bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery and preclinical evaluation of BPB-101: a novel triple functional bispecific antibody targeting GARP-TGF-β complex/SLC, free TGF-β and PD-L1
Authors: Xu Wenxin , Xu Jieying , Li Pingcui , Xu Deyu , Cheng Hongjie , Zheng Huan , Zhang Li , Liu Mengmeng , Ye Siyuan , Jiang Mengshi , Yu Wenqi , Wang Jiabing , Ding Lieming 
Published: November 2024

BackgroundIn the tumor microenvironment (TME), the transforming growth factor-β (TGF-β) and programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling axes are complementary, nonredundant immunosuppressive signaling pathways. Studies have revealed that active TGF-β is mainly released from the glycoprotein A repetitions predominant (GARP)-TGF-β complex on the surface of activated regulatory T cells (Tregs), B cells, natural killer (NK) cells, and tumor cells. The currently available antibodies or fusion proteins that target TGF-β are limited in their abilities to simultaneously block TGF-β release and neutralize active TGF-β in the TME, thus limiting their antitumor effects.MethodsWe designed and constructed a bispecific, trifunctional antibody, namely, BPB-101, that specifically targets the GARP-TGF-β complex and/or small latent complex (SLC), active TGF-β, and PD-L1. The binding ability of BPB-101 to the different antigens was determined by ELISA, FACS, and biolayer interferometry (BLI). The blocking ability of BPB-101 to the TGF-β and PD-1/PD-L1 signaling axes was determined by reporter gene assay (RGA). The antitumor effect and biosafety of BPB-101 were determined in a transgenic mouse tumor model and cynomolgus monkeys, respectively. Stability assessments, including stability in serum, after exposure to light, after repeated freeze-thaw cycles, and after high-temperature stress tests had been completed to evaluate the stability of BPB-101.ResultsBPB-101 bound efficiently to different antigenic proteins: the GARP-TGF-β complex and/or SLC, active TGF-β, and PD-L1. Data showed that BPB-101 not only effectively inhibited the release of TGF-β from human Tregs, but also blocked both the TGF-β and PD-1/PD-L1 signaling pathways. In an MC38-hPD-L1 tumor-bearing C57BL/6-hGARP mouse model, BPB-101 at a dose of 5 mg/kg significantly inhibited tumor growth, with a complete elimination rate of 50%. Stability assessments confirmed the robustness of BPB-101. Furthermore, BPB-101 showed a favorable safety profile in nonhuman primate (NHP) toxicity studies.ConclusionBPB-101 is a potentially promising therapeutic candidate that may address unmet clinical needs in cancer immunotherapy, thus, BPB-101 warrants further clinical investigation.
Prevalence of hybrid TLR4+M2 monocytes/macrophages in peripheral blood and lung of systemic sclerosis patients with interstitial lung disease
Authors: Gotelli Emanuele , Soldano Stefano , Feghali-Bostwick Carol , Montagna Paola , Campitiello Rosanna , Contini Paola , Mora Marco , Benelli Roberto , Hysa Elvis , Paolino Sabrina , Pizzorni Carmen , Sulli Alberto , Smith Vanessa , Cutolo Maurizio 
Published: November 2024

IntroductionSystemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular damage, immune system reactivity and progressive fibrosis of skin and internal organs. Interstitial lung disease is the leading cause of death for SSc patients (SSc-ILD), and the process of lung fibrosis involves also circulating monocytes and alveolar macrophages.MethodsCurrent study aimed to identify monocyte/macrophage phenotypes in lung and peripheral blood of SSc-ILD patients by immunostaining and flow cytometry, respectively. Single immunostaining was performed using primary antibodies against CD68 (pan-macrophage marker), CD80, CD86, TLR4 (M1 markers), CD163, CD204, and CD206 (M2 markers). Flow cytometry analysis included the evaluation of CD45, CD14, CD16 (monocyte lineage), CD1c (dendritic lineage), together with M1 and M2 activation markers on circulating monocytes. Protein synthesis of TLR4 and M2 markers was also investigated in cultured monocytes-derived macrophages (MDMs) from SSc-ILD patients by Western Blotting.ResultsLung samples were obtained from 9 SSc-ILD patients (50 ± 9 years old) and 5 control non-SSc patients without lung fibrosis (58 ± 23 years old). Alveolar macrophages (CD68+ cells) showed a significantly higher positivity of M1 and M2 markers in SSc-ILD lung samples than in controls (p&lt;0.05 for CD80, p&lt;0.01 for CD86, p&lt;0.001 for CD68, p&lt;0.0001 for TLR4, CD163, CD204 and CD206). In CD68 positive areas of SSc-ILD samples, a significantly higher percentage of TLR4, CD163, CD204, and CD206 positive cells was observed compared to CD80 and CD86 positive cells (p&lt;0.001 in both cases), suggesting the possible presence of hybrid TLR4+M2 macrophages (CD68+CD80-CD86-TLR4+CD163+CD204+CD206+cells) in SSc-ILD samples. A second cohort of 26 SSc-ILD patients (63 ± 14 years old) and 14 SSc patients without ILD (63 ± 19 years old) was recruited for flow cytometry analysis of circulating monocytes. Again, a significantly higher percentage of hybrid TLR4+M2 monocytes (CD1c-CD80-TLR4+CD163+CD204+CD206+cells) was found in SSc-ILD positive than SSc-ILD negative patients (p&lt;0.05). Moreover, the protein synthesis of TLR4 and M2 markers was also found higher in cultured MDMs obtained from SSc-ILD patients than in MDMs from SSc patients without ILD and this increase was significantly higher for CD163 (p&lt;0.05) and CD206 (p&lt;0.01).ConclusionsThe presence of hybrid TLR4+M2 markers on both circulating monocytes and resident lung macrophages in SSc-ILD patients, is reported for the first time. Therefore, the detection of circulating hybrid TLR4+M2 monocytes in SSc-ILD might represent a further potential biomarker of progressive organ fibrosis, to be searched in blood samples of SSc patients.
The time course of syllable frequency effects in the visual recognition of Korean morphologically complex nouns: an ERP study
Authors: Kwon Seoyeon , Lee Solbin , Kim Joonwoo , Nam Kichun 
Published: November 2024

IntroductionThe syllable frequency effect refers to that during the lexical decision task, words beginning with high-frequency syllables elicit slower responses than words beginning with low-frequency ones, indicating an inhibitory effect. However, previous studies in Korean have yielded mixed results. For morphologically simple words, an inhibitory or null effect has been observed, whereas in morphologically complex words, a facilitative effect has been reported. Unfortunately, the explanations for these mixed findings remain unclear. This study employed both behavioral and electrophysiological methods to investigate the temporal dynamics of the facilitative syllable frequency effect in Korean morphologically complex nouns. A secondary aim was to explore whether syllable frequency is modulated by stem length as a factor in morphological processing, at both the behavioral and neurophysiological levels.MethodsTwenty-eight participants (mean age = 25.14, 9 female) performed a lexical decision task, responding whether visually presented stimuli were valid Korean words, while EEG data were recorded. The experimental condition included syllable frequency (2: High vs. low) and stem length (2: Long vs. Short).ResultsThe behavioral data showed that lexical decision latencies were faster for morphologically complex nouns with higher syllable frequencies compared to those with lower frequencies. The ERP data revealed a significant syllable frequency effect on the P300 component, reflecting early visual word processing. However, no significant effect was found in the N400 component. Although stem length did not significantly influence behavioral results, it did show significant differences in N250 amplitudes. Notably, an interaction between syllable frequency and stem length had a significant effect on N400, in contrast to the behavioral findings.DiscussionsThe findings suggest that, in the processing of morphologically complex words in Korean, syllable frequency serves as partial information that facilitates lexical decisions through the fast-guess mechanism, as proposed by the MROM-S model. Furthermore, the delayed time window for syllable processing may stemmed from a different stage of the processing between morphologically complex words and morphologically simple words. Lastly, stem length, as a form of morphological processing, may interact with syllable frequency during the lexical access stage.
Enhancing critical care practitioners’ knowledge and adherence to ventilator-associated events bundle: a comprehensive analysis
Authors: Alanazi Samiyah , Alonazi Wadi B. 
Published: November 2024

