bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of AITC‐induced dermal blood flow as a translational in vivo biomarker of TRPA1 activity in human and rodent skin
Authors: Joseph Victory , Yang Xiaoying , Gao Simon S. , Elstrott Justin , Weimer Robby M. , Theess Wiebke , Thrasher Cory , Singh Nand , Lin Joseph , Bauer Rebecca N. 
Published: May 2020

Background and PurposeDevelop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker.Experimental ApproachAllyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1‐knock out (Trpa1 KO) rats, and changes in dermal blood flow (DBF) were measured by laser speckle contrast imaging. In humans, the DBF, pain and itch responses to 5‐20% AITC applied to the forearm were measured and safety was evaluated. Reproducibility of the DBF, pain and itch responses to topically applied 10% and 15% AITC were assessed at two visits separated by 13‐15 days. DBF changes were summarized at 5‐minute intervals as areas under the curve (AUC) and maxima. Intraclass correlation coefficient (ICC) was calculated to assess arm‐arm and period‐period reproducibility.Key ResultsAITC‐ and citric acid‐induced DBF were significantly reduced in Trpa1 KO rats compared to wildtype (90 ± 2% and 65 ± 11% reduction, respectively), whereas capsaicin response did not differ. In humans, each AITC concentration significantly increased DBF compared to vehicle with the maximal increase occurring 5 minutes post application. Ten percent and 15% AITC were selected as safe and effective stimuli. AUC from 0 to 5 minutes was the most reproducible metric of AITC‐induced DBF across arms (ICC = 0.92) and periods (ICC = 0.85). Subject‐reported pain was more reproducible than itch across visits (ICC = 0.76 vs 0.17, respectively).Conclusion and ImplicationsAITC‐induced DBF is a suitable target engagement biomarker of TRPA1 activity for preclinical and clinical studies of TRPA1 antagonists.
Allostatic load, emotional hyper‐reactivity, and functioning in individuals with bipolar disorder
Authors: Dargél Aroldo A. , Volant Stevenn , Brietzke Elisa , Etain Bruno , Olié Emilie , Azorin Jean‐Michel , Gard Sebastian , Bellivier Frank , Bougerol Thierry , Kahn Jean‐Pierre , Roux Paul , Aubin Valerie , Courtet Philippe , Leboyer Marion , Henry Chantal ,   The FACE‐BD collaborators
Published: May 2020

AbstractObjectivesDiagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter‐episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic dysregulation and functional impairment.MethodsLevels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper‐reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data‐driven biomarker selection.ResultsBALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper‐reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper‐reactivity had significantly lower global and cognitive functioning than those without emotional hyper‐reactivity (P < .0001).ConclusionsA multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper‐reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic disturbances and functional impairment.
Cross‐sector alliances in the global refugee crisis: An institutional theory approach
Authors: Yang Aimei , Liu Wenlin , Wang Rong 
Published: May 2020

AbstractThe global refugee crisis has posed severe challenges to social stability and sustainable development around the world. While the business sector is expected to shoulder social responsibility in crisis relief efforts, our initial assessment shows that refugee‐related corporate social responsibility (CSR) significantly diverged across the Global Fortune 500 corporations. To advance scholars and managers' understanding of this complex CSR issue, this study draws upon National Business System Theory to explore how country‐level factors influence the multinational corporations' CSR communication about the refugee issue. Specifically, the study focuses on the strategic cross‐sector alliances between corporations, NGOs, and IGOs. The analysis shows that in this controversial global crisis, the following factors of corporations' countries‐of‐origin can significantly affect the level of cross‐sector CSR alliances: democracy levels, economic inequality levels, and unemployment rates. Findings of this study provide practical guidelines that can help managers to anticipate societal expectations when dealing with controversial social issues in an international setting. Our findings could also assist policymakers, NGOs, and IGOs to better design strategies to mobilize the corporate resources.
Iterated multisource exchangeability models for individualized inference with an application to mobile sensor data
Authors: Brown Roland , Fan Yingling , Das Kirti , Wolfson Julian 
Published: May 2020

