient-Grad design outperforms the prior arts by 3.72x in terms of energy efficiency.
Effects of Dietary Phospholipid and Cholesterol Levels on Growth, Molting Performance, and Ovary Development in Female Juvenile Crayfish (Procambarus clarkii)
Authors: Hou Shouquan , Zhu Shaicheng , Li Jinghao , Huang Jin , Li Jiayao , Cheng Yongxu 
Published: February 2022

The interaction between phospholipid (PL) and cholesterol (CH) on growth performance, molting rate, hepatopancreas fatty acid composition, and ovary development of the female red swamp crayfish (Procambarus clarkii) was investigated. Nine diets containing three PL levels (0, 20, and 60 g/kg) and three CH levels (0, 5, and 10 g/kg) were included in the study. Female crayfish (initial weight:

5.92
±
0.03

g) were reared for 60 days. There was no significant interaction between dietary PL and CH levels (

P
>
0.05

). However, the best growth performance and ovarian development were observed in crayfish receiving the 60 g/kg PL and 10 g/kg CH diet. High PL levels promoted CH transport in the hepatopancreas, and long-chain unsaturated fatty acid (C20:4n-6, C20:5n-3, and C22:6n-3) content of the hepatopancreas increased with the addition of PL in the diet. The molting rate increased with increasing CH levels in the diet containing 60 g/kg PL. Real-time quantitative polymerase chain reaction revealed that dietary CH enhanced the molting rate by improving the ecdysone receptor genes at transcription. This study showed that crayfish fed a diet containing 10 g/kg CH and 60 g/kg PL obtained maximum growth, molting rate, and ovary development.
First Report of the HEV Seroprevalence and the Risk Factor Assessment in the West Bank, Palestine, during the Period of 2015–2017
Authors: Dumaidi Kamal , Abudamous Alaa M. , Abu-Helu Rasmi , Al-Jawabreh Hanan , Dumaidi Yazan , Al-Jawabreh Amer 
Published: February 2022

Hepatitis E virus is emerging viral hepatitis with hyperendemicity in many countries. Data on the burden of disease is not available in Palestine. This study aims to determine the seroprevalence and the risk factors of the HEV among the general population of the West Bank, Palestine. In this cross-sectional study, a total of 432 sera samples from 40 localities in the eleven districts of the West Bank and Jerusalem, Palestine, during the period of March 2015 to March 2017, were tested for HEV-IgG. A structured questionnaire was used to collect data of the participants’ demographics and disease risk factors. The overall seroprevalence was 3.7%. Level of education was significantly inversely associated with HEV seropositivity (

P
=
0.04

). Purely spatial analysis did not detect any significant cluster related to the distribution of HEV-IgG cases; however, living in the southern West Bank is shown to be significantly associated with HEV. Age was also associated with HEV seropositivity. The young (<19 years) and adults (>40 years) had the highest prevalence, compared to those between 20 to 39 years old (

P
=
0.12

). Furthermore, males and those in contact with animals were associated with HEV seropositivity (

P
=
0.1
and
0.3

, respectively). In conclusion, the seroprevalence of HEV IgG in the West Bank, Palestine is low. Several well-investigated risk factors cannot be supported by our results due to the small number of the positive HEV-IgG samples. Finally, this study is useful for providing a first look into the seroepidemiology of HEV in Palestine.
Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer
Authors: Hong Wan Xing , Sagiv-Barfi Idit , Czerwinski Debra K. , Sallets Adrienne , Levy Ronald 
Published: February 2022

Abstract

The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into the tumor microenvironment, eradicating simultaneous untreated sites of metastatic disease. Here we explore the application of this in situ immunotherapy to the neoadjuvant setting. Current neoadjuvant checkpoint blockade therapy is delivered systemically, resulting in off-target adverse effects. In contrast, intratumoral immunotherapy minimizes the potential for toxicities and allows for greater development of combination therapies. In two metastatic solid tumor models, neoadjuvant intratumoral immunotherapy generated a local T-cell antitumor response that then acted systemically to attack cancer throughout the body. In addition, the importance of timing between neoadjuvant immunotherapy and surgical resection was established, as well as the increased therapeutic power of adding systemic anti-PD1 antibody. The combination of local and systemic immunotherapy generated an additional survival benefit due to synergistic inhibitory effect on tumor-associated macrophages. These results provide a strong rationale for translating this neoadjuvant intratumoral immunotherapy to the clinical setting, especially in conjunction with established checkpoint inhibitors.

