bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐Based Design of 2‐Aminopyrazolpyrimidopyridone Derivatives as New Rearranged During Transfection (RET) Kinase Inhibitors
Authors: Shen Jiayi , Liu Jihu , Tan Zhiyong , Li Anzhi , Chen Sheng , Li Yongdong 
Published: December 2024

ABSTRACTRET (Rearranged during transfection) kinase is a validated target for non‐small cell lung cancer (NSCLC). In 2020, two selective RET inhibitors, selpercatinib and pralsetinib were approved by the US FDA. However, high treatment costs and clinically acquired resistance (e.g., G810C/S/R) become the new challenges for RET‐based therapies. In this work, we discovered a series of 2‐aminopyrazolpyrimidopyridone RET inhibitors to overcome the V804M and G810C resistant mutations. One of the compounds, 8w, exhibited inhibitory potency against the BaF3 cells harboring CCDC6‐RETV804M mutation with an IC50 value of 0.715 μM. The compound also dose‐dependently suppressed the activation of RET and downstream signals. Another compound, 8s suppressed BaF3 cells harboring CCDC6‐RETG810C mutation with an IC50 value of 2.91 μM. However, the poor solubility of these compounds will limit their further development. Therefore, compound 8w and 8s might be promising lead compounds for the development of novel RETV804M and RETG810C inhibitors overcoming the clinically acquired resistance.
Local Application of Honey for Postoperative Pain Management and Associated Outcomes Following Tonsillectomy in Children: A Systematic Review and Meta‐Analysis
Authors: Hosseini Seyed Javad , Hosseini Seyed Reza , Jamshidbeigi Amirreza , Mahmoodi‐Shan Gholam Reza , Hajiabadi Fatemeh , Abdollahi Masoud , Firooz Mahbobeh 
Published: December 2024

ABSTRACTBackgroundThis study investigates the effect of locally applied honey on pain intensity, analgesia consumption, pain relief and nighttime awakenings in children following tonsillectomy, addressing conflicting evidence and the lack of differentiation between adult and paediatric populations in previous reviews.MethodsA systematic search was conducted across multiple databases, including Cochrane Library, ClinicalTrials.gov, MEDLINE, Web of Science and Google Scholar. Randomised controlled trials (RCTs) comparing pain outcomes in children receiving honey in addition to standard treatments versus those receiving standard treatments alone were included. Pain intensity was measured with the VAS tool. Meta‐analysis was performed using STATA version 14 software. Also, risk of bias and certainty of evidence were evaluated.ResultsOut of 537 articles, seven studies (n = 710) with RCT design met the inclusion criteria. The average duration for measuring pain intensity was 7.37 days. Pooled effect size showed a statistically significant reduction in pain intensity in the honey intervention group compared to the control group (WMD: −0.90, 95% CI [−1.32, −0.48], p < 0.001, I2: 92.5%; certainty of evidence: low). Also, the results demonstrated that honey significantly decreased the average time required for pain relief and analgesic consumption in the intervention group compared to the control group. One study was deemed low risk of bias, four studies were of intermediate quality and two studies were evaluated as high.ConclusionWhile honey shows promise in reducing post‐tonsillectomy pain, cautious use is advised due to the limited quality of evidence. More robust RCTs are needed to address biases and reinforce confidence in the findings.
Predicting Sarcopenia and Frailty Risk in Patients Post Heart Transplantation
Authors: Sentandreu‐Mañó Trinidad , Marques‐Sule Elena , Almenar‐Bonet Luis , Tomás José M. , Hansen Dominique , Deka Pallav , López‐Vilella Raquel , Klompstra Leonie , Machado Felipe V. C. 
Published: December 2024

