bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis
Authors: Shimizu Takashi , Inoue Eisuke , Ohkuma Ryotaro , Kobayashi Shinichi , Tsunoda Takuya , Wada Satoshi 
Published: November 2023

IntroductionCurrently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (≧50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data meta-analysis of PD-1 inhibitor treatments.MethodsWe conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses.ResultsFrom our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52–3.02)/PFS (HR = 1.42; CI: 0.61–3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab).ConclusionOur findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixed-point observations.
Treatment preferences of patients with relapsed or refractory multiple myeloma in the United States, United Kingdom, Italy, Germany, France, and Spain: results from a discrete choice experiment
Authors: Thomas Caitlin , Ailawadhi Sikander , Popat Rakesh , Kleinman David , Ross Melissa M. , Gorsh Boris , Mulnick Sarah , O’Neill Alicia , Paka Prani , Hanna Maya , Krucien Nicolas , Molinari Alexa , Gelhorn Heather L. , Perera Sue 
Published: November 2023

IntroductionNewer treatment options for relapsed/refractory multiple myeloma (RRMM) with efficacy and safety profiles that differ from traditional therapies have facilitated personalized management strategies to optimize patient outcomes. In the context of such personalized management, understanding how treatment characteristics influence patients’ preferences is essential. This study assessed patients’ preferences for RRMM treatment attributes and determined trade-offs between potential benefits, administration procedures, and adverse effects.MethodsPatients’ preferences were evaluated using a discrete choice experiment (DCE). Patients with RRMM who reported failing two lines of anti-myeloma treatment (immunomodulatory agent and a proteasome inhibitor [PI]) or ≥ 3 lines (including ≥1 PI, immunomodulatory agent, or anti-CD38 monoclonal antibody), were recruited across the US, UK, Italy, Germany, France, and Spain. DCE attributes and levels were identified using a targeted literature review, a review of clinical data for relevant RRMM treatments, qualitative patient interviews, and input from clinical and myeloma patient experts. The DCE was administered within an online survey from February–June 2022. Preference data were analyzed using an error-component logit model and willingness to make trade-offs for potential benefits, and relative attribute importance scores were calculated.ResultsOverall, 296 patients from the US (n = 100), UK (n = 49), Italy (n = 45), Germany (n = 43), France (n = 39), and Spain (n = 20) participated in the DCE. Mean (standard deviation) age was 63.8 (8.0) years, 84% had a caregiver, and patients had a median of 3 (range: 2–8) prior lines of therapy. Efficacy attributes most influenced patients’ preferences, with increasing overall response rate (25–85%) and overall survival (6 months to 2 years) contributing to ~50% of treatment decision-making. Administration procedures were also considered important to patients. Avoiding individual side effects was considered relatively less important, with patients willing to tolerate increases in side effects for gains in efficacy. Patient characteristics such as rate of disease progression, sociodemographics, or clinical characteristics also influenced treatment preferences.ConclusionPatients with RRMM were willing to tolerate increased risk of side effects for higher efficacy. Preferences and risk tolerance varied between patients, with preference patterns differing by certain patient characteristics. This highlights the importance of shared decision-making for optimal treatment selection and patient outcomes.
A blended learning approach for teaching thoracic radiology to medical students: a proof-of-concept study
Authors: Stoehr Fabian , Yang Yang , Müller Lukas , Gerstenmeier Phyllis , Pinto dos Santos Daniel , Dietz Pavel , Weimer Andreas , Ludwig Michael , Kloeckner Roman , Weimer Johannes Matthias 
Published: November 2023