Significance:
This work demonstrates the ability of neoadjuvant intratumoral immunotherapy to target local and distant metastatic disease and consequently improve survival.
Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility
Authors: Testori Alessandro , Vaksman Zalman , Diskin Sharon J. , Hakonarson Hakon , Capasso Mario , Iolascon Achille , Maris John M. , Devoto Marcella 
Published: February 2022

Abstract

Background:
Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease.

Methods:
We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs.

Results:
We confirmed the known neuroblastoma susceptibility gene BARD1 at genome-wide significance in the subset of high-risk cases. We also estimated local admixture across the autosomal genome in the AA cases and controls and detected a signal at 4q31.22 where cases show an increase in European ancestry. A region at 17p13.1 showed increased African ancestry in the subgroup of high-risk cases with respect to intermediate- and low-risk cases. Using results from our published European American (EA) genome-wide association study (GWAS), we found that a polygenic score that included all independent SNPs showed a highly significant association (P value = 1.8 × 10−73) and explained 19% of disease risk variance in an independent EA cohort. In contrast, the best fit polygenic score (P value = 3.2 × 10−11) in AAs included only 22 independent SNPs with association P value &lt; 2.75 × 10−6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs.

Conclusions:
These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion.

Impact:
This work supports the need for GWAS to be performed in populations of all races and ethnicities.
A Predictive Model of Noncardia Gastric Adenocarcinoma Risk Using Antibody Response toHelicobacter pyloriProteins and Pepsinogen
Authors: Murphy John D. , Olshan Andrew F. , Lin Feng-Chang , Troester Melissa A. , Nichols Hazel B. , Butt Julia , Qiao You-Lin , Abnet Christian C. , Inoue Manami , Tsugane Shoichiro , Epplein Meira 
Published: February 2022

AbstractBackground:Blood-based biomarkers for gastric cancer risk stratification could facilitate targeting screening to people who will benefit from it most. The ABC Method, which stratifies individuals by their Helicobacter pylori infection and serum-diagnosed chronic atrophic gastritis status, is currently used in Japan for this purpose. Most gastric cancers are caused by chronic H. pylori infection, but few studies have explored the capability of antibody response to H. pylori proteins to predict gastric cancer risk in addition to established predictors.Methods:We used the least absolute shrinkage and selection operator (Lasso) to build a predictive model of noncardia gastric adenocarcinoma risk from serum data on pepsinogen and antibody response to 13 H. pylori antigens as well as demographic and lifestyle factors from a large international study in East Asia.Results:Our best model had a significantly (P &lt; 0.001) higher AUC of 73.79% [95% confidence interval (CI), 70.86%–76.73%] than the ABC Method (68.75%; 95% CI, 65.91%–71.58%). At 75% specificity, the new model had greater sensitivity than the ABC Method (58.67% vs. 52.68%) as well as NPV (68.24% vs. 66.29%).Conclusions:Along with serologically defined chronic atrophic gastritis, antibody response to the H. pylori proteins HP 0305, HP 1564, and UreA can improve the prediction of gastric cancer risk.Impact:The new risk stratification model could help target more invasive gastric screening resources to individuals at high risk.
DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer
Authors: Kurani Hetakshi , Razavipour Seyedeh Fatemeh , Harikumar Kuzhuvelil B. , Dunworth Matthew , Ewald Andrew J. , Nasir Apsra , Pearson Gray , Van Booven Derek , Zhou Zhiqun , Azzam Diana , Wahlestedt Claes , Slingerland Joyce 
Published: February 2022

Abstract

Purpose:
Although chemotherapies kill most cancer cells, stem cell–enriched survivors seed metastasis, particularly in triple-negative breast cancers (TNBC). TNBCs arise from and are enriched for tumor stem cells. Here, we tested if inhibition of DOT1L, an epigenetic regulator of normal tissue stem/progenitor populations, would target TNBC stem cells.

Experimental Design:
Effects of DOT1L inhibition by EPZ-5676 on stem cell properties were tested in three TNBC lines and four patient-derived xenograft (PDX) models and in isolated cancer stem cell (CSC)-enriched ALDH1+ and ALDH1− populations. RNA sequencing compared DOT1L regulated pathways in ALDH1+ and ALDH1− cells. To test if EPZ-5676 decreases CSC in vivo, limiting dilution assays of EPZ-5676/vehicle pretreated ALDH1+ and ALDH1− cells were performed. Tumor latency, growth, and metastasis were evaluated. Antitumor activity was also tested in TNBC PDX and PDX-derived organoids.