ObjectivesFew surveys have focused on ventilator-associated pneumonia occurring in critically ill patients undergoing intubation and mechanical ventilation. Limited knowledge among healthcare workers may impede compliance with evidence-based guidelines for preventing ventilator-associated pneumonia. We evaluate the knowledge of intensive care professionals related to preventing ventilator-associated pneumonia in the intensive care units.DesignCross-sectional survey.SettingAdult critical care departments in four tertiary hospitals in Riyadh in Saudi Arabia.SubjectsAdult intensive care units attending physicians (intensivist, non-intensivist), Nurses, and Respiratory Therapist who works in ICUs.Measurement and main resultsWe analyzed 758 questionnaires (100% response rate) from four tertiary hospitals in Riyadh provinces. Nurses constitute the largest group, with most of all professions being Saudi nationals at [343(45.3%)]. Physicians are primarily male, accounting for [127(16.8%)], while the Respiratory Therapy field is predominantly female at [91(12%)]. Our analysis involved, chi-square test to explore potential variations in knowledge among participants with diverse demographic variables. The finding of this was significant positive correlation between some elements. It provides valuable insights into the intricate associations between demographic characteristics and healthcare practices related to VAP prevention (p &lt; 0.05). Demographic factors significantly influence health practices related to ventilator associated pneumonia bundle prevention.ConclusionOur research identifies key factors influencing ventilator associated pneumonia prevention in critical care settings and provides actionable recommendations for healthcare institutions to enhance patient safety. While this research has extensively examined physicians, nurses and respiratory therapists, there is a depth of investigations comparing the knowledge and practices of these specialists within tertiary hospitals in Riyadh. Conducting such a study is imperative to address knowledge gaps and promote practices that mitigate the adverse outcomes of ventilator associated pneumonia on healthcare systems. This study underscores the pivotal role of education, professional experience, and demographic factors in shaping medical procedures and practices. Targeted interventions in these areas could potentially enhance adherence to the bundle. The study suggests the importance of targeted education programs, mentorship initiatives, and ongoing research to enhance patient outcomes in critical care settings.
Clinical team debriefing post-critical events: perceptions, benefits, and barriers among learners
Authors: Imperio Michelle , Ireland Kristin , Xu Yiqing , Esteitie Rania , Tan Laren D. , Alismail Abdullah 
Published: November 2024

BackgroundClinical team debriefings (TD) following critical events are pivotal in promoting team learning and enhancing patient outcomes. Despite their importance, perceptions and practices surrounding these debriefings remain under-researched. The purpose of this study was to explore learners’ perceptions and experiences regarding debriefing practices, investigate correlations or discrepancies within those perceptions and experiences, and identify recommendations and potential practice improvements for clinical educators.MethodsThis was a cross-sectional anonymous survey of healthcare professionals, including medical students, medical residents, nursing students, and respiratory therapy students. The survey was sent to respiratory therapy programs, nursing programs, internal and emergency medicine and pediatric residency programs in southern California and Michigan. The variables surveyed included demographics, team debriefing experience, code experience, TD perceptions, emotional status, cognitive load, and the benefits and barriers of conducting post-code TD. Emotional status and cognitive load were assessed using validated surveys by Paas et al. and Barrett and Russell.ResultsOf the 184 participants, 56% (n = 104) were female. The mean cognitive load was 6.14 ± 1.6. A notable negative correlation was found between mental effort in recent real code experiences and emotional scales: “tense: calm” (r = −0.210; p = 0.018), “nervous: relaxed” (r = −0.234; p = 0.008), and “stressed: serene” (r = −0.258; p = 0.004). While 68.5% had attended a cardiopulmonary arrest event, only 34.9 had TD after their most recent code, and only 48.4% reported ever having a post-code TD. Notably, nurses (75.4%) and attending physicians (73.8%) predominated these debriefings. Debriefings averaged 9.30 min (SD = 7.30) with a median of 6 min. The most recognized benefits were identifying areas of systems/process improvement and promoting teamwork and solidarity within the code team participants. The most commonly recognized barriers were lack of time and wanting a more senior person to initiate TD.ConclusionThe results of this study show a relatively low TD occurrence despite the high value learners attribute to TD. Addressing this inconsistency requires structured approaches, dedicated time, and an understanding of barriers. Recognizing the significant cognitive and emotional loads on learners further accentuates the need for structured post-event debriefings. Addressing these challenges with multi-disciplinary participation can enhance debriefing outcomes.
The efficacy and safety of remimazolam in painless colonoscopy: a prospective, randomized clinical trial
Authors: Shi Haobing , Zhang Jinyuan , Hu Zhiqiang , Hou Qianhao , Hu Qianhua , Dai Zhiguang , Zhou Wenjuan , Qi Dingwu , Li Yuling , Wang Qing , Wang Xiangrui , Liao Lijun , Qian Shuwen 
Published: November 2024