IntroductionThe best way to impart knowledge to medical students is still unclear. Therefore, we designed a blended learning course in thoracic radiology including both “traditional” in-class time as well as online learning modules. The aims were (1) to investigate students’ attitudes toward this blended learning approach; and (2) to test whether it improved their knowledge about thoracic radiology.MethodsA prospective study was conducted at the local medical center; 156 fourth-year medical students completed this study. Before and after the course, students had to complete (1) questionnaires to investigate their attitudes (7-point Likert scale); and (2) an objective test to assess their knowledge (multiple-choice/free text questions; results as % of correct answers).ResultsRegarding (1), the course led to an improvement in all items compared to baseline, exemplary: interest in thoracic radiology (precourse 4.2 vs. 5.4 postcourse) and the fulfillment of students’ expressed requirements regarding the teaching content (4.5 precourse vs. 6.2 postcourse). Furthermore, the great majority (88%) of our participants wished for more online learning offerings in the future. Regarding (2), the course led to improved knowledge on the objective test (precourse: 40% vs. postcourse: 63% correct answers).ConclusionThis feasibility study showed the successful design and implementation of a blended learning approach in thoracic radiology. Furthermore, it revealed medical students’ positive attitudes toward this approach and showed an increased knowledge in thoracic radiology. Thus, such approaches might be used to enrich the teaching armamentarium in medical education and to further enhance interest and knowledge in thoracic diseases among medical students.
The ability of digital breast tomosynthesis to reduce additional examinations in older women
Authors: Gharaibeh Maha , Alfwares Ahmad Abu , Elobeid Eyhab , Khasawneh Ruba , Rousan Liqa , El-Heis Mwaffaq , Al-Jarrah Mooath , Haj Hussein Ahmed A. , Altalhi Maryam , Abualigah Laith 
Published: November 2023

AimsTo assess the diagnostic performance of digital breast tomosynthesis (DBT) in older women across varying breast densities and to compare its effectiveness for cancer detection with 2D mammography and ultrasound (U/S) for different breast density categories. Furthermore, our study aimed to predict the potential reduction in unnecessary additional examinations among older women due to DBT.MethodsThis study encompassed a cohort of 224 older women. Each participant underwent both 2D mammography and digital breast tomosynthesis examinations. Supplementary views were conducted when necessary, including spot compression and magnification, ultrasound, and recommended biopsies. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated for 2D mammography, DBT, and ultrasound. The impact of DBT on diminishing the need for supplementary imaging procedures was predicted through binary logistic regression.ResultsIn dense breast tissue, DBT exhibited notably heightened sensitivity and NPV for lesion detection compared to non-dense breasts (61.9% vs. 49.3%, p &lt; 0.001) and (72.9% vs. 67.9%, p &lt; 0.001), respectively. However, the AUC value of DBT in dense breasts was lower compared with non-dense breasts (0.425 vs. 0.670). Regarding the ability to detect calcifications, DBT demonstrated significantly improved sensitivity and NPV in dense breasts compared to non-dense breasts (100% vs. 99.2%, p &lt; 0.001) and (100% vs. 94.7%, p &lt; 0.001), respectively. On the other hand, the AUC value of DBT was slightly lower in dense breasts compared with non-dense (0.682 vs. 0.711). Regarding lesion detection for all cases between imaging examinations, the highest sensitivity was observed in 2D mammography (91.7%, p &lt; 0.001), followed by DBT (83.7%, p &lt; 0.001), and then ultrasound (60.6%, p &lt; 0.001). In dense breasts, sensitivity for lesion detection was highest in 2D mammography (92.9%, p &lt; 0.001), followed by ultrasound (76.2%, p &lt; 0.001), and the last one was DBT. In non-dense breasts, sensitivities were 91% (p &lt; 0.001) for 2D mammography, 50.7% (p &lt; 0.001) for ultrasound, and 49.3% (p &lt; 0.001) for DBT. In terms of calcification detection, DBT displayed significantly superior sensitivity compared to 2D mammography in both dense and non-dense breasts (100% vs. 91.4%, p &lt; 0.001) and (99.2% vs. 78.5%, p &lt; 0.001), respectively. However, the logistic regression model did not identify any statistically significant relationship (p &gt; 0.05) between DBT and the four dependent variables.ConclusionOur findings indicate that among older women, DBT does not significantly decrease the requirement for further medical examinations.
Effect of host shift on the gut microbes of Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae)
Authors: Tian Zhenya , Chen Lixiang , Chen Guangmei , Wang Jingjing , Ma Chao , Zhang Yan , Gao Xuyuan , Chen Hongsong , Zhou Zhongshi 
Published: November 2023