AbstractResearchers are increasingly interested in using sensor technology to collect accurate activity information and make individualized inference about treatments, exposures, and policies. How to optimally combine population data with data from an individual remains an open question. Multisource exchangeability models (MEMs) are a Bayesian approach for increasing precision by combining potentially heterogeneous supplemental data sources into analysis of a primary source. MEMs are a potentially powerful tool for individualized inference but can integrate only a few sources; their model space grows exponentially, making them intractable for high‐dimensional applications. We propose iterated MEMs (iMEMs), which identify a subset of the most exchangeable sources prior to fitting a MEM model. iMEM complexity scales linearly with the number of sources, and iMEMs greatly increase precision while maintaining desirable asymptotic and small sample properties. We apply iMEMs to individual‐level behavior and emotion data from a smartphone app and show that they achieve individualized inference with up to 99% efficiency gain relative to standard analyses that do not borrow information.
Estimating and inferring the maximum degree of stimulus‐locked time‐varying brain connectivity networks
Authors: Tan Kean Ming , Lu Junwei , Zhang Tong , Liu Han 
Published: May 2020

AbstractNeuroscientists have enjoyed much success in understanding brain functions by constructing brain connectivity networks using data collected under highly controlled experimental settings. However, these experimental settings bear little resemblance to our real‐life experience in day‐to‐day interactions with the surroundings. To address this issue, neuroscientists have been measuring brain activity under natural viewing experiments in which the subjects are given continuous stimuli, such as watching a movie or listening to a story. The main challenge with this approach is that the measured signal consists of both the stimulus‐induced signal, as well as intrinsic‐neural and nonneuronal signals. By exploiting the experimental design, we propose to estimate stimulus‐locked brain networks by treating nonstimulus‐induced signals as nuisance parameters. In many neuroscience applications, it is often important to identify brain regions that are connected to many other brain regions during cognitive process. We propose an inferential method to test whether the maximum degree of the estimated network is larger than a prespecific number. We prove that the type I error can be controlled and that the power increases to one asymptotically. Simulation studies are conducted to assess the performance of our method. Finally, we analyze a functional magnetic resonance imaging dataset obtained under the Sherlock Holmes movie stimuli.
The revised Psychosis Attachment Measure: Measuring disorganized attachment
Authors: Pollard Catherine , Bucci Sandra , MacBeth Angus , Berry Katherine 
Published: May 2020

ObjectivesThe Psychosis Attachment Measure (PAM) is currently the most widely used and validated measure of attachment in psychosis. However, the PAM does not assess disorganized attachment, the type of attachment that has been most closely linked with vulnerability to psychosis. This study aimed to expand the PAM to capture the concept of disorganized attachment and to examine its psychometric properties in a psychosis sample.MethodsClinical and academic experts in the field of psychosis and service user representatives were asked to assess the comprehensiveness and comprehensibility of the pool of disorganized items. This process resulted in 12 items hypothesized to capture disorganized attachment that were included with the original items of the PAM. A sample of 144 individuals with either a self‐reported diagnosis of, or treatment for, a psychosis‐related condition completed a battery of online measures comprising the revised PAM, existing measures of adult disorganized attachment and constructs hypothesized to be conceptually related to disorganized attachment.ResultsAn exploratory factor analysis was conducted with three factors retained; these were labelled anxious, avoidant and disorganized attachment. The factors displayed good internal consistency and test–retest reliability and the disorganized factor displayed good construct validity with related measures and constructs.ConclusionsThese results provide preliminary evidence that the revised PAM captures the concept of disorganized attachment. However, confirmatory psychometric evaluation of the revised PAM is required, within a separate psychosis sample, to confirm its factor structure. The relationship between these results and the current literature, in addition to the clinical and research implications, are discussed.Practitioner points

We present an expanded version of the Psychosis Attachment Measure (PAM), revised to capture the concept of disorganised attachment in adulthood. This expanded measure showed good reliability and the new disorganized subscale demonstrated construct validity.

