bluuebunny/crossref_metadata_2025_split huggingface dataset:
There should always be a free lunch: the impact of COVID-19 lockdown suspension of the mid-day meal on nutriture of primary school children in Karnataka, India
Authors: Thankachan Prashanth , Selvam Sumithra , Narendra Agnita R , Mishra Hari N , Sachdev Harshpal S , Thomas Tinku , Kurpad Anura V 
Published: July 2022

BackgroundThe COVID-19 pandemic lockdown in 2020 resulted in school closures with eventual suspension of the mid-day meal programme, biannual deworming and iron–folic acid supplements. One year into the lockdown, we evaluated the impact of the withdrawal of these programmes on the nutritional status of rural primary-school children, aged 6–12 years, in Karnataka, India.MethodsAnthropometry, haemoglobin, serum ferritin and C reactive protein were measured in 290 children at two time points, 1 year apart, starting from just before the lockdown (February 2020 to February 2021).ResultsThe prevalence of anaemia doubled from 21% to 40% (p<0.0001) with more pronounced changes in older girls (10%–53%); however, the prevalence of iron deficiency did not change (48.8%–51.9%), despite cessation of deworming and iron/folic acid supplements.ConclusionThe increase in anaemia was due to limiting intakes of other erythropoietic nutrients, possibly due to a lower dietary diversity. The mid-day lunch meal at school (MDM) is an important part of daily food intake in rural school children, and it is important to maintain dietary diversity through the delivery of MDM for such vulnerable groups.
Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide: a protocol for a systematic review of observational studies
Authors: Carli Tanja , Locatelli Igor , Košnik Mitja , Kukec Andreja 
Published: July 2022

IntroductionSystemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide.Methods and analysisSearching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review.Ethics and disseminationNo ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals.PROSPERO registration numberCRD42021260922.
Acute pain pathways: protocol for a prospective cohort study
Authors: Jeffery Molly Moore , Ahadpour Mitra , Allen Summer , Araojo Richardae , Bellolio Fernanda , Chang Nancy , Ciaccio Laura , Emanuel Lindsay , Fillmore Jonathan , Gilbert Gregg H , Koussis Patricia , Lee Christine , Lipkind Heather , Mallama Celeste , Meyer Tamra , Moncur Megan , Nuckols Teryl , Pacanowski Michael A , Page David B , Papadopoulos Elektra , Ritchie Jessica D , Ross Joseph S , Shah Nilay D , Soukup Mat , St. Clair Christopher O , Tamang Stephen , Torbati Sam , Wallace Douglas W , Zhao Yueqin , Heckmann Rebekah 
Published: July 2022

IntroductionOpioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses.Methods and analysisThis multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients’ patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids.Ethics and disseminationThis study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public.Trial registration numberNCT04509115.
Knowledge, attitude and practice of community pharmacy personnel in tuberculosis patient detection: a multicentre cross-sectional study in a high-burden tuberculosis setting
Authors: Pradipta Ivan Surya , Khairunnisa Khairunnisa , Bahar Muh Akbar , Kausar Mersa Nurain , Fitriana Efi , Ruslami Rovina , Aarnoutse Rob E , Abdulah Rizky 
Published: July 2022

