bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proof-of-Concept Study of Sequential Treatment with the HDAC Inhibitor Vorinostat following BRAF and MEK Inhibitors in BRAF
V600-Mutated Melanoma
Authors: Embaby Alaa , Huijberts Sanne C.F.A. , Wang Liqin , Leite de Oliveira Rodrigo , Rosing Hilde , Nuijen Bastiaan , Sanders Joyce , Hofland Ingrid , van Steenis Charlaine , Kluin Roelof J.C. , Lieftink Cor , Smith Christopher G. , Blank Christian U. , van Thienen Johannes V. , Haanen John B.A.G. , Steeghs Neeltje , Opdam Frans L. , Beijnen Jos H. , Huitema Alwin D.R. , Bernards Rene , Schellens Jan H.M. , Wilgenhof Sofie 
Published: May 2024

Abstract

Purpose:
The development of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600-mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of resistant tumor cells. We aimed to assess the antitumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600-mutated melanoma who progressed after initial response to BRAFi/MEKi.

Patients and Methods:
Patients with BRAFi/MEKi-resistant BRAFV600-mutated melanoma were treated with vorinostat 360 mg once daily for 14 days followed by BRAFi/MEKi. The primary endpoint was an objective response rate of progressive lesions of at least 30% according to Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included progression-free survival, overall survival, safety, pharmacokinetics of vorinostat, and translational molecular analyses using ctDNA and tumor biopsies.

Results:
Of the 26 patients with progressive BRAFi/MEKi-resistant BRAFV600-mutated melanoma receiving treatment with vorinostat, 22 patients were evaluable for response. The objective response rate was 9%, with one complete response for 31.2 months and one partial response for 14.9 months. Median progression-free survival and overall survival were 1.4 and 5.4 months, respectively. Common adverse events were fatigue (23%) and nausea (19%). ctDNA analysis showed emerging secondary mutations in NRAS and MEK in eight patients at the time of BRAFi/MEKi resistance. Elimination of these mutations by vorinostat treatment was observed in three patients.

Conclusions:
Intermittent treatment with vorinostat in patients with BRAFi/MEKi-resistant BRAFV600-mutated melanoma is well tolerated. Although the primary endpoint of this study was not met, durable antitumor responses were observed in a minority of patients (9%).
IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity
Authors: Wei Jian , Mayberry Colleen L. , Lv Xiaoting , Hu Fangyan , Khan Taushif , Logan Natalie A. , Wilson John J. , Sears John D. , Chaussabel Damien , Chang Chih-Hao 
Published: May 2024

Abstract
Cytotoxic T lymphocytes (CTL) are pivotal in combating cancer, yet their efficacy is often hindered by the immunosuppressive tumor microenvironment, resulting in CTL exhaustion. This study investigates the role of interleukin-3 (IL3) in orchestrating antitumor immunity through CTL modulation. We found that intratumoral CTLs exhibited a progressive decline in IL3 production, which was correlated with impaired cytotoxic function. Augmenting IL3 supplementation, through intraperitoneal administration of recombinant IL3, IL3-expressing tumor cells, or IL3-engineered CD8+ T cells, conferred protection against tumor progression, concomitant with increased CTL activity. CTLs were critical for this therapeutic efficacy as IL3 demonstrated no impact on tumor growth in Rag1 knockout mice or following CD8+ T-cell depletion. Rather than acting directly, CTL-derived IL3 exerted its influence on basophils, concomitantly amplifying antitumor immunity within CTLs. Introducing IL3-activated basophils retarded tumor progression, whereas basophil depletion diminished the effectiveness of IL3 supplementation. Furthermore, IL3 prompted basophils to produce IL4, which subsequently elevated CTL IFNγ production and viability. Further, the importance of basophil-derived IL4 was evident from the absence of benefits of IL3 supplementation in IL4 knockout tumor-bearing mice. Overall, this research has unveiled a role for IL3-mediated CTL–basophil cross-talk in regulating antitumor immunity and suggests harnessing IL3 sustenance as a promising approach for optimizing and enhancing cancer immunotherapy.
See related Spotlight, p. 798
Assessment and Application of Digital Museum Visitors' Emotional Experience Based on Virtual Reality Technology and Emotion Recognition Algorithm
Authors: An Jun 
Published: May 2024