PurposeRemimazolam is a new type of ultra-short-effect intravenous anesthetic, that may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. The aim of this clinical study was to compare the efficacy and safety of two different doses of remimazolam with propofol for sedation during colonoscopy.Patients and methods225 subjects, aged 18 to 80 years, with American Society of Anesthesiology physical status I-III, were scheduled to undergo colonoscopy. All the subjects were randomly assigned to three groups, Low-Rem group (low dose remimazolam, 0.15 mg/kg, iv, n = 75), High-Rem group (high dose remimazolam, 0.2 mg/kg, iv, n = 75), and Propofol group (propofol 2 mg/kg, iv, n = 75). Every individual in this trial was given nalbuphine hydrochloride (0.2 mg/kg, iv) before administration of remimazolam or propofol. The primary outcome was the success rate of sedation. Haemodynamic parameters and adverse events were recorded to evaluate safety. Satisfaction of sedation from patients, anesthesiologists and gastroenterologists were also recorded.ResultsThe success rate of colonoscopy procedure was 100% in both High-Rem and Propofol groups, but it was 89% in Low-Rem group (p &lt; 0.05). Furthermore, the induction time of anesthesia was shorter in Propofol group, when compared to the Low-Rem group and the High-Rem group (p &lt; 0.05). The recovery time in Low-Rem group, High-Rem group, and Propofol group was 2.33, 2.43, and 3.21 min (p &lt; 0.05) respectively, and the time of discharge was 25.00, 25.01, and 27.56 min (p &lt; 0.05) respectively. Simultaneously, the incidence of adverse events such as hypotension, bradycardia, and respiratory depression in the remimazolam groups were significantly lower than that in the propofol group. No significant differences were observed among the three groups in Ramsay scale, BPS-NI scale, and Limb movement classification. Moreover, patients, anesthesiologists, and gastroenterologists were all satisfied with the sedation process.ConclusionRemimazolam can be used safely and effectively for colonoscopy. 0.2 mg/kg remimazolam and propofol have the same sedation success rate and more stable hemodynamics and fewer side effects than propofol.Clinical trial registrationChiCTR2100054053.
Attitudes toward and exposure to gender discrimination in work life by pulmonologists and thoracic surgeons: a questionnaire-based survey among Turkish thoracic society members
Authors: Ocakli Birsen , Yorgancioglu Arzu , Gungor Sinem , Topcu Fusun , Senol Yesim Yigiter , Goktas Basak , Kokturk Nurdan , Tuncay Eylem , Gundogus Baran , Altinoz Hilal , Yasin Yesim , Ozmen Ipek , Duru Serap , Yildirim Elif Ozari , Sevim Tulin , Ozturk Cansel Atinkaya , Uzaslan Esra ,   the Turkish Thoracic Society Women and Lung Diseases Working Group
Published: November 2024

BackgroundThis study aimed to evaluate attitudes toward and exposure to gender discrimination in work life by chest diseases specialists and thoracic surgeons.MethodsA total of 275 members of Turkish Thoracic Society (TTS) were included on a voluntary basis in this online cross-sectional questionnaire-survey using an internal member-only social media platform of TTS. The questionnaire form elicited items on sociodemographic characteristics, occupational characteristics and gender discrimination in work life (general opinions, attitudes and exposure).ResultsFemale doctors (vs. males) were less likely to be a thoracic surgeon (13.8% vs. 34.5%, p &lt; 0.05) and a professor of thoracic surgery (0.0% vs. 26.7% vs. p &lt; 0.05), and more likely to consider housework as a considerable burden (89.8 vs. 73.6%, p = 0.02) and the significant role of discriminatory, negative and dissuasive attitudes of male physicians in their career choice (67.6 vs. 35.6%, p = 0.039). Male doctors were more likely to considered that men are more successful in specialties that require active physical strength (65.5 vs. 27.7%, p = 0.005) and those with very long working hours and heavy shifts (57.5 vs. 39.4%, p = 0.001). Female thoracic surgeons were more likely than males to consider that specialties with very long working hours and heavy shifts are more suitable for men (26.9 vs. 6.0%, p = 0.027) and men are given priority in academic career promotion (64.0 vs. 13.3%, p &lt; 0.001). Younger (vs. older) females reported higher rate of exposure to gender discrimination (p = 0.041) and considerable impact of social roles on the specialty (p = 0.007), while female doctors working as a resident (33.8%) and a specialist (50.05%) indicated higher rate of exposure to gender discrimination during their career (p = 0.024).ConclusionIn conclusion, our findings revealed that exposure to gender discrimination in work life was more commonly expressed by female members of TTS, particularly in terms of burden of social roles, career advancement options and leadership positions, along with significant role of discriminatory, negative and dissuasive attitudes of male physicians in their career choice. Accordingly, women remain underrepresented in thoracic surgery, particularly in the academic rank of full professor and in leadership positions with inability to promote after a definite step in their careers.
Recognition of parasitic helminth eggs via a deep learning-based platform
Authors: He Wei , Zhu Huiyin , Geng Junjie , Hu Xiao , Li Yuting , Shi Haimei , Wang Yaqian , Zhu Daiqian , Wang Huidi , Xie Li , Yang Hailin , Li Jian 
Published: November 2024

