bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry
Authors: Bogucki Aleksander , John Ivo , Zinkiewicz Łukasz , Jachura Michał , Jaworski Damian , Suwała Karolina , Chrost Hugo , Wlodarski Michal , Kałużny Jakub , Campbell Doug , Bakken Paul , Pandya Shawna , Chrapkiewicz Radosław , Manohar Sanjay G. 
Published: April 2024

IntroductionThe pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations.Methods and resultsWe assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (&lt;5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0–5 (0, non-reactive pupil; 0–3, abnormal/“sluggish” response; 3–5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude.DiscussionThis is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.
The dilemma of neuroprotection trials in times of successful endovascular recanalization
Authors: Schmidt-Pogoda Antje , Kaesmacher Johannes , Bonberg Nadine , Werring Nils , Strecker Jan-Kolja , Koecke Mailin Hannah Marie , Beuker Carolin , Gralla Jan , Meier Raphael , Wiendl Heinz , Minnerup Heike , Fischer Urs , Minnerup Jens 
Published: April 2024

BackgroundThe “translational roadblock” between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution.MethodsTo verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later.ResultsOur preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%.ConclusionOur study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.
Elevated gut microbiota metabolite bile acids confer protective effects on clinical prognosis in ischemic stroke patients
Authors: Wang Zhaobin , Li Jing , Xu Yingxin , Liu Ye , Zhang Zhe , Xu Qin , Lin Jinxi , Jiang Yong , Wang Yongjun , Jing Jing , Wang Anxin , Meng Xia 
Published: April 2024

BackgroundThere is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored.MethodsPatients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines.ResultsData for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55–0.78; p &lt; 0.001) and 0.66 (95% CI 0.55–0.78, p &lt; 0.001). Each standard deviation increase in the TBA level reduced the risks of disability and poor functioning outcomes by 10% (adjusted ORs 0.9 [95% CI 0.83–0.98; p = 0.01] and 0.9 [95% CI 0.83–0.97; p &lt; 0.001], respectively). This association remained similar at the 1-year follow-up. After stratification by TOAST subtype, the risk of disability or a poor functional outcome in patients with the large-artery atherosclerosis or “other” subtype was significantly lower in the highest quartile than in the lowest quartile (p &lt; 0.05).ConclusionSerum TBA is an independent risk factor for disability and poor functional outcomes after AIS or TIA, and exerts a protective effects on brain.
Factors associated with stunting in under-five children with environmental enteropathy in slum areas of Jimma town, Ethiopia
Authors: Regassa Rediet , Belachew Tefera , Duguma Markos , Tamiru Dessalegn 
Published: April 2024

IntroductionStunting is a major public health issue with a significant influence on the health and development of children in low-income countries, where it affects up to 32% of children. Nutritional intake is impacted by alterations in intestinal permeability and underlying chronic inflammation, which hinder children’s normal linear growth. Environmental enteropathy is a poorly understood condition with chronic intestinal inflammation. The purpose of this study was to identify the magnitude of stunting, change in growth, and factors associated with stunting and change in height for the age Z-score of children with an elevated lactulose-to-mannitol ratio.MethodsAn observational follow-up study was conducted to follow children with an elevated lactulose-to-mannitol ratio for changes in their linear growth. A lactulose–mannitol test was performed to identify children with elevated lactulose-to-mannitol ratios, indicative of environmental enteropathy. After a 1-year follow-up, anthropometry was repeated to assess their linear growth. A multivariable logistic regression analysis was performed to identify the independent predictors for stunting in children with elevated lactulose-to-mannitol ratios. All tests were two-sided, and a p-value of &lt;0.05 was considered significant.ResultsThe prevalence of stunting in children with an elevated L:M at baseline and end line was found to be 72.4% (95% CI: 60.3, 84.5) and 78.4% (95% CI: 66.7, 90.2), respectively. In a multivariate analysis, a low dietary diversity score (&lt;4 food groups), presence of flies and insects in the toilet area, poor handwashing practices during a critical time, and MUAC z &lt; −2 were significantly associated with stunting. Flies and insects in the toilet area and unsafe disposal of feces were significantly associated with changes in HAZ in children with elevated lactulose-to-mannitol ratios, an indicator of environmental enteropathy.ConclusionMost of the children with an elevated lactulose-to-mannitol ratio in the study population were stunted, and no significant change in their linear growth was observed after 1-year follow-up. Therefore, further investigation and urgent intervention are needed to prevent environmental enteropathy and stunting among under-five children in this community who are exposed to very poor sanitary conditions and other risk factors for malnutrition.
Clinical efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapy for relapsed/refractory multiple myeloma: a systematic review and meta-analysis
Authors: Xu Han , Guan Chaoyang , Xu Peipei , Zhou Dongming , Xu Yong , Chen Bing , Bai Hua 
Published: April 2024

BackgroundThe low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety.MethodsWe collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002.ResultsOur meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11).ConclusionsAs a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.
Sunitinib for adenocarcinoma of the rete testis: a case report
Authors: Li Kezhen , Chen Di , He Mingdong , Yu Jun , Mi Hua 
Published: April 2024