These results provide preliminary evidence that disorganized attachment can be measured using a simple self‐report measure with individuals with psychosis.

Further research is required to confirm the structural dimensionality of the revised PAM within a new sample using confirmatory factor analysis.

Following further psychometric validation the use of this measure has the potential to be expanded to other mental health conditions in which disorganized attachment has been implicated in the development and maintenance of difficulties, for example, trauma‐related conditions and borderline personality disorder.
Low educational level of head of household, as a proxy for poverty, is associated with severe anaemia among children with sickle cell disease living in a low‐resource setting: evidence from the SPRING trial
Authors: Bello‐Manga Halima , Galadanci Aisha A. , Abdullahi Shehu , Ali Shehi , Jibir Binta , Gambo Safiya , Haliru Lawal , Jordan Lori C. , Aliyu Muktar H. , Rodeghier Mark , Kassim Adetola A. , DeBaun Michael R. , Galadanci Najibah A. 
Published: May 2020

SummarySevere anaemia, defined as haemoglobin level < 6·0 g/dl, is an independent risk factor for death in individuals with sickle cell disease living in resource‐limited settings. We conducted a cross‐sectional study of 941 children with sickle cell anaemia, who had been defined as phenotype HbSS or HbSβ0 thalassaemia, aged five to 12 years, and were screened for enrollment into a large primary stroke prevention trial in Nigeria (SPRING; NCT02560935). The main aim of the study was to determine the prevalence and risk factors for severe anaemia. We found severe anaemia to be present in 3·9% (37 of 941) of the SPRING study participants. Severe anaemia was significantly associated with the lower educational level of the head of the household (P = 0·003), as a proxy for poverty, and a greater number of children per room in the household (P = 0·004). Body mass index was not associated with severe anaemia. The etiology of severe anaemia in children living with sickle cell anaemia in Nigeria is likely to be multifactorial with an interplay between an individual's disease severity and other socio‐economic factors related to poverty.
Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam
Authors: Hughes Dyfrig A. 
Published: May 2020

Background and PurposeResurgence in the use of chloroquine as a potential treatment for COVID‐19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity.Experimental ApproachIn vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine alone or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone‐anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5‐4864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane‐anaesthetised rats and (vi) co‐administered with adrenaline.Key ResultsChloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose‐dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments and control. Diazepam increased heart rate in study (iv) and as with clonazepam also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia.Conclusion and ImplicationsNeither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity.Linked ArticlesThis article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Potential role of transforming growth factor‐beta 1/Smad signaling in secondary lymphedema after cancer surgery
Authors: Sano Masaki , Hirakawa Satoshi , Suzuki Minoru , Sakabe Jun‐ichi , Ogawa Mikako , Yamamoto Seiji , Hiraide Takanori , Sasaki Takeshi , Yamamoto Naoto , Inuzuka Kazunori , Tanaka Hiroki , Saito Takaaki , Sugisawa Ryota , Katahashi Kazuto , Yata Tatsuro , Kayama Takafumi , Urano Tetsumei , Tokura Yoshiki , Sato Kohji , Setou Mitsutoshi , Takeuchi Hiroya , Konno Hiroyuki , Unno Naoki 
Published: May 2020

AbstractSecondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor‐beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast‐dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery.
Associations of Japanese food intake with survival of stomach and colorectal cancer: A prospective patient cohort study
Authors: Minami Yuko , Kanemura Seiki , Oikawa Tomoyuki , Suzuki Shinichi , Hasegawa Yasuhiro , Nishino Yoshikazu , Fujiya Tsuneaki , Miura Koh 
Published: May 2020