ABSTRACTIntroductionCurrently, there is little evidence on the prevalence and factors associated with sarcopenia risk or frailty risk in patients post heart transplantation (HTx). The objective of this study was to analyze the influence of sociodemographic, lifestyle, physical, and psychological factors on sarcopenia and frailty risk in patients post‐HTx.Methods133 patients post‐HTx (59.4% men, mean age 56.5 ± 12.7 years) participated in this cross‐sectional study. The main outcomes were sarcopenia and frailty risk, and potential related predictors were comorbidities, time from transplantation, body mass index, sociodemographic factors, musculoskeletal pain, functional capacity, kinesiophobia, sleep problems, depression, physical activity, and diet quality. Multiple regression models were performed with all predictors, including polynomial regressions for predictors with a nonlinear relationship.ResultsThe predictor variables explained 73.93% of frailty's variance. Functional capacity (with a nonlinear relationship) and diet quality were significant predictors of frailty risk, while diabetes and physical activity were marginally significant. In addition, the predictors explained 73.52% of sarcopenia's variance. Diabetes, functional capacity (with a nonlinear relationship), and kinesiophobia were significant predictors of sarcopenia risk, while pain intensity and diet quality were marginally significant.ConclusionMultivariate analysis conducted on patients post‐HTx revealed that functional capacity was associated with both sarcopenia and frailty risk. Additionally, diet quality was a predictive factor of frailty, while diabetes and kinesiophobia were predictors of sarcopenia. These findings emphasize the importance of proper management to prevent frailty and sarcopenia, which share common associated factors.
With big data comes big responsibility: Strategies for utilizing aggregated, standardized, de‐identified electronic health record data for research
Authors: Olaker Veronica R. , Fry Sarah , Terebuh Pauline , Davis Pamela B. , Tisch Daniel J. , Xu Rong , Miller Margaret G. , Dorney Ian , Palchuk Matvey B. , Kaelber David C. 
Published: December 2024

AbstractElectronic health records (EHRs), though they are maintained and utilized for clinical and billing purposes, may provide a wealth of information for research. Currently, sources are available that offer insight into the health histories of well over a quarter of a billion people. Their use, however, is fraught with hazards, including introduction or reinforcement of biases, clarity of disease definitions, protection of patient privacy, definitions of covariates or confounders, accuracy of medication usage compared with prescriptions, the need to introduce other data sources such as vaccination or death records and the ensuing potential for inaccuracy, duplicative records, and understanding and interpreting the outcomes of data queries. On the other hand, the possibility of study of rare disorders or the ability to link apparently disparate events are extremely valuable. Strategies for avoiding the worst pitfalls and hewing to conservative interpretations are essential. This article summarizes many of the approaches that have been used to avoid the most common pitfalls and extract the maximum information from aggregated, standardized, and de‐identified EHR data. This article describes 26 topics broken into three major areas: (1) 14 topics related to design issues for observational study using EHR data, (2) 7 topics related to analysis issues when analyzing EHR data, and (3) 5 topics related to reporting studies using EHR data.
The Ontogeny of Attitudes Toward Migrants
Authors: Santhanagopalan Radhika , Hok Hannah , Shaw Alex , Kinzler Katherine D. 
Published: December 2024

ABSTRACTImmigration is among the most pressing issues of our time. Important questions concern the psychological mechanisms that contribute to attitudes about immigration. Whereas much is known about adults’ immigration attitudes, the developmental antecedents of these attitudes are not well understood. Across three studies (N = 616), we examined US children's attitudes toward migrants by introducing them to two novel groups of people: one native to an island and the other migrants to the island. The migrants varied by (1) Migrant Status: migrants came from a resource‐poor island (fleers) or a resource‐rich island (pursuers); and (2) Acculturation Style: migrants assimilated to the native culture (assimilated) or retained their original cultural identity (separated). We studied a range of children's immigration attitudes: children's preferences, resource allocations, and perceptions of solidarity between groups (Experiment 1), children's conferral of voting power (Experiment 2a) and political representation (Experiment 2b), and children's beliefs about political representation when an equal government was not possible (Experiment 3). Overall, children showed a bias toward natives, but the degree of their bias depended on the type of migrant they were evaluating. Children generally favored Pursuers over Fleers, and Assimilated migrants over Separated migrants. In some cases, the intersection of these factors mattered: children expressed a specific preference for Separated Pursuers and a specific penalization of Separated Fleers. These studies reveal the early developmental roots of immigration attitudes, particularly as they relate to political power and the intersecting forces of migrant status and acculturation.
Intentionality and Congruence Cues Shape Young Children's Perceptions of Identity‐Based Group Membership
Authors: Straka Brenda C. , Stanaland Adam , Gaither Sarah E. 
Published: December 2024