BackgroundAdenocarcinoma of the rete testis (AORT) is an extremely rare and aggressive tumor with a poor prognosis. Its etiology and pathological characteristics have not been extensively studied, making accurate diagnosis and appropriate management challenging. AORT, an invasive testicular tumor with a mortality rate of 46%, treatment typically involves radical orchiectomy, retroperitoneal pelvic lymph node dissection (RPLND), adjuvant chemotherapy, and/or ongoing monitoring, but the response to conventional radiation and chemotherapy is limited. At present, no effective targeted therapy for AORT has been found.Case descriptionIn this case report, we present the clinical scenario of a 50-year-old male patient initially diagnosed with a right testicular hydrocele, who subsequently underwent eversion of the parietal tunica vaginalis. Postoperative pathological analysis revealed metastatic clear cell renal cell carcinoma (ccRCC). PET/CT demonstrated findings suggestive of left renal upper pole carcinoma with involvement of the right scrotum, para-aortic region, bilateral iliac vessels, bilateral inguinal region, and multiple metastases. Sunitinib, a tyrosine kinase inhibitor, is commonly employed in the treatment of ccRCC. The patient underwent treatment with sunitinib for a duration of 20 months, resulting in the inactivation of multiple metastases. Following this, a radical orchiectomy was performed, and the postoperative pathology confirmed the presence of AORT. This article provides a comprehensive account of the patient's medical history, diagnostic process, treatment modalities, and subsequent follow-up observations.ConclusionsThis case report highlights the successful use of targeted therapy with sunitinib in a patient with AORT. The patient showed a positive response to targeted therapy. This study not only provides a novel foundation for the treatment of AORT, but also offers valuable insights for future treatment strategies in managing this particular form of testicular cancer.
Case report: Salivary duct carcinoma in a patient with a germline CDH1 pathogenic variant - expanding the spectrum of hereditary cancer predisposition syndromes
Authors: Desai Nidhi , Racila Emilian , Fujioka Naomi , Gupta Arjun , Antonarakis Emmanuel S. 
Published: April 2024

IntroductionRecently, an entity known as salivary duct carcinoma with rhabdoid features (SDC-RF) has been associated with somatic CDH1 mutations. Here we present the first known case report of conventional SDC occurring in the setting of a germline CDH1 pathogenic variant accompanied by a somatic loss of heterozygosity at the CDH1 locus.Case discussionA 67-year-old man presented with chest and back pain and was found to have osteolytic lesions in the sternum and lumbar spine. Vertebral bone biopsies were positive for metastatic carcinoma of unknown primary. A molecular profiling assay consisting of both whole-exome next-generation sequencing (NGS) as well as immunohistochemistry (IHC) for select clinically-relevant proteins performed on the bone biopsy suggested a triple-negative (ER/PR/ERBB2 negative, by IHC), androgen receptor (AR IHC) positive tumor profile. Additionally, the assay uncovered a coding mutation in the CDH1 gene (c.1792C&gt;T, p.R598*) with genomic loss of the second CDH1 allele. Germline testing returned positive for a heterozygous CDH1 pathogenic variant. PET-CT revealed a tumor in the neck suggestive of the primary malignancy consistent with that of salivary gland origin. The patient was initially treated with carboplatin and paclitaxel, then pembrolizumab, and finally with AR-directed therapy using leuprolide and enzalutamide. These treatments were not successful, and the patient eventually succumbed to his disease.ConclusionMolecular testing revealed that our patient had bi-allelic inactivation of the CDH1 gene. We believe our patient developed a somatic mutation in addition to his preexisting germline CDH1 mutation that ultimately predisposed him to SDC. While previous studies have found somatic CDH1 pathogenic variants in SDC-RF, our patient was found to have a germline CDH1 pathogenic variant in the setting of conventional SDC, without rhabdoid features. This case provokes questions regarding tumor genetics and molecular profiling of SDC in patients with germline CDH1 pathogenic variants. Moreover, this case supports the notion that SDC may be the salivary counterpart of other malignancies associated with germline CDH1 pathogenic variants and may possibly expand the spectrum of tumors that arise in this familial cancer-predisposition syndrome.
Statins use amidst the pandemic: prescribing, dispensing, adherence, persistence, and correlation with COVID-19 statistics in nationwide real-world data from Poland
Authors: Kardas Przemysław , Kwiatek Angelika , Włodarczyk Piotr , Urbański Filip , Ciabiada-Bryła Beata 
Published: April 2024

