bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of experimental breast cancer using interleukin-12 gene therapy combined with anti–vascular endothelial growth factor receptor-2 antibody
Authors: Rakhmilevich Alexander L. , Hooper Andrea T. , Hicklin Daniel J. , Sondel Paul M. 
Published: June 2022

Abstract
We have shown previously that interleukin-12 (IL-12) gene therapy induced strong antitumor effects in several syngeneic murine tumor models including 4T1 mammary adenocarcinoma. Antiangiogenic treatment with a monoclonal antibody (mAb) directed against the vascular endothelial growth factor receptor-2 (VEGFR-2) is another promising treatment approach that can cause transient suppression of tumor growth. We hypothesized that the combination of IL-12 gene therapy and anti-VEGFR-2 mAb will achieve better antitumor and antimetastatic effects against 4T1 adenocarcinoma than each treatment alone via implementation of different mechanisms. Administration of anti-VEGFR-2 mAb into BALB/c mice bearing s.c. 4T1 tumors induced significant suppression of tumor growth, as did intratumoral administration of naked IL-12 DNA. The combined treatment with anti-VEGFR-2 mAb and IL-12 DNA resulted in significantly enhanced inhibition of tumor growth as compared with each treatment alone. This combination was also effective against spontaneous lung metastases. In T-cell–deficient nude mice, both IL-12 DNA and anti-VEGFR-2 mAb were effective in suppressing tumor growth. In T-cell- and natural killer cell–deficient scid/beige mice, only anti-VEGFR-2 mAb was effective, suggesting that natural killer cells are involved in the antitumor effects induced by IL-12 DNA. In both types of immunodeficient mice, the combination of anti-VEGFR-2 mAb and IL-12 DNA was as effective in suppressing 4T1 tumor growth as anti-VEGFR-2 mAb alone. Antitumor effects of anti-VEGFR-2 mAb were associated with the inhibition of angiogenesis within the tumors, whereas the antiangiogenic effect of IL-12 gene therapy was not detected. Our results show a therapeutic benefit of combining IL-12 gene therapy and anti-VEGFR-2 mAb for cancer treatment.
Association of Genome-Wide Polygenic Risk Score for Body Mass Index With Cardiometabolic Health From Childhood Through Midlife
Authors: Shi Mengyao , Chen Wei , Sun Xiao , Bazzano Lydia A. , He Jiang , Razavi Alexander C. , Li Changwei , Qi Lu , Khera Amit V. , Kelly Tanika N. 
Published: June 2022

Background:
Genetic information may help to identify individuals in childhood who are at increased risk for cardiometabolic disease.

Methods:
We included 1201 BHS (Bogalusa Heart Study) participants (832 White participants and 369 Black participants) who were followed up to 42.3 years, starting at a mean age of 9.8 years. A validated genome-wide polygenic risk score (PRS) was tested for association with midlife body mass index (BMI), fasting plasma glucose, and systolic blood pressure using multiple linear regression models. Cox proportional hazards models tested associations of the PRS with incident obesity, diabetes, and hypertension. All analyses were conducted according to race and adjusted for baseline age, sex, ancestry, and BMI.

Results:

The constructed PRS was significantly and modestly correlated with midlife BMI in both White and Black participants, with correlation coefficients of 0.27 (
P
=1.94×10
−8
) and 0.16 (
P
=5.50×10
−3
), respectively. In White participants, per SD increase of PRS was associated with an average 1.29 kg/m
2
higher BMI (
P
=4.44×10
−9
), 2.82 mg/dL higher fasting plasma glucose (
P
=1.17×10
−3
), and 1.09 mm Hg higher systolic blood pressure (
P
=3.57×10
−2
) at midlife. The PRS also conferred a 26% higher increased risk of obesity (
P
=3.50×10
−6
) in White participants. In addition, the variance in midlife BMI explained increased from 0.1973 to 0.2293 when PRS was added to the model including age, sex, principal components, and baseline BMI (
P
<0.0001). No associations were observed in Black participants.