ABSTRACTAs young as 3 years old, children rely on a mutual intentionality framework to confer group membership—that is, agreement between a joiner (“I want to be in your group”) and group (“We want you to be in our group”). Here, we tested whether children apply this cognitive framework in the context of identity‐based groups, specifically gender and race. In Study 1 (preregistered), we asked a large sample of 3–8‐year‐olds (N = 448; 224 girls) whether a novel joiner character (girl, boy) could join a group (girls, boys) based on joiner‐group intentions (non‐mutual, mutual) and joiner‐group gender congruence (incongruent [e.g., girl‐to‐boys], congruent [e.g., girl‐to‐girls]). Study 2 (preregistered; N = 433; 208 minoritized race) followed the same structure as Study 1 but instead varied the race of the joiner (Black, White) and group (Black, White). In both studies, participants as young as 3 years old relied on a mutual intentionality framework to confer group membership. This effect strengthened with age, replicating past work and newly showing that children rely on mutual intentions in the context of identity‐based groups. An exploratory integrative data analysis (IDA) comparing across studies revealed that participants additionally relied on joiner‐group gender congruence to confer group membership as young as 3 years old (Study 1) but did not rely on joiner‐group racial congruence until 5 years old (Study 2). It appears, then, that young children's determination of group membership is influenced by interactive cognitive processes that incorporate others’ mental processes (intentions) and their emerging understanding of the social world (identity‐based group boundaries).
Exploring the Interplay Between Teachers' Emotions, Personal Traits, Environmental Factors and Psychological Well‐Being
Authors: Tong Qin 
Published: December 2024

ABSTRACTElevated stress levels among teachers are linked to both physical and mental health issues, which in turn affect their job performance. In addition, Teachers' ability to regulate emotions influences their instructional effectiveness and well‐being. Moreover, psychological well‐being is crucial for teachers' satisfaction and success, influenced by factors like burnout and personality traits and external circumstances impact teachers' stress levels and job performance, affecting their professional trajectory. Understanding these dynamics holistically is essential for fostering teacher well‐being and enhancing their effectiveness in the classroom; therefore, this study explores the intricate connections between various factors influencing teachers' professional success. To collect the data, the researchers used four questionnaires: environmental factor, Big Five personality traits, teachers' emotion and psychological well‐being questionnaires. Rigorous SEM analysis was employed to discern the direct and indirect influences of teachers' emotions, teachers' personal traits and environmental factors on teachers' psychological well‐being and their professional success. The findings revel that teachers' emotions, teachers' personal traits and environmental factors significantly predict teachers' psychological well‐being and their professional success. The study suggests that incorporating emotional regulation training into professional development can equip teachers with skills to navigate challenging situations, thereby enhancing their well‐being and effectiveness and establishing work environments that recognise and support and address the emotional needs of teachers can foster a positive atmosphere conducive to both well‐being and professional growth.
Mortality in Haemophilia Patients in India: A National Cohort Study
Authors: Shetty Shrimati , Ross Cecil , John M. Joseph , Kshirsagar Shrinath , Kulkarni Nimish , Pavitra D. S. , Sarwan Diksha , Misha P. K. , Paul Antony , More Apurva , Kaunchale Nazish , D'silva Magdalene , Masurkar Shrushti , Kharat Shruti , Patil Kranti , Patel Shalaka , Mehendale Priti , Sarvaiya Prachi , Rangarajan Savita 
Published: December 2024

ABSTRACTIntroductionMortality and morbidity in persons with haemophilia (PWH) have decreased due to improved diagnosis and treatment along with comprehensive population outreach efforts, but the impact is not uniform in different countries.AimThe study aims to assess all‐cause and intracranial haemorrhage (ICH)‐specific mortality of PWH in India.MethodsThis is a retrospective, observational, multi‐centric cohort study of 1020 haemophilia patients from three centres in India. The mortality data in the family was collected from personal interviews, and subsequently confirmed with the corresponding haemophilia treatment centres (HTCs). The demographic and clinical data, along with other comorbidities, were collected from the medical records.ResultsAmong 170 reported deaths, 73 (42.9%) were caused by ICH, and 44 (25.9%) resulted from accidents or trauma. Gastrointestinal (GI) bleeding was the third most common cause of death, accounting for 27 cases (15.9%). The average and median ages at death were 27.7 and 26 years, respectively. None of the deceased cases were receiving any prophylactic or immune tolerance induction (ITI) therapy, and all had severe haemophilia. In addition, the prevalence of inhibitors and hypertension was significantly higher in deceased cases compared to that in the general haemophilia population (p < 0.05).ConclusionSeverity of haemophilia, episodic treatment, hypertension and inhibitors showed significant association with mortality. ICH continues to be the leading cause of death among haemophilia patients in the country. This underscores the challenges in managing haemophilia and the need for improved treatment strategies to increase the life expectancy of PWH.
Low‐Dose Emicizumab Versus Low‐/Intermediate‐Dose Factor VIII Secondary Prophylaxis for Noninhibitor Haemophilia A Patients With Severe Bleeding Phenotype
Authors: Kessakorn Nuchanun , Gosriwatana Itsaraet , Sasipong Nuttarak , Srichumpuang Chonlatis , Moonla Chatphatai , Sosothikul Darintr 
Published: December 2024