BackgroundAdherence to medications presents a significant challenge in healthcare. Statins, used in primary and secondary prevention of cardiovascular disease, are of particular importance for public health. The outbreak of the COVID-19 pandemic resulted in additional healthcare system-related barriers impeding the execution of therapies. This study aimed to assess the use of as well as adherence and persistence to statins in a national cohort of 38 million of Polish citizens during pandemic.MethodsA retrospective analysis of prescription and dispensation data for all statins users from the national payer organization covering the years 2020–2022 was conducted. Medication adherence was assessed using the Medication Possession Ratio, for persistence the 30-day cut-off was accepted. National data on COVID-19 cases and COVID-19 related deaths were obtained from ECDC.ResultsThe analysis identified 7,189,716 Polish citizens (approximately 19% of Polish population) who were dispensed at least 1 pack of statins within the study period. Over that time, there was a continuous significant increasing trend in prescribing and dispensing of statins. Despite a total increase of 18.9% in the number of prescribed tablets, the percentage of tablets dispensed remained similar, averaging 86%. Overall percentage of adherent patients was 48.2%. For a random sample of 100,000 patients, the mean period of continuous therapy in 2022 was 6.2+/- 5.3 months. During the lockdown period, the mean number of prescribed and dispensed tablets was lower by 6.8% and 5.9%, respectively (p &lt; 0.05). However, fluctuations in the number of COVID-19 cases or COVID-19-related deaths per week had no major impact on the prescribing and dispensing of statins.ConclusionOver the time of pandemic, there was a continuous increase in the number of statin tablets prescribed and dispensed in Poland. This suggests that, despite the potential limitations posed by COVID-19, access to statins remained easy, which may be attributed to the mass-scale implementation of the national e-prescription system. However, it is crucial to realise that approximately 1/7 of prescribed statin doses were never dispensed, and the overall levels of adherence and persistence were low. This underscores the necessity for concerted efforts to change this scenario in Poland.
Feasibility of the application of frequency modulated continuous wave radar trigger technique in abdominal magnetic resonance imaging
Authors: Song Qingling , He Yongquan , Chen Lihua , Xia Xinyuan , Wang Nan , Song Qingwei , Liu Ailian 
Published: April 2024

Objective: To evaluate and compare the image quality of T2-weighted abdominal scans using a respiratory belt trigger (RBT) and frequency-modulated continuous wave (FMCW)-trigger (FT) techniques and to explore the feasibility of FT in abdominal magnetic resonance imaging (MRI).Methods: The study prospectively included 28 subjects, each undergoing abdominal scans with both RBT and FT. The analysis focused on 64 inconsistent trigger segments from the respiratory curves triggered by RBT and FMCW. Parameters such as inconsistent trigger type (ITT), number of inconsistent trigger points (ITPs), ratio of ITP (ITR), and single-segment ITR (SITR) were derived from these curves. Image quality was evaluated by two observers using subjective scoring, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The assessments classified image quality as either “good” or “poor.” Consistency in image quality assessment between observers was determined using the kappa test and intraclass correlation coefficient (ICC). The chi-square test, Student’s t-test, and the Mann–Whitney U test were employed to compare the categorical and continuous variables between the RBT and FT groups.Results: The observers showed a high level of agreement in image quality assessment. There were no significant differences in ITR, SITR, acquisition time, SNR, and CNR between the RBT and FT groups (all p &gt; 0.05). Both subjective and objective evaluations indicated no notable difference in image quality between the two groups (p &gt; 0.05).Conclusion: The FMCW trigger technique is a viable alternative to the traditional respiratory belt trigger in scenarios of relatively stable breathing. It offers potential benefits, such as reducing operational demands on technicians and improving MRI workflow efficiency.
Effects of musical expertise on line section and line extension
Authors: Pei Yilai , Xu Zhiyuan , He Yibo , Liu Xinxin , Bai Yuxuan , Kwok Sze Chai , Li Xiaonuo , Wang Zhaoxin 
Published: April 2024

BackgroundThis study investigated whether music training led to better length estimation and/or rightward bias by comparing the performance of musicians (pianists) and non-musicians on performance of line sections and line extensions.MethodsOne hundred and sixteen participants, among them 62 musicians and 54 non-musicians, participated in the present study, completed line section and line extension task under three conditions: 1/2, 1/3 and 2/3.ResultsThe mixed repeated measures ANOVA analysis revealed a significant group × condition interaction, that the musicians were more accurate than non-musicians in all the line section tasks and showed no obvious pseudoneglect, while their overall performance on the line extension tasks was comparable to the non-musicians, and only performed more accurately in the 1/2 line extension condition.ConclusionThese findings indicated that there was a dissociation between the effects of music training on line section and line extension. This dissociation does not support the view that music training has a general beneficial effect on line estimation, and provides insight into a potentially important limit on the effects of music training on spatial cognition.
Exploring the potential of ChatGPT for foreign language education at the university level
Authors: Klimova Blanka , Pikhart Marcel , Al-Obaydi Liqaa Habeb 
Published: April 2024

IntroductionThe purpose of this study is to explore students’ attitudes and perceived usefulness of using ChatGPT for learning a foreign language to reveal how this new trend tool affects its end-users.MethodsThe authors conducted qualitative research by using a questionnaire survey based on hands-on experience by university students.ResultsThe findings reveal that students are fascinated, satisfied, and stimulated to use this technology despite some of their reservations and potential threats. The authors of this study also list pedagogical implications, including specific activities, while using ChatGPT.DiscussionAlthough ChatGPT can be very beneficial for teachers and help them in their preparation, it sets a challenging task for them to change the existing teaching approaches and assessments to boost students’ cognitive, creative, and critical thinking skills. In addition, both teachers and students will have to upskill their competencies to handle the current advancements in AI technology, such as ChatGPT.