IntroductionControl of tuberculosis (TB) is hampered by suboptimal case detection and subsequent delays in treatment, which is worsened by the COVID-19 pandemic. The community pharmacy is reported as the place for first aid medication among patients with TB. We, therefore, analysed knowledge, attitude and practice (KAP) on TB patient detection (TBPD) of community pharmacy personnel, aiming to find innovative strategies to engage community pharmacies in TBPD.MethodsA multicentre cross-sectional study was performed in four areas of Indonesia’s eastern, central and western parts. Pharmacists and pharmacy technicians who worked in community pharmacies were assessed for their characteristics and KAP related to TBPD. Descriptive analysis was used to assess participant characteristics and their KAP, while multivariable regression analyses were used to analyse factors associated with the KAP on TBPD.ResultsA total of 1129 participants from 979 pharmacies, comprising pharmacists (56.6%) and pharmacy technicians (43.4%), were included. Most participants knew about TB. However, knowledge related to TB symptoms, populations at risk and medication for TB were still suboptimal. Most participants showed a positive attitude towards TBPD. They believed in their professional role (75.1%), capacity in TB screening (65.4%) and responsibility for TBPD (67.4%). Nevertheless, a lack of TBPD practice was identified in most participants. Several factors significantly associated with performing the TBPD practice (p<0.05), such as TB training experience (p<0.001), provision of a drug consultation service (p<0.001), male gender (p<0.05), a positive attitude towards TBPD (p<0.001), short working hours (p<0.001) and central city location of the pharmacy (p<0.05).ConclusionsMost participants had good knowledge and attitude, which did not translate into actual TBPD practice. We identified that TB educational programmes are essential in improving the KAP. A comprehensive assessment is needed to develop effective strategies to engage the community pharmacy in TBPD activities.
Associations between WASH-related violence and depressive symptoms in adolescent girls and young women in South Africa (HPTN 068): a cross-sectional analysis
Authors: Jayaweera Ruvani T , Goin Dana , Twine Rhian , Neilands Torsten B , Wagner Ryan G , Lippman Sheri A , Kahn Kathleen , Pettifor Audrey , Ahern Jennifer 
Published: July 2022

ObjectiveThere is a lack of research on experiences of WASH-related violence. This study aims to quantify the association between experience or worry of violence when using the toilet or collecting water and depressive symptoms among a cohort of young women in South Africa.MethodsData are from visit 3 of the HPTN 068 cohort of adolescent girls in rural Mpumalanga Province, South Africa. Participants (n=1798) included in this analysis were aged 13–21 at baseline. Lifetime experience of violence or fear of violence when using the toilet and collecting water was collected by self-report; depressive symptoms in the past week were measured using the Center for Epidemiological Studies Depression Scale (CES-D). We used G-computation to calculate the prevalence difference (PD) and prevalence ratio of depression (CES-D score >15) associated with each domain of violence, controlling for baseline covariates.FindingsA total of 15.1% of respondents reported experiencing violence when using the toilet; 17.1% reported experiencing violence when collecting water and 26.7% reported depression. In adjusted models, those who reported experiencing violence when using the toilet had an 18.1% higher prevalence of depression (95% CI: 11.6% to 24.4%) than those who did not experience violence when using the toilet. Adjusted prevalence of depression was also higher among those who reported violence when collecting water (PD 11.9%, 95% CI: 6.7% to 17.2%), and who worried about violence when using the toilet (PD 12.8%, 95% CI: 7.9% to 19.8%), as compared with those who did not report these experiences. Worrying about violence when collecting water was not associated with depression after adjusting for covariates.ConclusionExperience of WASH-related violence is common among young women in rural South Africa, and experience or worry of experiencing violence is associated with higher prevalence of depressive symptoms.Trial registration numberNCT01233531; Post-results.
Comparisons between biopsy-proven versus clinically diagnosed cardiac sarcoidosis
Authors: Kitai Takeshi , Nabeta Takeru , Naruse Yoshihisa , Taniguchi Tatsunori , Yoshioka Kenji , Miyakoshi Chisato , Kurashima Shinichi , Miyoshi Yutaro , Tanaka Hidekazu , Okumura Takahiro , Baba Yuichi , Furukawa Yutaka , Matsue Yuya , Izumi Chisato 
Published: July 2022