BackgroundGut microbes play an important role in the adaptation of insects. Polyphagous insects usually undergo changes in gut microbiota after host shift. The Bactrocera cucurbitae have a wide range of hosts, but the dynamic of gut microorganisms during host shift have not been thoroughly investigated. To understand the role of gut microbes in insect adaptation, it is necessary to study the dynamics of insect gut microorganisms during host transfer.MethodsUsing Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae) and its four hosts as study subjects, we investigated the dynamics of gut microbes during host transfer and the effects of different hosts on the gut microbial composition of B. cucurbitae.ResultsThe results showed that the Chao1 index of B. cucurbitae decreased significantly during host transfer, and the intestinal microorganisms were significantly affected by the original host, host, and generations. Furthermore, predicated changes in the abundance of secondary metabolite pathways after host transfer suggested that microorganisms may play an important role in the degradation of secondary metabolites, among which Providencia and Morganella have important functions in the gut of B. cucurbitae.ConclusionThis implied that microorganisms play a function in the host transfer process of B. cucurbitae and may be an important cofactor in the adaptation of B. cucurbitae to different hosts and environments, providing new research ideas for the future control of B. cucurbitae.
Examining the role of participant and study partner report in widely-used classification approaches of mild cognitive impairment in demographically-diverse community dwelling individuals: results from the Einstein aging study
Authors: Chang Katherine H. , Wang Cuiling , Nester Caroline O. , Katz Mindy J. , Byrd Desiree A. , Lipton Richard B. , Rabin Laura A. 
Published: November 2023

ObjectiveThe role of subjective cognitive concerns (SCC) as a diagnostic criterion for MCI remains uncertain and limits the development of a universally (or widely)-accepted MCI definition. The optimal MCI definition should define an at-risk state and accurately predict the development of incident dementia. Questions remain about operationalization of definitions of self- and informant-reported SCCs and their individual and joint associations with incident dementia.MethodsThe present study included Einstein Aging Study participants who were non-Hispanic White or Black, free of dementia at enrollment, had follow-up, and completed neuropsychological tests and self-reported SCC at enrollment to determine MCI status. Informant-reported SCC at baseline were assessed via the CERAD clinical history questionnaire. Self-reported SCC were measured using the CERAD, items from the EAS Health Self-Assessment, and the single memory item from the Geriatric Depression Scale. Cox proportional hazards models examined the association of different operationalizations of SCC with Petersen and Jak/Bondi MCI definitions on the risk of dementia, further controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at specific time points for each definition, and Youden’s index were calculated as an accuracy measure. Cox proportional hazards models were also used to evaluate the associations of combinations of self- and informant-reported SCC with the risk of incident dementia.Results91% of the sample endorsed at least one SCC. Youden’s index showed that not including SCC in either Jak/Bondi or Petersen classifications had the best balance between sensitivity and specificity across follow-up. A subset of individuals with informants, on average, had a lower proportion of non-Hispanic Blacks and 94% endorsed at least one self-reported SCC. Both informant-reported and self-reported SCC were significantly associated with incident dementia.ConclusionOur findings suggest that the SCC criterion may not improve the predictive validity for dementia when included in widely-employed definitions of MCI. Consistent with some prior research, informant-reported SCC was more related to risk of incident dementia than self-reported SCC. Given that requiring informant report as a diagnostic criterion may unintentionally exclude health disparate groups, additional consideration is needed to determine how best to utilize informant-report in MCI diagnosis.
Risk factors and a prediction model for the prognosis of intracerebral hemorrhage using cerebral microhemorrhage and clinical factors
Authors: Feng Hao , Wang Xin , Wang Wenjuan , Zhao Xingquan 
Published: November 2023