AbstractDietary factors may affect the prognosis of digestive tract cancer, but evidence has been sparse. We investigated the association between pretreatment intake of 6 Japanese foods (including soy food, miso [soybean paste] soup and seaweed) and the risk of death among patients with histologically confirmed major digestive tract cancers (stomach, 1931; colon, 793; rectum, 510) diagnosed during 1997‐2013 at a single institution in Japan. Pretreatment dietary intake was assessed using a food frequency questionnaire, and the patients were followed until December 2016. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Among the patients with stomach cancer, frequent intake of soy food was inversely associated with the risk of all‐cause (Ptrend for four frequency groups = 0.01; HR = 0.72, 95% CI: 0.50‐1.04 for highest vs lowest group) and stomach cancer (Ptrend = 0.03; HR = 0.63, 95% CI: 0.40‐0.99) death. A similar inverse association was also found for intake of miso soup. In contrast, frequent seaweed intake was inversely associated with the risk of all‐cause death among the patients with colon cancer (Ptrend = 0.03). Rectal cancer patients who had frequently consumed seaweed tended to have a lower risk of rectal cancer death (Ptrend = 0.02). These findings indicate that pretreatment intake of Japanese foods such as soybean products and seaweed may have favorable effects on patient survival of stomach and colorectal cancer, although this needs to be confirmed by further research.
Identification of an ATP metabolism‐related signature associated with prognosis and immune microenvironment in gliomas
Authors: Huang Ruoyu , Li Guanzhang , Wang Zhiliang , Hu Huimin , Zeng Fan , Zhang Kenan , Wang Kuanyu , Wu Fan 
Published: May 2020

AbstractAs the core element of material and energy metabolism pathways, the biological functions and prognostic significance of ATP metabolism in diffuse gliomas have so far remained unclear. Based on comprehensive analysis of ATP metabolism‐related gene expression profiles, we constructed an ATP metabolism‐related risk signature to determine the role of ATP metabolism. We found that this ATP metabolism‐related gene expression profile could divide patients into 2 robust groups with distinct clinical characteristics and prognosis. Patients in the high‐risk group tended to be predicted as malignant entities, indicating that the activation of ATP metabolism may promote the malignant progress of diffuse gliomas. Cox regression and Kaplan‐Meier analyses suggested that this risk signature was an independent predictor for prognosis. Furthermore, we constructed an individualized prognosis prediction model through nomogram and time‐dependent receiver operating characteristic (ROC) curve analyses. Functional analysis suggested that, in addition to material and energy metabolism, ATP metabolism also played an essential role in the regulation of the tumor immune microenvironment. In brief, the ATP metabolism‐related signature was tightly associated with regulation of the tumor immune microenvironment and could serve as an independent prognostic biomarker in diffuse gliomas.
Thymidylate synthase inhibitor raltitrexed can induce high levels of DNA damage in MYCN‐amplified neuroblastoma cells
Authors: Yamashita Ken , Kiyonari Shinichi , Tsubota Shoma , Kishida Satoshi , Sakai Ryuichi , Kadomatsu Kenji 
Published: May 2020

AbstractMYCN gene amplification is consistently associated with poor prognosis in patients with neuroblastoma, a pediatric tumor arising from the sympathetic nervous system. Conventional anticancer drugs, such as alkylating agents and platinum compounds, have been used for the treatment of high‐risk patients with MYCN‐amplified neuroblastoma, whereas molecule‐targeting drugs have not yet been approved. Therefore, the development of a safe and effective therapeutic approach is highly desired. Although thymidylate synthase inhibitors are widely used for colorectal and gastric cancers, their usefulness in neuroblastoma has not been well studied. Here, we investigated the efficacies of approved antifolates, methotrexate, pemetrexed, and raltitrexed (RTX), on MYCN‐amplified and nonamplified neuroblastoma cell lines. Cell growth‐inhibitory assay revealed that RTX showed a superior inhibitory activity against MYCN‐amplified cell lines. We found no significant differences in the protein expression levels of the antifolate transporter or thymidylate synthase, a primary target of RTX, among the cell lines. Because thymidine supplementation could rescue the RTX‐induced cell growth suppression, the effect of RTX was mainly due to the reduction in dTTP synthesis. Interestingly, RTX treatments induced single‐stranded DNA damage response in MYCN‐amplified cells to a greater extent than in the nonamplified cells. We propose that the high DNA replication stress and elevated levels of DNA damage, which are a result of deregulated expression of MYCN target genes, could be the cause of increased sensitivity to RTX.