bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trastuzumab deruxtecan (T-DXd) in patients with HER2-mutant metastatic non–small cell lung cancer (mNSCLC): Final analysis results of DESTINY-Lung02.
Authors: Janne Pasi A. , Goto Yasushi , Kubo Toshio , Ninomiya Kiichiro , Kim Sang-We , Planchard David , Ahn Myung-Ju , Smit Egbert F. , De Langen Adrianus Johannes , Perol Maurice , Pons-Tostivint Elvire , Novello Silvia , Hayashi Hidetoshi , Shimizu Junichi , Kim Dong-Wan , Pereira Kaline , Cheng Fu-Chih , Taguchi Ayumi , Cheng Yingkai , Goto Koichi 
Published: June 2024

8543 Background: In the DESTINY-Lung02 primary analysis (data cutoff, Dec 23, 2022), T-DXd 5.4 mg/kg and 6.4 mg/kg demonstrated strong and durable responses and an acceptable and generally manageable safety profile in patients with previously treated HER2 ( ERBB2)-mutant ( HER2m) mNSCLC (Goto et al. 2023). We report updated efficacy and safety results from the final analysis of DESTINY-Lung02. Additional analyses, including data on clinically relevant subgroups and patient-reported outcomes, are planned for presentation. Methods: In this randomized, blinded, multicenter, phase 2 trial, patients with previously treated HER2m mNSCLC were randomly assigned 2:1 to receive T-DXd 5.4 mg/kg or 6.4 mg/kg once every 3 weeks. The primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR), and key secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. The study was not powered to statistically compare the 2 doses. Results: Patients were randomly assigned to T-DXd 5.4 mg/kg (n = 102) or 6.4 mg/kg (n = 50). At the final analysis data cutoff (Aug 25, 2023), the median duration of follow-up (range) was 15.8 months (mo) (1.1-28.6) and 16.5 mo (0.6-28.7) with T-DXd 5.4 and 6.4 mg/kg, respectively (additional 8 mo follow-up since last DCO). Updated efficacy results are presented in the table. After a median treatment duration (range) of 7.7 mo (0.7-27.6) and 8.3 mo (0.7-24.0) with T-DXd 5.4 and 6.4 mg/kg, respectively, drug-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 39.6% (40/101) and 60.0% (30/50) of patients in each arm. Lower rates of drug-related TEAEs associated with drug discontinuation (14.9% [15/101]), dose reduction (16.8% [17/101]), and drug interruption (30.7% [31/101]) were observed with T-DXd 5.4 mg/kg than 6.4 mg/kg (26.0% [13/50], 34.0% [17/50], and 54.0% [27/50], respectively). Adjudicated drug-related interstitial lung disease (ILD)/pneumonitis was reported in 14.9% (15/101) and 32.0% (16/50) of patients in the T-DXd 5.4 and 6.4 mg/kg arms, respectively; most events were grade 1 or 2 (1 grade 5 event in each arm). Conclusions: In this final analysis, T-DXd 5.4 and 6.4 mg/kg continued to show strong and durable responses, which was consistent with the primary analysis, and no significant changes in toxicity were observed with longer follow-up. The approved T-DXd 5.4 mg/kg dose was associated with a more favorable benefit-risk profile and a reduced incidence of adjudicated drug-related ILD/pneumonitis. Clinical trial information: NCT04644237 . [Table: see text]
BF170 hydrochloride enhances the emergence of hematopoietic stem and progenitor cells
Authors: Liu WenYe , Ding YuYan , Shen Zheng , Xu Cong , Yi William , Wang Ding , Zhou Yi , Zon Leonard I. , Liu Jing-Xia 
Published: June 2024

ABSTRACT
Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere cell culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.
High-throughput assays to assess variant effects on disease
Authors: Ma Kaiyue , Gauthier Logan O. , Cheung Frances , Huang Shushu , Lek Monkol 
Published: June 2024