BackgroundThis study aimed to identify the risk factors and construct a prediction model for the prognosis of intracerebral hemorrhage (ICH) at discharge, 3 months, and 12 months.MethodsA total of 269 patients with ICH were retrospectively enrolled at our hospital between January 2014 and August 2016. The prognosis of ICH was assessed using the modified Rankin Scale (mRS); an mRS score &gt; 2 was considered a poor outcome. The primary endpoint was the 3-month mRS, whereas the secondary endpoints included the mRS scores at discharge and 12 months, and mortality.ResultsThe Glasgow Coma Scale (GCS), National Institutes of Health (NIH) stroke scale, International Normalized Ratio (INR), blood urea nitrogen (BUN), epencephalon hemorrhage, and primary hematoma volume were significantly associated with a poor mRS score at 3 months. The predictive value of the prediction model based on these factors for a poor mRS score was 87.8%. Furthermore, a poor mRS score at discharge was affected by the GCS, NIH stroke scale, and primary hematoma volume; the constructed model based on these factors had a predictive value of 87.6%. In addition, the GCS, NIH stroke scale, and surgery were significantly related to a poor mRS score at 12 months; the predictive value of the constructed model based on the aforementioned factors for a poor mRS score was 86.5%. Finally, primary hematoma volume is significantly associated with the risk of 12 months mortality.ConclusionsThe study identified risk factors and constructed a prediction model for poor mRS scores and mortality at discharge, 3 and 12 months in patients with ICH. The prediction models for mRS scores showed a relatively high predictive performance.
Altered electrophysiology mechanism related to inhibitory control in adults with insomnia
Authors: Ding Xiaobin , He Liang , Geng Xicong , Zhao Xuan , He Zijing , Zhang Xiangzi 
Published: November 2023

BackgroundInsomnia disorder (ID), one of the most common psychophysiological disorders, can cause a serious burden on the individual's work and academic performance. Cognitive dysfunction often exists in patients with insomnia, which negatively affects their living quality. Inhibitory control (IC), as a vital cognitive function, allows individuals to suppress attention, behavior, or thoughts that are irrelevant to the task, so as to effectively adapt to the current goal. The earlier studies on the inhibitory control of insomnia patients predominantly used subjective scales for evaluation and that can have drawbacks because they don't provide an objective assessment.MethodsIn order to investigate the inhibitory control function of insomniacs, this research subdivides inhibitory control into response inhibition and conflict inhibition. The response inhibition and conflict inhibition capacities of insomniacs were evaluated using the two-choice oddball task and the color-word stroop task, and accordingly the association between insomnia disorder and inhibitory control capacity as well as its cognitive neural mechanism was able to be examined.ResultsBehavioral results finding, insomniacs conducted the two-choice oddball test and the color-word stroop task with lower accuracy and slower reaction times when compared to healthy sleepers. ERP results finding, when performing the two-choice oddball task, the P3 amplitude of the insomniacs was significantly lower than that of healthy sleepers while there was no significant difference between the two groups' N2 amplitudes. At the same time, when completing the color-word stroop task, the insomniacs' N450 amplitude was significantly lower than that of healthy sleepers.DiscussionThe above findings suggest that in response inhibition tasks, insomniacs may have weaker motor inhibition abilities, and similarly perform weaker conflict monitoring abilities in conflict inhibition tasks, which indicates that insomniacs' inhibitory control is impaired compared to that of healthy sleepers. This study thus relates to the finding at the electrophysiological level that there is a certain correlation between insomnia and a decline in inhibitory control ability, which may suggest that improving inhibitory control function in patients with insomnia is a clinically significant and worthwhile area of adjuvant treatment.
New characterization of dihydroergotamine receptor pharmacology in the context of migraine: utilization of a β-arrestin recruitment assay
Authors: McConnachie Lisa , Goadsby Peter J. , Vann Robert E. , Ray Sutapa , Shrewsbury Stephen B. , Aurora Sheena K. 
Published: November 2023

