bluuebunny/crossref_metadata_2025_split huggingface dataset:
Floods, food security, and coping strategies: Evidence from Afghanistan
Authors: Oskorouchi Hamid R. , Sousa‐Poza Alfonso 
Published: January 2021

AbstractIn this paper, we assess the long‐term effect of floods on food security (as measured by calorie and micronutrient consumption) by applying an instrumental variable approach to data from the Afghanistan National Risk and Vulnerability Assessment survey. To identify the determinants of this effect, we also estimate how floods affect per capita yearly household income and poverty status. We find that exposure to flooding during a 12‐month period decreased daily calorie consumption by approximately 60 kcal while increasing the probability of iron, vitamin A, and vitamin C deficiency by 11, 12, and 27 percentage points, respectively. Controlling for price shocks and income only marginally reduces this flood effect on food security, suggesting that impaired livelihoods (rather than price hikes) are its primary driver. We further determine that exposure to this natural disaster decreases income by about 3% and makes flood‐affected households about 3 percentage points more likely to be poor. Lastly, we show that experience of floods is strongly and significantly associated with lower diet quality and quantity, and with engaging in consumption smoothing coping strategies, such as buying food on credit and taking loans. These findings underscore the serious direct impact of floods on both diet and effective behavioral responses to such shocks while emphasizing the need for targeted micronutrient supplementation in disaster relief and food aid measures even after the period of natural disaster emergency.
Effect of lipophilicity on drug distribution and elimination: Influence of obesity
Authors: Bruno Christopher D. , Harmatz Jerold S. , Duan Su X. , Zhang Qingchen , Chow Christina R. , Greenblatt David J. 
Published: January 2021

AimsFor a given passively‐distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, Vd) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in Vd associated with obesity across a series of drugs.MethodsCohorts of normal‐weight control and obese subjects received single doses of drugs ranging from hydrophilic (acetaminophen, salicylate) to lipophilic (imipramine, verapamil). Lipid solubility was measured by the log‐transformed values of the high‐pressure liquid chromatographic (HPLC) retention index (Log10(HPLC)), and the octanol–water partition coefficient (LogP).ResultsAmong normal‐weight controls, Vd normalized for protein binding was highly correlated with Log10(HPLC) (R2 = .65) and with LogP (R2 = .78). Vd of all drugs was increased in the obese cohort, but the relative increase (compared to controls) for individual drugs was disproportionately greater as lipid solubility increased. Since clearance was unrelated to lipophilicity, the increased Vd produced a parallel disproportionate increase in elimination half‐life in the obese cohort that was associated with Log10(HPLC) (R2 = .62).ConclusionLipophilicity is a principal correlate of in vivo Vd, as well as the increased Vd of drugs in obese patients. The consequent prolongation of half‐life in obesity has clinical safety implications in terms of delayed drug accumulation and washout during and after chronic dosage. The magnitude and importance of this effect for a given drug depends on the degree of obesity, as well as the lipid‐solubility of the specific drug.
The association between manic symptoms in adolescence and preschool symptoms: The importance of family history
Authors: Charatcharungkiat Natchanan , Luby Joan , Tillman Rebecca , Vogel Alecia 
Published: January 2021

AbstractObjectivesFirst, to investigate whether specific manic symptoms in preschool predict manic symptom severity in adolescence. Second, to investigate the interaction between family history (FH) of bipolar disorder (BP) and preschool manic symptoms in predicting later adolescent manic symptom severity.MethodsThis analysis utilized data from the Preschool Depression Study (PDS) which followed 306 preschoolers aged 3–6 years over time since 2003. Only subjects who had data both at baseline (age 3–6 years) and at or after age 12 were included (n = 122). Baseline manic symptom severity scores and diagnoses were assessed by the Preschool Age Psychiatric Assessment (PAPA). Manic symptoms severity at age ≥12 was assessed by the Kiddie Mania Rating Scale (KMRS). FH were ascertained by Family Interview for Genetic Studies (FIGS). Multilevel models of KMRS total score at age ≥12 by preschool mania symptoms with gender, baseline age, baseline ADHD, as well as baseline MDD diagnosis as covariates, and false discovery rate correction were used in statistical analysis.ResultsHypertalkativity, flight of ideas, uninhibited gregariousness, decreased need for sleep (DNFS), and increased motor pressure/ motor activity/ energy in preschool were associated with increased KMRS score at age ≥12. Racing thoughts, inappropriate laughing, and DNFS in early childhood were associated with higher manic symptoms in adolescence in subjects with FH of BP compared to those without FH.ConclusionThe longitudinal clinical importance of displaying manic symptoms (racing thoughts, inappropriate laughing, and DNFS) in early childhood varies by FH. Among the aforementioned symptoms, DNFS was a robust predictor of later manic symptoms. Assessing FH of BP is very important in clinical risk prediction from early childhood.
Using assistive technology with SRSD to support students on the autism spectrum with persuasive writing
Authors: Ozdowska Anne , Wyeth Peta , Carrington Suzanne , Ashburner Jill 
Published: January 2021