Abstract
Each person will have a different emotional experience for the same scene or exhibit, which reduces the accuracy of emotional recognition and leads to the complexity of the evaluation of visitors' emotional experience in digital museums. In order to improve the user experience of digital museums, the evaluation and optimization methods of visitors' emotional experience of digital museums based on virtual reality (VR) technology and emotion recognition algorithm are studied. A spectrogram is generated according to the voice sent by tourists when they visit the digital museum, which is based on the CSWNet_CRNN emotion recognition depth learning model input, which evaluates tourists' emotional experience results and draws their emotional responses to digital museums. The visual and auditory features of the digital museum scene with positive emotional experience are extracted, respectively. Using VR technology, the extracted features are applied to each link of the digital museum scene content design, optimizing the digital museum VR scene and improving the digital museum experience. The experiment shows that the tourist emotion recognition accuracy of this method is high, and the emotion recognition accuracy of 300 random tourists can reach 100%. In terms of generating new scenes, the feature extraction results of this scene are consistent with the feature estimation of positive emotions by ordinary people. The use of extracted features to optimize the digital museum scene has better realism and detail accuracy, which can be favored by most people and promotes the sustainable development of digital museums.
India’s Silent Struggle: A Scoping Review on Postpartum Depression in the Land of a Billion Mothers
Authors: Rajeev S. P.  , Nair Gokul M. , K. Krishna K. , Maria Chris 
Published: May 2024

Background: Postpartum emotional issues, including postpartum blues, postpartum psychosis, and postpartum depression (PPD), affect many mothers worldwide. The prevalence of postpartum blues ranges from 300 to 750 per 1,000 mothers, while postpartum psychosis has a prevalence of 0.89–2.6 cases per 1,000 births. PPD affects 100–150 new mothers per 1,000 births, and its prevalence can go above 25% globally. Depression in mothers can have long-lasting impacts on children and the next generation, affecting their growth, development, and relationships. However, the condition of PPD is frequently misdiagnosed, and women who suffer from it do not receive treatment. There is a lack of solid systematic evidence that looks at the overall burden of PPD and the risk factors that are associated with it in India. The awareness of PPD is critical in managing the symptoms and seeking professional support, and studies are needed to evaluate and assess the situation in India. Methodology: This study is a systematic literature review with a scoping review approach aimed at providing existing evidence on the awareness and prevalence of PPD in India. The search strategy for the electronic bibliographic search included a list of related terms and factors of awareness and prevalence of PPD. The search encompassed six prominent databases. The assessment tools used in studies from 2012 to 2023 study the factors using the Postpartum Depression Literacy Scale (PoDLiS) and the Edinburgh Postpartum Depression Scale, which measure the awareness and prevalence of PPD. Results: The study found a significantly low volume of studies conducted in India to determine the prevalence of PPD. The materials or studies accessible are hospital-based research with a minimal number of samples. The reported prevalence rate of postpartum depression (PPD) in India varies across different studies, ranging from 4% to 48.5%. Among mothers who gave birth either naturally or by cesarean section in a hospital setting, one study reported the lowest prevalence rate (4%). The prevalence of PPD among women in India is estimated to be 18% based on the average score across all research. A study that evaluated the moms in the community found that PPD was prevalent in new mothers at a rate of 21.5%. There are three studies, in particular, that focus on how aware people are of PPD. Two studies found that 54% of the family members of postpartum moms and women undergoing tertiary pediatric care are aware of PPD. Discussion: Many studies point to the lack of social support as a significant risk factor for mental health complications after delivery. History of depression, anxiety, adverse life events, partner abuse, low economic status, complications at childbirth, and a traumatic childbirth experience are some of the associated factors identified in the studies. Studies have also shown that women who undergo a cesarean section have a higher risk of developing PPD than those with a vaginal delivery.
Evaluation of an aPTT guided versus a multimodal heparin monitoring approach in patients on extra corporeal membrane oxygenation: A retrospective cohort study
Authors: Taha Diman , Drop Joppe G , Wildschut Enno D , De Hoog Matthijs , van Ommen C. Heleen , Reis Miranda Dinis Dos 
Published: May 2024