Conclusions:
Adiposity-related genetic information independently predicted cardiometabolic health in White BHS participants. Null associations observed in Black BHS participants highlight the urgent need for PRS development in multi-ancestry populations.
Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring
Authors: Tong Wen , Allison Beth J. , Brain Kirsty L. , Patey Olga V. , Niu Youguo , Botting Kimberley J. , Ford Sage G. , Garrud Tessa A. , Wooding Peter F.B. , Shaw Caroline J. , Lyu Qiang , Zhang Lin , Ma Jin , Cindrova-Davies Tereza , Yung Hong Wa , Burton Graham J. , Giussani Dino A. 
Published: June 2022

Background:
Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology.

Methods:
We adopted an integrative approach to investigate the inter-relationship between chronic hypoxia during pregnancy with maternal, placental, and fetal outcomes, common in preeclampsia. We exploited a novel technique using isobaric hypoxic chambers and in vivo continuous cardiovascular recording technology for measurement of blood pressure in sheep and studied the placental stress in response to hypoxia at cellular and subcellular levels.

Results:
Chronic hypoxia in ovine pregnancy promoted fetal growth restriction (FGR) with evidence of fetal brain-sparing, increased placental hypoxia-mediated oxidative damage, and activated placental stress response pathways. These changes were linked with dilation of the placental endoplasmic reticulum (ER) cisternae and increased placental expression of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), combined with a shift towards an angiogenic imbalance in the maternal circulation. Chronic hypoxia further led to an increase in uteroplacental vascular resistance and the fall in maternal blood pressure with advancing gestation measured in normoxic pregnancy did not occur in hypoxic pregnancy.

Conclusions:
Therefore, we show in an ovine model of sea-level adverse pregnancy that chronic hypoxia recapitulates physiological and molecular features of preeclampsia in the mother, placenta, and offspring.
Association Between Hypertension and Incident Infective Endocarditis
Authors: Lee Gyu Bae , Shin Koh Eun , Han Kyungdo , Son Ho-Sung , Jung Jae-Seung , Kim Yang-Hyun , Kim Hee-Jung 
Published: June 2022

Background:
This study aimed to evaluate the association of hypertension with incident infective endocarditis (IE) by investigating the incidence of IE according to blood pressure levels using the National Health Insurance Service database.

Methods:
The data of 4 080 331 individuals linked to the health screening database in 2009 were retrieved (males, 55.08%; mean age, 47.12±14.13 years). From 2009 to 2018, the risk factors for the first episode of IE were investigated. Hypertension was categorized into normotension, prehypertension, hypertension, and hypertension with medication. The Cox proportional hazard model assessed the effect of blood pressure level during the health screening exam on incident IE.

Results:

During the 9-year follow-up, 812 (0.02%) participants were diagnosed with IE. The incidence rates of IE in the normotension, prehypertension, hypertension, and hypertension with medication groups were 0.9, 1.4, 2.6, and 6.0 per 100 000 person-years, respectively. Those with prehypertension, hypertension, and hypertension with medication were correlated with an increased risk of IE in a dose-response manner compared with the normotension group (hazard ratio, 1.33 [95% CI, 1.06–1.68]; hazard ratio, 1.98 [1.48–2.66]; hazard ratio, 2.56 [2.02–3.24], respectively, all
P
<0.001).

Conclusions:
In a large national cohort study with an average follow-up of 9 years, increased blood pressure was identified as a risk factor for incident IE in a dose-dependent manner. Hypertension increases the public health care burden by acting as a risk factor for rare infective heart diseases.
Structure and Dynamics of Islamic Social Formations (Seventh–Fourteenth Century)
Authors: Batou Jean 
Published: June 2022