IntroductionDihydroergotamine mesylate (DHE) is an established effective acute therapy for migraine and is often characterized by its broad receptor pharmacology. Knowledge of DHE pharmacology largely comes from studies employing older methodologies.ObjectiveTo assess DHE receptor activity using high-throughput methods to screen for functional ß-arrestin activity at G protein–coupled receptors (GPCRs).MethodsFunctional receptor activities of DHE and sumatriptan succinate (both 10 μM) were screened against 168 GPCRs using the gpcrMAX assay. Agonist and antagonist effects were considered significant if receptor activity was &gt;30% or inhibited by &gt;50%, respectively. Radiolabeled ligand binding assays were performed for DHE (0.01–300 nM for 5-HT3 and 4E; 0.3–10,000 nM for 5-HT1B, α-adrenergic2B [i.e., α2B-adrenoceptor], D2, and D5) to assess specific binding to select receptors.ResultsDHE (10 μM) exhibited agonist activity at α-adrenergic2B, CXC chemokine receptor 7 (CXCR7), dopamine (D)2/5, and 5-hydroxytryptamine (5-HT)1A/1B/2A/2C/5A receptors and antagonist activity at α-adrenergic1B/2A/2C (i.e., α1B/2A/2C-adrenoceptors), calcitonin receptor–receptor activity modifying protein 2 (CTR-RAMP2) or amylin 2 (AMY2), D1/3/4/5, and 5-HT1F receptors. Sumatriptan succinate (10 μM) exhibited agonist activity at the 5-HT1B/1E/1F/5A receptors. DHE demonstrated a half-maximal inhibitory concentration (IC50) of 149 nM at the 5-HT1F receptor and a half-maximal effective concentration (EC50) of 6 μM at the CXCR7 receptor. DHE did not bind to the 5-HT3 receptor at concentrations up to 300 nM and bound poorly to 5-HT4E and D5 receptors (IC50 of 230 and 370 nM, respectively). DHE bound strongly to the D2, 5-HT1B, and α-adrenergic2B receptors (IC50 of 0.47, 0.58, and 2.8 nM, respectively).ConclusionBy using a high-throughput β-arrestin recruitment assay, this study confirmed the broad receptor profile of DHE and provided an update on DHE receptor pharmacology as it relates to migraine.
Association between dietary antioxidant indices and glaucoma in the National Health and Nutrition Examination Survey
Authors: Li Wenwei , Wang Bin 
Published: November 2023

ObjectiveTo explore the relationship between dietary antioxidant indices (DAI) and glaucoma using the data from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES).MethodsOur study comprised participants who completed the NHANES dietary intake interview and visual health questionnaire at age 40 or older. The intakes of the vitamins A, C, and E as well as of zinc, selenium, and magnesium were used to generate the DAI, which represents the overall antioxidant qualities. The self-report method for glaucoma diagnosis (ever been told by an eye doctor) was used. Survey logistic regression analyses were employed to investigate the association between DAI and glaucoma.ResultsA total of 6,128 participants were included in our study. The unadjusted model’s findings revealed a negative correlation between dietary antioxidant indices and self-reported glaucoma [0.93 (0.90, 0.96), p &lt; 0.0001]. For every unit increase in dietary antioxidant indices, the risks of self-reported glaucoma in model 1 (adjusted for age, sex, race, marital status and PIR) decreased by 5% [0.95 (0.90, 0.99), p = 0.02]. After adjusting all the covariates (model 2), the risks of self-reported glaucoma decreased by 6% [0.94 (0.90, 0.99), p = 0.02] for each unit increase of dietary antioxidant indices. After converting DAI into classified variables (tertile), the same trend was found (p = 0.001).ConclusionIn this analysis of the NHANES database, we found higher dietary antioxidant indices were associated with lower risk of glaucoma.