ABSTRACTBackgroundSubcutaneous emicizumab, a factor VIII (FVIII)‐mimicking bispecific monoclonal antibody, can effectively prevent bleeds in haemophilia A (HA) patients with/without inhibitors; however, its standard‐dose regimens are financially burdensome. Low‐dose emicizumab prophylaxis may alternatively be applied to noninhibitor HA patients in resource‐limited settings.MethodsDuring 2023, Thai patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype (historical annualized bleeding rate [ABR] >5 bleeds/year before regular FVIII prophylaxis) who received low‐/intermediate‐dose FVIII secondary prophylaxis ≥8 months were enrolled. After the 4‐day washout period, low‐dose emicizumab prophylaxis (2.0–2.5 mg/kg every fortnight for two loading doses, then every 4 weeks) was implemented for 8 months. Pre‐/post‐emicizumab ABR, annualized joint bleeding rates (AJBR), haemophilia joint health scores (HJHS) and haemophilia‐specific quality‐of‐life (QoL) scores were analysed. Emicizumab plasma levels on modified one‐stage FVIII assays were also monitored.ResultsIn 15 subjects, ABR (median of differences, −2 bleeds/year; interquartile range, −3 to 0; p = 0.002), but not AJBR (p = 0.07), were reduced after switching to low‐dose emicizumab prophylaxis, although the pre‐dose emicizumab plasma levels at the steady state, achieved since week 12, were modest (median monthly level, 8.4 µg/mL; interquartile range, 4.3–10.4). Concurrently, HJHS (p = 0.008) and QoL score (p < 0.001) were decreased, and 46.7% had zero bleeds while receiving low‐dose emicizumab.ConclusionsLow‐dose emicizumab, compared to low‐/intermediate‐dose FVIII secondary prophylaxis, meaningfully improves bleeding prevention, joint health and QoL in patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype. This regimen potentially helps address previously unmet needs in HA care among low‐to‐middle‐income countries.Trial RegistrationClinicalTrials.gov identifier NCT06155955.
The Chronic Headache Self‐Efficacy Scale: Development and assessment of measurement properties
Authors: Ginoza Lori M. , Sigman Erica , Michener Lori A. , Straub Rachel K. , Sahai‐Srivastava Soma , Pozzi Federico 
Published: December 2024

AbstractObjectiveTo develop and assess the psychometrics of the Chronic Headache Self‐Efficacy Scale (CHASE).BackgroundExisting scales assess self‐efficacy in coping strategies and management of symptoms and triggers but do not measure other important self‐efficacy domains, such as performing daily activities and socializing in patients with chronic daily headache (CDH).MethodsThe study had two phases: (i) Development of the 14‐item CHASE, with items derived from patients with CDH and a multidisciplinary healthcare team; (ii) longitudinal observational study for psychometric evaluation. Participants with CDH (N = 79) completed the CHASE, Headache Management Self‐Efficacy Scale (HMSE), six‐item Headache Impact Test‐6 (HIT‐6), and 12‐item Short Form Health Survey (SF‐12) at baseline, 24–72 h after baseline, and 12 weeks after baseline. The Global Rating of Change (GROC) assessed perceived change in symptoms. We assessed internal consistency, day‐to‐day reliability, convergent and known group discriminant validity, dimensionality, and responsiveness via minimal clinical important difference (MCID).ResultsFor day‐to‐day reliability, the CHASE intraclass correlation coefficient was 0.68 (95% confidence interval 0.49–0.81), with standard error of measurement and minimal detectable change of 10.3% and 24%, respectively. The CHASE had two independent factors (total R2 = 54.5%) that can be combined into a single score (Cronbach's alpha internal consistency 0.88). For convergent validity, the CHASE score was related to the HIT‐6, HMSE, and SF‐12 (R2: 0.17–0.29, all p < 0.001). For known group discriminant validity, individuals with an active headache had a lower CHASE score than those without (mean [standard deviation] 47.7 [17.3]% vs. 57.2 [19.8]%, p < 0.001). Classification and regression tree analysis showed the MCID for meaningful positive symptom change on the GROC was a CHASE change of >8% or CHASE change of 8% with baseline CHASE >67%.ConclusionThe CHASE is a reliable and valid questionnaire for assessing self‐efficacy in performing daily activities, socializing, managing headache symptoms and triggers, and guiding treatment plans for patients with CDH.
Expression of claudin‐18.2 in cholangiocarcinoma: a comprehensive immunohistochemical analysis from a German tertiary centre
Authors: Kinzler Maximilian N , Gretser Steffen , Schulze Falko , Bankov Katrin , Abedin Nada , Bechstein Wolf O , Finkelmeier Fabian , Zeuzem Stefan , Reis Henning , Wild Peter J. , Walter Dirk 
Published: December 2024