Results:
ALDH1+ TNBC cells exhibit higher DOT1L and H3K79me2 than ALDH1−. DOT1L maintains MYC expression and self-renewal in ALDH1+ cells. Global profiling revealed that DOT1L governs oxidative phosphorylation, cMyc targets, DNA damage response, and WNT activation in ALDH1+ but not in ALDH1− cells. EPZ-5676 reduced tumorspheres and ALDH1+ cells in vitro and decreased tumor-initiating stem cells and metastasis in xenografts generated from ALDH1+ but not ALDH1− populations in vivo. EPZ-5676 significantly reduced growth in vivo of one of two TNBC PDX tested and decreased clonogenic 3D growth of two other PDX-derived organoid cultures.

Conclusions:
DOT1L emerges as a key CSC regulator in TNBC. Present data support further clinical investigation of DOT1L inhibitors to target stem cell–enriched TNBC.
FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy
Authors: Przepiorka Donna , Le Robert Q. , Ionan Alexei , Li Ruo-Jing , Wang Ying-Hong , Gudi Ramadevi , Mitra Soumya , Vallejo Jonathon , Okusanya Olanrewaju O. , Ma Lian , Yang Yuching , Patel Paresma , Mezaache Djelila , Shah Rakhi , Banerjee Anamitro , McLamore Sherita , Maung Adam N. , Goldberg Kirsten B. , Pazdur Richard , Theoret Marc R. , De Claro R. Angelo 
Published: February 2022

Abstract
On July 16, 2021, the FDA approved belumosudil, a kinase inhibitor, for adult and pediatric patients 12 years and older with chronic GvHD (cGvHD) after failure of at least two prior lines of systemic therapy. Approval was based on the results of Study KD025–213, which included 65 patients with cGvHD treated with belumosudil 200 mg daily in an open-label, single-arm cohort. Efficacy was determined by the overall response rate (ORR) through Cycle 7 Day 1, which included complete response (CR) or partial response (PR) according to the 2014 NIH consensus criteria, and durability of response. The ORR through Cycle 7 Day 1 was 75% [95% confidence interval (CI), 63–85]; 6% of patients achieved a CR, and 69% achieved a PR. The median duration of response was 1.9 months (95% CI, 1.2–2.9), and 62% (95% CI, 46–74) of responding patients remained alive without new systemic therapy for at least 12 months from response. The common adverse reactions were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma-glutamyl transferase increased, lymphocytes decreased, and hypertension. Additional study is warranted to confirm safety with long-term use.
Dual G9A/EZH2 Inhibition Stimulates Antitumor Immune Response in Ovarian High-Grade Serous Carcinoma
Authors: Spiliopoulou Pavlina , Spear Sarah , Mirza Hasan , Garner Ian , McGarry Lynn , Grundland-Freile Fabio , Cheng Zhao , Ennis Darren P. , Iyer Nayana , McNamara Sophie , Natoli Marina , Mason Susan , Blyth Karen , Adams Peter D. , Roxburgh Patricia , Fuchter Matthew J. , Brown Bob , McNeish Iain A. 
Published: February 2022

Abstract
Ovarian high-grade serous carcinoma (HGSC) prognosis correlates directly with presence of intratumoral lymphocytes. However, cancer immunotherapy has yet to achieve meaningful survival benefit in patients with HGSC. Epigenetic silencing of immunostimulatory genes is implicated in immune evasion in HGSC and re-expression of these genes could promote tumor immune clearance. We discovered that simultaneous inhibition of the histone methyltransferases G9A and EZH2 activates the CXCL10–CXCR3 axis and increases homing of intratumoral effector lymphocytes and natural killer cells while suppressing tumor-promoting FoxP3+ CD4 T cells. The dual G9A/EZH2 inhibitor HKMTI-1–005 induced chromatin changes that resulted in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family. Importantly, treatment with HKMTI-1–005 improved the survival of mice bearing Trp53−/− null ID8 ovarian tumors and resulted in tumor burden reduction. These results indicate that inhibiting G9A and EZH2 in ovarian cancer alters the immune microenvironment and reduces tumor growth and therefore positions dual inhibition of G9A/EZH2 as a strategy for clinical development.