Introduction Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated. Methods This is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements. Results In total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9). Discussion The incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.
Feedback Loop Failure Modes in Medical Diagnosis: How Biases Can Emerge and Be Reinforced
Authors: Aikens Rachael C. , Chen Jonathan H. , Baiocchi Michael , Simard Julia F. 
Published: May 2024

Background Medical diagnosis in practice connects to research through continuous feedback loops: Studies of diagnosed cases shape our understanding of disease, which shapes future diagnostic practice. Without accounting for an imperfect and complex diagnostic process in which some cases are more likely to be diagnosed correctly (or diagnosed at all), the feedback loop can inadvertently exacerbate future diagnostic errors and biases. Framework A feedback loop failure occurs if misleading evidence about disease etiology encourages systematic errors that self-perpetuate, compromising future diagnoses and patient care. This article defines scenarios for feedback loop failure in medical diagnosis. Design Through simulated cases, we characterize how disease incidence, presentation, and risk factors can be misunderstood when observational data are summarized naive to biases arising from diagnostic error. A fourth simulation extends to a progressive disease. Results When severe cases of a disease are diagnosed more readily, less severe cases go undiagnosed, increasingly leading to underestimation of the prevalence and heterogeneity of the disease presentation. Observed differences in incidence and symptoms between demographic groups may be driven by differences in risk, presentation, the diagnostic process itself, or a combination of these. We suggested how perceptions about risk factors and representativeness may drive the likelihood of diagnosis. Differing diagnosis rates between patient groups can feed back to increasingly greater diagnostic errors and disparities in the timing of diagnosis and treatment. Conclusions A feedback loop between past data and future medical practice may seem obviously beneficial. However, under plausible scenarios, poorly implemented feedback loops can degrade care. Direct summaries from observational data based on diagnosed individuals may be misleading, especially concerning those symptoms and risk factors that influence the diagnostic process itself. Highlights Current evidence about a disease can (and should) influence the diagnostic process. A feedback loop failure may occur if biased “evidence” encourages diagnostic errors, leading to future errors in the evidence base. When diagnostic accuracy varies for mild versus severe cases or between demographic groups, incorrect conclusions about disease prevalence and presentation will result without specifically accounting for such variability. Use of demographic characteristics in the diagnostic process should be done with careful justification, in particular avoiding potential cognitive biases and overcorrection.
Stability of Willingness to Pay: Does Time and Treatment Allocation in a Randomized Controlled Trial Influence Willingness to Pay?
Authors: van der Pol Marjon , Watson Verity , Boyers Dwayne 
Published: May 2024

Background Willingness-to-pay (WTP) estimates are useful to policy makers only if they are generalizable beyond the moment when they are collected. To understand the “shelf life” of preference estimates, preference stability needs be tested over substantial periods of time. Methods We tested the stability of WTP for preventative dental care (scale and polish) using a payment-card contingent valuation question administered to 909 randomized controlled trial participants at 4 time points: baseline (prerandomization) and at annual intervals for 3 years. Trial participants were regular attenders at National Health Service dental practices. Participants were randomly offered different frequencies (intensities) of scale polish (no scale and polish, 1 scale and polish per year, 2 scale and polishes per year). We also examined whether treatment allocation to these different treatment intensities influenced the stability of WTP. Interval regression methods were used to test for changes in WTP over time while controlling for changes in 2 determinants of WTP. Individual-level changes were also examined as well as the WTP function over time. Results We found that at the aggregate level, mean WTP values were stable over time. The results were similar by trial arm. Individuals allocated to the arm with the highest scale and polish intensity (2 per year) had a slight increase in WTP toward the latter part of the trial. There was considerable variation at the individual level. The WTP function was stable over time. Conclusions The payment-card contingent valuation method can produce stable WTP values in health over time. Future research should explore the generalizability of these results in other populations, for less familiar health care services, and using alternative elicitation methods. Highlights Stated preferences are commonly used to value health care. Willingness-to-pay (WTP) estimates are useful only if they have a “shelf life.” Little is known about the stability of WTP for health care. We test the stability of WTP for dental care over 3 y. Our results show that the contingent valuation method can produce stable WTP values.
Neutrophils-derived Parameters as Cost-effective Inflammatory, Disease Activity Marker in Systemic Lupus Erythematosus (SLE) and Role in Prediction of Lupus Nephritis
Authors: Farheen Shaila , Sharma Seema , Rao Ram Nawal , Linghaiah Raghavendra , Aggarwal Amita 
Published: May 2024