Abstract
From the seventh to the fourteenth century, the Muslim world’s key actors were free peasants working limited and scattered cultivated areas, whose communities paid heavy taxes. A distinct nomadic mode of production dominated the arid lands and their warlike pastoral tribes. Wealthy merchants and artisans controlled urban ideological production, living next to actual ruling classes, who drew exceptional material privileges from their proximity to the state. Since the latter’s status contradicted the contractual community’s values, political power was socially alienated and needed support from paid soldiers and often co-opted religious notables. The author describes Islamic social formations as real flesh-and-blood beings who developed original features on the same tributary mode of production’s skeleton. He shows that comparable dialectical oppositions enlivened them, stemming from uneven and combined development processes. Thus, their states and villages, barren lands and city markets, contractual ideology and monarchical powers were permanently in conflictual interaction.
Prepregnancy and Gestational Diabetes and Cessation of Breastfeeding <1 Week Postpartum, United States, 2016-2018
Authors: Kortsmit Katherine , Boone Kirsten I. , Warner Lee , Horan Jessica , Bower Julie K. , Gallo Maria F. 
Published: June 2022

Objectives: Diabetes may delay milk letdown, and perceiving milk production as insufficient can lead to breastfeeding cessation. We evaluated whether prepregnancy or gestational diabetes is associated with cessation of breastfeeding by 1 week postpartum. Methods: We analyzed 2016-2018 data from 42 sites in the Pregnancy Risk Assessment Monitoring System, a population-based survey of women with a recent live birth. Participants were surveyed 2-6 months after childbirth. We used logistic regression models to evaluate the relationship between prepregnancy or gestational diabetes only and breastfeeding <1 week postpartum among women who had initiated breastfeeding. Results: Among 82 050 women who initiated breastfeeding, 4.5% reported breastfeeding <1 week postpartum. Overall, 11.7% of women reported any history of diabetes in the 3 months before becoming pregnant; 3.3% reported prepregnancy diabetes, and 8.4% reported gestational diabetes only. In both unadjusted and adjusted models, the prevalence of breastfeeding <1 week postpartum did not differ significantly among women with prepregnancy diabetes or gestational diabetes only compared with women without any history of diabetes. The prevalence of breastfeeding <1 week postpartum was 4.4% among women without any history of diabetes, 5.6% among women with prepregnancy diabetes (adjusted prevalence ratio [aPR] = 1.15; 95% CI, 0.91-1.46), and 4.5% among women with gestational diabetes only (aPR = 1.01; 95% CI, 0.84-1.20). Conclusions: We found no association between a history of diabetes prepregnancy or gestational diabetes only and breastfeeding <1 week postpartum in a large, population-based survey of postpartum women who initiated breastfeeding. Regardless of their diabetes status, women who want to breastfeed might benefit from interventions that support their ability to continue breastfeeding.
Oral health and knowledge of sighted children and children with visual impairment and their parents’ role in it: A comparative study
Authors: Cunha Soraia Ramos , Fátima Bizarra Maria de 
Published: June 2022

Aim: The present study aims to evaluate oral health knowledge and habits of children with visual impairment by comparison with their sighted counterparts and also evaluates parental knowledge and involvement in children’s oral hygiene routines. Methods: This observational and transversal study included the participation of 68 children (34 were visually impaired and 34 were sighted), from seven schools from Lisbon. The participants with visual impairment were age and gender-matched with their sighted counterparts to minimize variations in the analysis. In all, 52.9% of children were male, with average age of 11.15 (±3.413) years [6; 18]. The children and parents completed one survey each. Children were submitted to an oral examination to evaluate oral health. Results: Participants with visual impairment showed a non-significant increase in the decayed, missing, and filled teeth index (dmft), gingival, and oral hygiene indexes. Both groups’ gingival state was mostly classified as excellent, and oral hygiene was mainly classified as excellent/good. More children with visual impairment (85.7%) needed help with teeth brushing ( p = .046) and were more likely to miss dentist check-ups more often ( p = .025). Also, sighted children and their parents demonstrated more knowledge about oral health. Conclusion: Children with visual impairment and their parents showed less favorable results, justifying the need to promote oral health education to this demographic.
Cultural adaptation of the Italian version of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Event (PRO-CTCAE®)
Authors: Caminiti Caterina , Bryce Jane , Riva Silvia , Ng Diane , Diodati Francesca , Iezzi Elisa , Sparavigna Lucia , Novello Silvia , Porta Camillo , Del Mastro Lucia , Procopio Giuseppe , Cinieri Saverio , Falzetta Amalia , Calabrò Fabio , Lorusso Vito , Cogoni Alessio Aligi , Tortora Giampaolo , Maruzzo Marco , Passalacqua Rodolfo , Cognetti Francesco , Adamo Vincenzo , Capelletto Enrica , Ferrari Alessandra , Bagnalasta Michela , Bassi Maurizio , Nicelli Annalisa , De Persis Davide , D’Acunti Alessia , Iannelli (patient) Elisabetta , Perrone Francesco , Mitchell Sandra A. 
Published: June 2022