AimsAnti‐claudin‐18.2 (CLDN18.2) therapy was recently approved for the treatment of gastric or gastro‐oesophageal junction adenocarcinoma. The aim of the present study was to investigate the expression of CLDN18.2 in cholangiocarcinoma (CCA) to determine whether there is a subgroup of patients who might also benefit from anti‐CLDN18.2 therapy.Methods and resultsA tissue microarray (TMA) cohort of all CCA patients who underwent surgical resection with curative intent between August 2005 and December 2021 at University Hospital Frankfurt were immunohistochemically evaluated using the VENTANA® CLDN18 (43‐14A) antibody. Tumour positivity for CLDN18.2 was determined as follows: ≥ 75% of tumour cells with moderate‐to‐strong CLDN18 membranous staining. In total, 160 patients with surgically resected CCA were suitable for immunohistochemistry (IHC) analysis. Of the patients, 13.1% (n = 21) showed moderate to strong membranous staining of VENTANA® CLDN18 antibody, while 86.9% (n = 139) were negative. Subtype analysis revealed strong differences in CLDN18 expression. Positive staining of CLDN18 could be observed in 26.5% (n = nine of 34) and 7.4% (n = seven of 95) of the perihilar (pCCA) and intrahepatic (iCCA) subgroup, respectively. CCA patients with CLDN18 expression had a more frequently intraoperative finding of distant metastasis (P = 0.002), lymph node metastasis (P = 0.008) and positive perineural invasion (Pn1) status (P = 0.022).ConclusionsThe present study suggests that a subset of patients with CCA exhibited a marked expression of CLDN18.2. These findings underline the need to perform a clinical study evaluating the efficacy of anti‐CLDN18.2 therapy in patients suffering from CCA.
Development of cordierite‐based low‐expansion porcelain tiles with application potential in an underfloor heating system
Authors: Luo Ting , Li Ping , Dong Weixia , Zeng Qiang , Yu Xiaoling , Gu Xingyong , Dong Gang 
Published: December 2024

AbstractThe high coefficients of thermal expansion (CTEs; α) of common porcelain tiles result in deformation, cracking and even breakage after prolonged utilization in an underfloor heating system. Cordierite‐based porcelain tiles with low α values have good application potential in underfloor heating systems. Herein, environmentally friendly and low‐cost cordierite‐based porcelain tiles made with desert sand were presented. The bulk density, linear shrinkage, water absorption, CTE, and modulus of rupture were determined to investigate the sintering stage of this desert sand‐based low‐expansion porcelain tiles. Powder X‐ray diffraction, scanning electron microscopy, and energy dispersive spectroscopy analyses were used to characterize the phase changes and microstructures of the materials. The results revealed that mass ratio of SiO2 to Al2O3 (m[SiO2/Al2O3]), mass ratio of MgO to Al2O3 (m[MgO/Al2O3]), and sintering temperature jointly affected the CTEs of the porcelain tiles. Moreover, the sintering temperature significantly impacted the quantities and morphologies of the cordierite crystals. An increase in the number of columnar‐like cordierite crystals during production resulted in a decreased CTE. The results of this study present an effective technique for preparing low‐CTE porcelain tiles from natural waste materials. These desert sand‐based tiles could be widely applied in underfloor heating systems.