ObjectivesDiagnosis of cardiac sarcoidosis (CS) without histological evidence remains controversial. This study aimed to compare characteristics and outcomes of histologically proven versus clinically diagnosed cases of CS, which were adjudicated using Heart Rhythm Society or Japanese Circulation Society criteria.MethodsA total of 512 patients with CS (age: 62±11 years, female: 64.3%) enrolled in the multicentre registry were studied. Histologically confirmed patients were classified as ‘biopsy-proven CS’, while those with the presence of strongly suggestive clinical findings of CS without histological evidence were classified as ‘clinical CS’. Primary outcome was a composite of all-cause death, heart failure hospitalisation and ventricular arrhythmia event.ResultsIn total, 314 patients (61.3%) were classified as biopsy-proven CS, while 198 (38.7%) were classified as clinical CS. Patients classified under clinical CS were associated with higher prevalence of left ventricular dysfunction, septal thinning, and positive findings in fluorodeoxyglucose-positron emission tomography or Gallium scintigraphy than those under biopsy-proven CS. During median follow-up of 43.7 (23.3–77.3) months, risk of primary outcome was comparable between the groups (adjusted HR: 1.24, 95% CI: 0.88 to 1.75, p=0.22). Similarly, the risks of primary outcome were comparable between patients with clinical isolated CS who did not have other organ/tissue involvement, and biopsy-proven isolated CS (adjusted HR: 1.23, 95% CI: 0.56 to 2.70, p=0.61).ConclusionsA substantial number of patients were diagnosed with clinical CS without confirmatory biopsy. Considering the worse clinical outcomes irrespective of the histological evidence, the diagnosis of clinical CS is justifiable if imaging findings suggestive of CS are observed.
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer
Authors: Kwon Minsuk , Kim Gahyun , Kim Ryul , Kim Kyu-Tae , Kim Seung Tae , Smith Simon , Mortimer Peter G S , Hong Jung Yong , Loembé Arsene-Bienvenu , Irurzun-Arana Itziar , Koulai Loumpiana , Kim Kyoung-Mee , Kang Won Ki , Dean Emma , Park Woong-Yang , Lee Jeeyun 
Published: July 2022

BackgroundTargeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.MethodsThis phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15–28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients.ResultsAmong 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p<0.001). During the study treatment, upregulation of the innate immune response by cytosolic DNA, activation of intratumoral lymphocytes, and expansion of circulating tumor-reactive CD8 +T cell clones were identified in responders. Enrichment of the tumor vasculature signature was associated with treatment resistance.ConclusionsCeralasertib plus durvalumab has promising antitumor activity, with durable responses in patients with refractory AGC. Thus, a biomarker-driven trial is required.Trial registrationNCT03780608.
Quantum gravity on a manifold with boundaries: Schrödinger evolution and constraints
Authors: Rosabal J. A. 
Published: July 2022

AbstractIn this work, we derive the boundary Schrödinger (functional) equation for the wave function of a quantum gravity system on a manifold with boundaries together with a new constraint equation defined on the timelike boundary. From a detailed analysis of the gravity boundary condition on the spatial boundary, we find that while the lapse and the shift functions are independent Lagrange multipliers on the bulk, on the spatial boundary, these two are related; namely, they are not independent. In the Hamiltonian ADM formalism, a new Lagrange multiplier, solving the boundary conditions involving the lapse and the shift functions evaluated on the spatial boundary, is introduced. The classical equation of motion associated with this Lagrange multiplier turns out to be an identity when evaluated on a classical solution of Einstein’s equations. On the other hand, its quantum counterpart is a constraint equation involving the gravitational degrees of freedom defined only on the boundary. This constraint has not been taken into account before when studying the quantum gravity Schrödinger evolution on manifolds with boundaries.
On Finslerian extension of special relativity
Authors: Sagaydak Alina E. , Silagadze Zurab K. 
Published: July 2022