AbstractChildren on the autism spectrum (AS) often struggle with writing tasks at school. They commonly experience difficulty with two key aspects of writing: the skills required for handwriting (fine motor and perceptual) and the conceptual and language skills required for written composition. Specialist intervention to assist with written expression is, therefore, often needed for students on the AS to succeed academically. This research evaluated the impact of using self‐regulated strategy development (SRSD) in combination with assistive technology on the quality and length of written compositions of students on the AS. It also investigated how students felt about using the SRSD writing strategy. Eight primary school students on the AS between the ages of 9 and 12 participated in this single‐subject study. An ABAC study design was used to evaluate student writing performance across three conditions. Baseline handwriting measurements were collected during condition A. During condition B students used assistive technology alone; in condition C, students applied their understanding of SRSD while using assistive technology. Results from this study show that, in many cases, the quality and/or length of written compositions and feelings of self‐efficacy towards persuasive writing of students on the AS improved when they received physical and/or conceptual writing supports. This paper presents the research design, methods and results from this single‐subject study followed by a discussion of the results and final thoughts and areas for future research.
Practitioner NotesWhat is already known about this topic?

There is limited research about how the persuasive writing of students on the autism spectrum (AS) can be supported in a socially inclusive way.
Research has shown that the use of assistive technologies like keyboards and writing‐support software can improve the writing outcomes of students on the AS.
Research has shown that the use of self‐regulated strategy development (SRSD) writing strategies can improve the persuasive writing outcomes of diverse students.
What this paper adds?

A single‐subject study using an ABAC study design showed that persuasive writing outcomes improved in quality or length for some students when they used an app that combined the two strategies.
Implications for policy and practice

SRSD combined with writing‐support software appeared to improve the writing outcomes of some students on the AS. It can, therefore, be used as a tool to support teachers in developing strategies for inclusive classrooms.
Examining the relational underpinnings and consequences of system‐justifying beliefs: Explaining the palliative effects of system justification
Authors: Bahamondes Joaquín , Sengupta Nikhil K. , Sibley Chris G. , Osborne Danny 
Published: January 2021

People often perceive social systems as fair and legitimate in order to satisfy existential, epistemic, and relational needs. Although much work has examined the existential and epistemic roots to system justification, the relational motives underlying the tendency to justify the system have received comparatively less attention. We addressed this oversight by examining the associations approach and avoidance relational goals have with system justification in a national probability sample (N = 21,938). Consistent with the thesis that the need to belong motivates system justification, avoidance goals (i.e., the desire to avoid social conflict) correlated positively with system justification (approach goals also unexpectedly correlated positively with system justification). Also as hypothesized, system justification mediated the relationship between avoidance goals and belongingness. Moreover, system justification mediated the relationship between avoidance goals and belongingness. Finally, sequential mediation analyses revealed that avoidance goals predicted higher well‐being via system justification and belongingness. This study is the first to demonstrate that system justification confers palliative benefits by satisfying two different relational goals.
More than words: Foreign exchange intervention under imperfect credibility
Authors: Gomez‐Gonzalez Jose Eduardo , Parra‐Polania Julian Andres , Villamizar‐Villegas Mauricio 
Published: January 2021

AbstractCentral banks in emerging countries frequently build‐up (diminish) reserves while attempting to depreciate (appreciate) their currencies. Even if these interventions are effective, they often entail various costs. Basu (2012), nonetheless, proposes a model in which the sole announcement of an intervention schedule leads to a desired exchange rate without actually buying or selling foreign currency. In this paper, we present a generalization that allows for imperfect credibility of promises. Namely, market dealers know that the central bank carries strategic incentives when announcing its schedule and may not perfectly believe it. We show that, under this setup, it may be impossible to achieve the targeted rate without changing the level of international reserves. However, committing to a schedule, despite being imperfectly credible, outperforms unannounced discretionary interventions. This is the case because it reduces the amount of foreign currency trading required for a central bank to meet its desired exchange rate.
M351‐0056 is a novel low MW compound modulating the actions of the immune‐checkpoint protein VISTA
Authors: Hu Xinlei , Qie Chenxin , Jiang Jingwei , Xie Xiaoxue , Chen Wenting , Liu Wanmei , Liu Jun 
Published: January 2021