IntroductionAccurate and rapid diagnosis is crucial for the effective treatment of parasitosis. Traditional etiological methods, especially microscopic examination, are time-consuming, labor-intensive, and prone to false or missed detections. In response to these challenges, this study explores the use of artificial intelligence (AI) for the detection and classification of human parasite eggs through the YOLOv4 deep learning object detection algorithm.MethodsEggs from species such as Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), Enterobius vermicularis (E. vermicularis), Ancylostoma duodenale (A. duodenale), Schistosoma japonicum (S. japonicum), Paragonimus westermani (P. westermani), Fasciolopsis buski (F. buski), Clonorchis sinensis (C. sinensis), and Taenia spp. (T. spp.) were collected and prepared as both single species and mixed egg smears. These samples were photographed under a light microscope and analyzed using the YOLO (You Only Look Once) v4 model.ResultsThe model demonstrated high recognition accuracy, achieving 100% for Clonorchis sinensis and Schistosoma japonicum, with slightly lower accuracies for other species such as E. vermicularis (89.31%), F. buski (88.00%), and T. trichiura (84.85%). For mixed helminth eggs, the recognition accuracy rates arrived at Group 1 (98.10, 95.61%), Group 2 (94.86, 93.28 and 91.43%), and Group 3 (93.34 and 75.00%), indicating the platform’s robustness but also highlighting areas for improvement in complex diagnostic scenarios.DiscussionThe results show that this AI-assisted platform significantly reduces reliance on professional expertise while maintaining real-time efficiency and high accuracy, offering a powerful tool for the diagnosis and treatment of parasitosis. With further optimization, such as expanding training datasets and refining recognition algorithms, this AI system could become a key resource in both clinical and public health efforts to combat parasitic infections.
Sex differences in the association between dietary choline intake and total bone mineral density among adolescents aged 12–19 in the United States
Authors: Gong Hongyang , Jiang Jiecheng , Choi Seok , Huang Shaoqun 
Published: November 2024

BackgroundWhile prior research has established a correlation between dietary choline intake and bone density in the elderly, the relationship in adolescents remains ambiguous. This study seeks to examine the association between dietary choline intake and bone density in American adolescents.MethodsData from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2018 were used in this study, encompassing participants aged 12–19 years. The relationship between dietary choline intake and bone density was assessed using multivariate linear regression models and restricted cubic spline (RCS) models. Subgroup analyses were also performed to investigate differences across various subgroups.Results3,800 participants with an average age of 15 years were included in this study. After adjusting for relevant confounding factors, a positive correlation was observed between dietary choline intake and total bone density in adolescents (95% CI: 0.03–0.17, p = 0.010). Gender-specific analysis indicated a significant positive correlation between dietary choline intake and total bone density in males (95% CI: 0.07–0.23, p &lt; 0.001), while no significant correlation was found in females (95% CI: −0.19 to 0.09, p = 0.500). The stratified analysis revealed that the positive association was more pronounced in males and non-Hispanic whites (interaction p &lt; 0.05). The restricted cubic spline model demonstrated a linear positive correlation between dietary choline intake and total bone density.ConclusionThis study demonstrates that dietary choline intake levels are positively correlated with bone density in adolescents, with this association being specific to males.