In this paper, we demonstrate that Robb-Geroch’s definition of a relativistic interval admits a simple and fairly natural generalization leading to a Finsler extension of special relativity. Another justification for such an extension goes back to the works of Lalan and Alway and, finally, was put on a solid basis and systematically investigated by Bogoslovsky under the name “Special-relativistic theory of locally anisotropic spacetime”. The isometry group of this spacetime, DISIM[Formula: see text], is a deformation of the Cohen and Glashow’s very special relativity symmetry group ISIM(2). Thus, the deformation parameter [Formula: see text] can be regarded as an analog of the cosmological constant characterizing the deformation of the Poincaré group into the de Sitter (anti-de Sitter) group. The simplicity and naturalness of Finslerian extension in the context of this paper adds weight to the argument that the possibility of a nonzero value of [Formula: see text] should be carefully considered.
PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry
Authors: Patel Amish J. , Warda Sarah , Maag Jesper L.V. , Misra Rohan , Miranda-Román Miguel A. , Pachai Mohini R. , Lee Cindy J. , Li Dan , Wang Naitao , Bayshtok Gabriella , Fishinevich Eve , Meng Yinuo , Wong Elissa W.P. , Yan Juan , Giff Emily , Pappalardi Melissa B. , McCabe Michael T. , Fletcher Jonathan A. , Rudin Charles M. , Chandarlapaty Sarat , Scandura Joseph M. , Koche Richard P. , Glass Jacob L. , Antonescu Cristina R. , Zheng Deyou , Chen Yu , Chi Ping 
Published: July 2022

Abstract

Polycomb repressive complex 2 (PRC2) has oncogenic and tumor-suppressive roles in cancer. There is clinical success of targeting this complex in PRC2-dependent cancers, but an unmet therapeutic need exists in PRC2-loss cancer. PRC2-inactivating mutations are a hallmark feature of high-grade malignant peripheral nerve sheath tumor (MPNST), an aggressive sarcoma with poor prognosis and no effective targeted therapy. Through RNAi screening in MPNST, we found that PRC2 inactivation increases sensitivity to genetic or small-molecule inhibition of DNA methyltransferase 1 (DNMT1), which results in enhanced cytotoxicity and antitumor response. Mechanistically, PRC2 inactivation amplifies DNMT inhibitor–mediated expression of retrotransposons, subsequent viral mimicry response, and robust cell death in part through a protein kinase R (PKR)–dependent double-stranded RNA sensor. Collectively, our observations posit DNA methylation as a safeguard against antitumorigenic cell-fate decisions in PRC2-loss cancer to promote cancer pathogenesis, which can be therapeutically exploited by DNMT1-targeted therapy.

Significance:
PRC2 inactivation drives oncogenesis in various cancers, but therapeutically targeting PRC2 loss has remained challenging. Here we show that PRC2-inactivating mutations set up a tumor context–specific liability for therapeutic intervention via DNMT1 inhibitors, which leads to innate immune signaling mediated by sensing of derepressed retrotransposons and accompanied by enhanced cytotoxicity.
See related commentary by Guil and Esteller, p. 2020.
This article is highlighted in the In This Issue feature, p. 2007
FMO2 (Flavin Containing Monooxygenase 2) Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis
Authors: Ni Cheng , Chen Yongjian , Xu Yinchuan , Zhao Jing , Li Qingju , Xiao Changchen , Wu Yan , Wang Jingyi , Wang Yingchao , Zhong Zhiwei , Zhang Ling , Wu Rongrong , Liu Qingnian , Wu Xianpeng , Ke Changle , Zhu Wei , Chen Jinghai , Huang Jijun , Wang Yibin , Wang Jian’an , Hu Xinyang 
Published: July 2022

Background:
Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown.

Methods:

Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using
postn
-promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI.

Results:
A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 (small mothers against decapentaplegic 2/3) phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling.

Conclusions:
Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.
Dogs in the Islamic Tradition: A Revisionist Examination
Authors: Polinsky Sheridan 
Published: July 2022

Abstract
This article examines the roles and representations of dogs in Islam by focusing on their place in four manifestations of the Islamic tradition: the Quran, Islamic jurisprudence, Muḥammad al-Damīrī’s The Great Life of Animals, and Sufism. Whereas many Muslims and non-Muslims alike believe that dogs have a low status in Islam, these four sources offer an abundance of positive material about the canine that challenges this view. They also reveal that Muslim scholars have debated much of the contentious material concerning dogs, often forming opinions in response to it that are favorable to the creature. Paying greater attention to the nuances and complexity of the discourses on dogs and their images within the Islamic tradition can help improve understanding of dogs therein and inspire dog-friendly attitudes among modern Muslims.