Background and PurposeThe protein V‐domain immunoglobulin suppressor of T‐cell activation (VISTA) is a novel immune‐checkpoint molecule that belongs to the B7 family and regulates a broad spectrum of immune responses. So far, low MW compounds targeting VISTA for the treatment of autoimmune diseases or inflammation, have not been identified.Experimental ApproachWe developed a homology modelling for VISTA 3D structure and subsequent virtual screening for low MW ligands binding to VISTA. Visualization of the binding postures of docked ligands with protein VISTA indicated that compound M351‐0056 targeted VISTA. The biological activities of compound M351‐0056 targeting VISTA were investigated in vitro using monocytes and T cells and in vivo, using mice with imiquimod‐induced dermatitis.Key ResultsThe KD value of M351‐0056 for human VISTA‐extracellular domain was 12.60 ± 3.84 μM as assessed by microscale thermophoresis. M351‐0056 decreased cytokine secretion from PBMCs or human CD4+ T cells, suppressed proliferation of PBMCs and enhanced expression of Foxp3+ T cells. These effects of M351‐0056 modulating VISTA involved the JAK2–STAT2 pathway. Daily administration of M351‐0056 ameliorated imiquimod‐induced psoriasis‐like dermatitis. Expression of mRNA and protein of inflammatory cytokines in psoriatic lesions was decreased after M351‐0056 treatment.Conclusion and ImplicationsThe compound M351‐0056 showed high affinity for VISTA and may modulate its immune function in vitro and in vivo. Our finding provides a lead compound for therapeutically enhancing VISTA‐mediated pathways to benefit the treatment of autoimmune diseases or inflammation.
Vascular biotransformation of organic nitrates is independent of cytochrome P450 monooxygenases
Authors: Lopez Melina , Malacarne Pedro F. , Gajos‐Draus Anna , Ding Xinxin , Daiber Andreas , Lundberg Jon O. , Offermanns Stefan , Brandes Ralf P. , Rezende Flávia 
Published: January 2021

Background and PurposeOrganic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina or ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) or cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic nitrates in vessels, the contribution of vascular CYPs is unknown and was studied here.Experimental ApproachAs all CYPs depend on cytochrome P450 reductase (POR) as electron donor, we generated a smooth muscle cell‐specific, inducible knockout mouse of POR (smcPOR−/−) to investigate the contribution of POR/CYP to vascular biotransformation of organic nitrates.Key ResultsMicrosomes containing recombinant CYPs expressed in human vascular tissues released nitrite from NTG and PETN with CYP2C9 and CYP2C8 being most efficient. SFK525, a CYP suicide inhibitor, blocked this effect. smcPOR−/− mice exhibited no obvious cardiovascular phenotype (normal cardiac weight and endothelium‐dependent relaxation) and plasma and vascular nitrite production was similar to control (CTL) animals. NTG‐ and PETN‐induced relaxation of isolated endothelium‐intact or endothelium‐denuded vessels were identical between CTL and smcPOR−/−. Likewise, nitrite release from organic nitrates in aortic rings was not affected by deletion of POR in smooth muscle cells (SMCs). In contrast, inhibition of ALDH2 by benomyl (10 μM) inhibited NTG‐induced nitrite production and relaxation. Deletion of POR did not modulate this response.Conclusions and ImplicationsOur data suggest that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates.
Phase II study of temozolomide monotherapy in patients with extrapulmonary neuroendocrine carcinoma
Authors: Kobayashi Noritoshi , Takeda Yuma , Okubo Naoki , Suzuki Akihiro , Tokuhisa Motohiko , Hiroshima Yukihiko , Ichikawa Yasushi 
Published: January 2021

AbstractExtrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum‐based chemotherapy is used as the standard first‐line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second‐line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum‐based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200 mg/m2 dose of TMZ was given from day 1 to day 5, every 4 weeks. Response rate (RR) was evaluated as the primary end‐point. The presence of O6‐methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n = 3), stomach (n = 3), duodenum (n = 1), colon (n = 1), gallbladder (n = 1), liver (n = 1), uterus (n = 1), bladder (n = 1), and primary unknown (n = 1). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and/or biopsied specimens. The median Ki‐67 labeling index was 60% (range, 22%‐90%). The RR was 15.4%, progression‐free survival was 1.8 months (95% confidence interval [CI], 1.0‐2.7), overall survival (OS) was 7.8 months (95% CI, 6.0‐9.5), and OS from first‐line treatment was 19.2 months (95% CI, 15.1‐23.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum‐based chemotherapy, especially those with MGMT deficiency.
Inhibition of vascular adhesion protein‐1 enhances the anti‐tumor effects of immune checkpoint inhibitors
Authors: Kinoshita Tomonari , Sayem Mohammad Abu , Yaguchi Tomonori , Kharma Budiman , Morii Kenji , Kato Daiki , Ohta Shigeki , Mashima Yukihiko , Asamura Hisao , Kawakami Yutaka 
Published: January 2021

AbstractModulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti‐tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein‐1 (VAP‐1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP‐1 in TME was investigated in 2 murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP‐1‐specific inhibitor U‐V296 inhibited murine tumor growth by enhancing IFN‐γ‐producing tumor antigen‐specific CD8+ T cells. U‐V296 exhibited significant synergistic anti‐tumor effects with ICIs. In the TME of mice treated with U‐V296, the expression of genes associated with M2‐like macrophages, Th2 cells (Il4, Retnla, and Irf4), angiogenesis (Pecam1), and fibrosis (Acta2, Loxl2) were significantly decreased, and the Th1/Th2 balance was increased. H2O2, an enzymatic product of VAP‐1, which promoted the production of IL‐4 by mouse Th2 and inhibited IFN‐γ by mouse Th1 and human tumor‐infiltrating lymphocytes, was decreased in tumors and CD31+ tumor vascular endothelial cells in the TMEs of mice treated with VAP‐1 inhibitor. TCGA database analysis showed that VAP‐1 expression was a negative prognostic factor in human cancers, exhibiting a significant positive correlation with IL‐4, IL4R, and IL‐13 expression and a negative correlation with IFN‐γ expression. These results indicated that VAP‐1 is involved in the immunosuppressive TMEs through H2O2‐associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.
Endoscopic evaluation of pharyngeal and laryngeal sensation in patients with chronic obstructive pulmonary disease (COPD): A cross‐sectional study
Authors: Borowsky da Rosa Fernanda , Schuch Luiz H. , Pasqualoto Adriane S. , Steele Catriona M. , Mancopes Renata 
Published: January 2021

AbstractObjectiveTo describe and compare the findings of endoscopic sensory assessment in COPD patients and healthy controls.DesignA prospective cross‐sectional study.SettingOtorhinolaryngology outpatient clinic at a university hospital.Participants27 adults with COPD and 11 age‐matched healthy controls.Main outcome measuresGroup differences in light touch endoscopic tests of pharyngeal and laryngeal sensation, controlling for pooled salivary secretions in the pharynx and laryngo‐pharyngeal reflux as measured by the Reflux Finding Score (RFS).ResultsA significant difference in laryngeal sensation was found between the study groups (P = .047), with reduced laryngeal sensation in the COPD patients. Additionally, a significant relationship was found between impaired oropharyngeal sensation and the presence of pooled salivary secretions in the pharynx (P = .018), especially in the pyriform sinuses (P = .012). No differences in the frequency of abnormal RFSs were found between groups.ConclusionIndividuals with COPD were significantly more likely to present with impaired laryngeal sensation. Additionally, impaired sensation in the oropharynx was associated with pooled salivary secretions in the pharynx.
Admission avoidance in acute epistaxis: A prospective national audit during the initial peak of the COVID‐19 pandemic
Authors:   INTEGRATE (The UK ENT Trainee Research Network)
Published: January 2021

AbstractObjectivesTo report changes in practice brought about by COVID‐19 and the implementation of new guidelines, and to explore factors relating to unscheduled re‐presentations for patients discharged from the emergency department (ED).DesignProspective multicentre national audit over 12 weeks from 6th April 2020.SettingUK secondary care ENT departments.ParticipantsAdult patients with acute epistaxis.Main outcome measuresRe‐presentation within 10 days for patients discharged from the ED.ResultsEighty three centres from all four UK nations submitted 2631 valid cases. The majority of cases were ED referrals (89.7%, n = 2358/2631). 54.6% were discharged from the ED following ENT review (n = 1267/2322), of whom 19.5% re‐presented within 10 days (n = 245/1259) and 6.8% were ultimately admitted (n = 86/1259). 46.7% of patients had a non‐dissolvable pack inserted by ED prior to referral to ENT (n = 1099/2355). The discharge rates for ED patients and their subsequent re‐presentation rates were as follows: non‐dissolvable packs, 29.5% discharged (n = 332/1125), 18.2% re‐presented (n = 60/330); dissolvable products, 71.1% discharged (n = 488/686), 21.8% re‐presented (n = 106/486); cautery only, 89.2% discharged (n = 247/277), 20.0% re‐presented (n = 49/245); and no intranasal intervention, 85.5% discharged (n = 200/234), 15.2% re‐presented (n = 30/198). Univariable logistic regression showed that not being packed by ED, antiplatelet medications, failed cautery and recent epistaxis treatment were significant predictors of re‐presentation within 10 days.ConclusionsManagement of acute epistaxis was notably affected during the initial peak of the pandemic, with a shift towards reduced admissions. This national audit highlights that many patients who may previously have been admitted to hospital may be safely discharged from the ED following acute epistaxis.