Introduction: US National Cancer Institute’s (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. Methods: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). Results: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). Discussion: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.
Design and synthesis of high-performance poly(amide-imide) for multifunctional electromagnetic interference shielding films
Authors: Zhuang Changlong , Wang Yanbin , Chang Chengbi , Fan Zicheng , Hou Shuhan , Zhou Chen , Dong Hao , Xia Leier , Luo Zhonglin , Wang Biaobing 
Published: June 2022

The exploration of flexible, transparent, anti-corrosion and thermally stable electromagnetic interference (EMI) shielding materials is still a huge challenge and urgently demanded in the civil and military fields. Herein, two novel high-performance poly (amide-imide)s (PAIs) were designed and used to fabricate sandwich structure EMI shielding films through simple layer-by-layer casting method. Combining advantages of PAI and silver nanowires (Ag NWs), PAI/Ag NWs composite films showed a shielding effectiveness (SE) of 35 dB and simultaneously possessed an optical transmittance of beyond 80%. More encouragingly, the composite films remained more than 92% EMI SE with random deformations (>5000 times). Furthermore, benefitting from the excellent properties of PAI matrix and sandwich structure of EMI shielding films, the EMI SE was almost unchanged even when they were exposed to air for 30 min at 160°C. On the other hand, the PAI/Ag NWs composite films still exhibited EMI SE of more than 30 dB when they were dipped into aqueous solution for 1 h by varying pH values from 2 to 13. These results demonstrated that PAI and Ag NWs was a good combination to prepare EMI shielding materials with excellent comprehensive performances.
The evolving moral economy of indebtedness in Chile: resignifying credit and debt in the oldest neoliberal society
Authors: Marambio-Tapia Alejandro 
Published: June 2022

Credit is ubiquitous in the life of Chilean households, the oldest neoliberal society. It is a key feature in the budgeting, shopping, and consuming practices of families. Consequently, to be indebted is a normal expectation in Chile. Families engage with the ‘necessary evil’ of credit in different ways, representing a massive, regular use of credit as short, medium and long-term leverage tools, with store cards being the main source of credit for lower and moderate income families in general. Moral obligations together with conventional and unconventional financial knowledge accompany the everyday situated economic practices of families. Addressing both the normalisation and the moralisation of credit, I attempt to make the case for the ongoing resignification of credit and debt and the evolving moral assessments of indebtedness, focusing on moderate and low-income households, namely those who embrace credit during recent decades. This article contributes to the discussion about the meaning of debt, to understand the financialisation of everyday life by looking at situated economic practices, and to recognise the social, moral and relational foundations of the economic practices. From the coming of the expansion of credit, households have learnt to deal with economic rationalities and internal and external moral judgements in order to justify their use of credit. Together with structural factors, this develops indebtedness assessments from detachment to naturalisation, placing credit and debt in the centre of ‘decent life’ expectations.
Development and use of a checklist for the implementation of medication for opioid use disorder in jails
Authors: Ludwig Ariel , Monico Laura B. , Blue Thomas , Gordon Michael S. , Schwartz Robert P. , Mitchell Shannon Gwin 
Published: June 2022