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations and approximately 50% of the SLE patients develop lupus nephritis (LN), which increases the risk of renal failure, cardiovascular diseases and overall survival. Objectives: Evaluation of neutrophil-derived parameters (Neut-X, Neut-Y and Neut-Z) as an inflammatory, disease activity marker and as a predictor of nephritis in SLE patients. Material and Methods: In this cross-sectional study, 3 ml K3EDTA blood was taken from 110 SLE patients presented in Department of Clinical Immunology to evaluate neutrophil-derived parameters in Sysmex XT2000i haematology analyser and their correlation with other inflammatory biomarkers like, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as SLE disease activity index-2000 (SLEDAI-2K). 24-hours urine protein levels were also estimated as a marker of renal involvement. Records of renal biopsy were available in 73 SLE patients, who belonged to different morphologic classification of LN. Results: After performing bivariate Spearman correlation analysis (SPSS software, version 26.0), Neut-X (measures cytoplasmic granularity by side scattering) and Neut-Z (vector sum of Neut-X and Neut-Y) showed a significant positive correlation ( r > 0.200, P < .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r > 0.200, P < .05) with ESR and CRP. Receiver-operating characteristic curve analysis was used to evaluate diagnostic value of 24-hour urine protein and predictive values of neutrophil-derived parameters for renal involvement in SLE patients. Among neutrophil-derived parameters, Neut-X was found to be the best predictor of renal dysfunction with highest AUC of 0.710 (95% CI: 0.604-0.816; cut-off: 1344.50; sensitivity: 84.7%; specificity: 50%) followed by Neut-Z with AUC of 0.707 (95% CI: 0.600-0.813; cut-off: 1403.67; sensitivity: 87.5%; specificity: 50%). Conclusion: Our study shows that neutrophil-derived parameters may be used as novel cost-effective, non-invasive biomarker of disease activity as well as for predicting renal involvement in SLE patients.
Evaluating Oral Probiotic Supplements as Complementary Treatment in Advanced Lung Cancer Patients Receiving ICIs: A Prospective Real-World Study
Authors: Tong Liping , Wan Yuming , Shi Xiaoxiao , Liu Xianguo , Liu Zhe , Li Yuehua , Zhang Yan , Luo Deyun , Zhu Jiang 
Published: May 2024

Objective To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. Methods This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). Results A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. Conclusion Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.
Smoking Habits and Nicotine Dependence Among the General Lebanese Population Before and During Both the Economic Crisis and COVID-19 Pandemic
Authors: Haddad Nina Rossa , Aoun Charbel B. , Mghames Abdo , Saleh Mustafa , Chahine Mirna N. 
Published: May 2024

Objective Smoking habits have widely changed over time; however, they remain a well-known fashion that risks people’s health. In addition, nicotine addiction depends on the interplay between several factors. Our study aimed to understand the smoking habits and nicotine dependence in the Lebanese population before (September 2019) and during (June 2020) the economic crisis and COVID-19 pandemic. Methods This observational cross-sectional survey-based study included 1560 Lebanese individuals aged between 13 and 75 years old from June till October 2020. Data collection was performed through an electronic survey including patients’ demographics and validated instruments to assess addiction to nicotine (CAGE, Four C’s, Fagerström test, and Smoker’s profile scores). Results Out of 1560 participants, 794 (50.9%) were males. The mean age was 26.5 ± 11.69 years, and 67.8% were aged between 18 and 25 years old. We found that 865 (55.4%) participants were smokers. In addition, smoking cigarettes or vaping, significantly increased between September 2019 and June 2020. Our smoker group showed a high CAGE positivity ( P < .001), marked compulsion ( P < .001), and a considerable lack of self-control to surcease smoking ( P < .001). Furthermore, the nicotine dependence score (NDS) increased with age (B = .166) and decreased with higher educational levels (B = −.219). Conclusion During the economic crisis and the COVID-19 pandemic, the Lebanese population showed an increased prevalence of smoking, a high level of CAGE positivity, strong compulsion, and a significant lack of self-control when it came to quitting smoking. This strongly entails public health measures for smoking cessation through national awareness campaigns.