Background: In light of short lengths of stay and proximity to communities of release, jails are well-positioned to intervene in opioid use disorder (OUD). However, a number of barriers have resulted in a slow and limited implementation. Methods: This paper describes the development and testing of a Medication for Opioid Use Disorder (MOUD) Implementation Checklist developed as part of a Building Bridges project, a two-year planning grant which supported 16 US jail systems as they prepared to implement or expand MOUD services. Results: Although initially developed to track changes within sites participating in the initiative, participants noted its utility for identifying evidence-based benchmarks through which the successful implementation of MOUDs could be tracked by correctional administrators. Conclusions: The findings suggest that this checklist can both help guide and illustrate progress toward vital changes facilitated through established processes and supports. Plain Language Summary: People incarcerated in jails are more likely to have opioid use disorder than the general population. Despite this, jails in the United States (U.S.) often offer limited or no access to Medication for Opioid Use Disorder (MOUD). The Building Bridges project was designed to address this gap in 16 U.S. jail systems as they prepared to implement or expand MOUD services. This article addresses the use of a MOUD checklist that was initially designed to help the jails track changes toward evidence-based benchmarks. The findings suggest that this checklist can both help guide and illustrate progress toward vital changes facilitated through established processes and supports.
Biologics in severe asthma: the role of real-world evidence from registries
Authors: Paoletti Giovanni , Pepys Jack , Casini Marta , Di Bona Danilo , Heffler Enrico , Goh Celine Y.Y. , Price David B. , Canonica Giorgio Walter 
Published: June 2022

Asthma is one of the most common noncommunicable diseases; in the majority of patients it is well controlled with inhaled bronchodilators and inhaled corticosteroids, but the management of severe asthma has been a significant challenge historically. The introduction of novel biologic drugs in the past few decades has revolutionised the field, presenting physicians with a variety of biologic drugs with different mechanisms for the treatment of severe asthma.It is of crucial importance to evaluate the effectiveness of these drugs by following their “real-life” effectiveness rather than relying solely on their efficacy, established in carefully designed clinical trials, which therefore do not necessarily match the profile of the real-life patient. Understanding the actual effectiveness of the specific drugs in real-life patients is a crucial part of tailoring the right drugs to the right patients. Registries serve as an important tool in obtaining real-life evidence, since they are in effect observational studies, following the entire patient population.
Sfcnn: a novel scoring function based on 3D convolutional neural network for accurate and stable protein–ligand affinity prediction
Authors: Wang Yu , Wei Zhengxiao , Xi Lei 
Published: June 2022

AbstractBackgroundComputer-aided drug design provides an effective method of identifying lead compounds. However, success rates are significantly bottlenecked by the lack of accurate and reliable scoring functions needed to evaluate binding affinities of protein–ligand complexes. Therefore, many scoring functions based on machine learning or deep learning have been developed to improve prediction accuracies in recent years. In this work, we proposed a novel featurization method, generating a new scoring function model based on 3D convolutional neural network.ResultsThis work showed the results from testing four architectures and three featurization methods, and outlined the development of a novel deep 3D convolutional neural network scoring function model. This model simplified feature engineering, and in combination with Grad-CAM made the intermediate layers of the neural network more interpretable. This model was evaluated and compared with other scoring functions on multiple independent datasets. The Pearson correlation coefficients between the predicted binding affinities by our model and the experimental data achieved 0.7928, 0.7946, 0.6758, and 0.6474 on CASF-2016 dataset, CASF-2013 dataset, CSAR_HiQ_NRC_set, and Astex_diverse_set, respectively. Overall, our model performed accurately and stably enough in the scoring power to predict the binding affinity of a protein–ligand complex.ConclusionsThese results indicate our model is an excellent scoring function, and performs well in scoring power for accurately and stably predicting the protein–ligand affinity. Our model will contribute towards improving the success rate of virtual screening, thus will accelerate the development of potential drugs or novel biologically active lead compounds.