ABSTRACT
Interpreting the wealth of rare genetic variants discovered in population-scale sequencing efforts and deciphering their associations with human health and disease present a critical challenge due to the lack of sufficient clinical case reports. One promising avenue to overcome this problem is deep mutational scanning (DMS), a method of introducing and evaluating large-scale genetic variants in model cell lines. DMS allows unbiased investigation of variants, including those that are not found in clinical reports, thus improving rare disease diagnostics. Currently, the main obstacle limiting the full potential of DMS is the availability of functional assays that are specific to disease mechanisms. Thus, we explore high-throughput functional methodologies suitable to examine broad disease mechanisms. We specifically focus on methods that do not require robotics or automation but instead use well-designed molecular tools to transform biological mechanisms into easily detectable signals, such as cell survival rate, fluorescence or drug resistance. Here, we aim to bridge the gap between disease-relevant assays and their integration into the DMS framework.
TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling
Authors: Shan Ke Zoe , Le Trieu , Liang Pengfei , Dong Ping , Lowry Augustus J. , Kremmyda Polina , Claesson-Welsh Lena , Yang Huanghe 
Published: June 2024

ABSTRACT
TMEM16F (also known as ANO6), a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes, such as blood coagulation, neurodegeneration, cell–cell fusion and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight the role of intracellular signaling by TMEM16F in endothelial cells but also open new avenues for exploring the regulatory mechanisms for membrane lipid asymmetry and their implications in disease pathogenesis.
Desmosomes at a glance
Authors: Perl Abbey L. , Pokorny Jenny L. , Green Kathleen J. 
Published: June 2024

ABSTRACT
Desmosomes are relatives of ancient cadherin-based junctions, which emerged late in evolution to ensure the structural integrity of vertebrate tissues by coupling the intermediate filament cytoskeleton to cell–cell junctions. Their ability to dynamically counter the contractile forces generated by actin-associated adherens junctions is particularly important in tissues under high mechanical stress, such as the skin and heart. Much more than the simple cellular ‘spot welds’ depicted in textbooks, desmosomes are in fact dynamic structures that can sense and respond to changes in their mechanical environment and external stressors like ultraviolet light and pathogens. These environmental signals are transmitted intracellularly via desmosome-dependent mechanochemical pathways that drive the physiological processes of morphogenesis and differentiation. This Cell Science at a Glance article and the accompanying poster review desmosome structure and assembly, highlight recent insights into how desmosomes integrate chemical and mechanical signaling in the epidermis, and discuss desmosomes as targets in human disease.
PTEN and the PTEN-like phosphatase CnrN have both distinct and overlapping roles in a Dictyostelium chemorepulsion pathway
Authors: Consalvo Kristen M. , Rijal Ramesh , Beruvides Steven L. , Mitchell Ryan , Beauchemin Karissa , Collins Danni , Scoggin Jack , Scott Jerome , Gomer Richard H. 
Published: June 2024

ABSTRACT
Little is known about eukaryotic chemorepulsion. The enzymes phosphatase and tensin homolog (PTEN) and CnrN dephosphorylate phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Dictyostelium discoideum cells require both PTEN and CnrN to induce chemorepulsion of cells away from the secreted chemorepellent protein AprA. How D. discoideum cells utilize two proteins with redundant phosphatase activities in response to AprA is unclear. Here, we show that D. discoideum cells require both PTEN and CnrN to locally inhibit Ras activation, decrease basal levels of PI(3,4,5)P3 and increase basal numbers of macropinosomes, and AprA prevents this increase. AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes. PTEN, but not CnrN, decreases basal levels of PI(4,5)P2, and AprA requires PTEN, but not CnrN, to induce cell roundness. Together, our results suggest that CnrN and PTEN play unique roles in AprA-induced chemorepulsion.
Persistent Pain After Breast Cancer Treatment, an Underreported Burden for Breast Cancer Survivors
Authors: Strijbos Bo T. M. , Janssen Loes , Voogd Adri C. , Zwaans Willem A. R. , Roumen Rudi M. H. , Maaskant-Braat Adriana J. G. 
Published: June 2024

Abstract
Background
Many patients who have undergone surgery experience persistent pain after breast cancer treatment (PPBCT). These symptoms often remain unnoticed by treating physician(s), and the pathophysiology of PPBCT remains poorly understood. The purpose of this study was to determine prevalence of PPBCT and examine the association between PPBCT and various patient, tumor, and treatment characteristics.

Patients and Methods
We conducted a questionnaire-based cross-sectional study enrolling patients with breast cancer treated at Máxima Medical Center between 2005 and 2016. PPBCT was defined as pain in the breast, anterior thorax, axilla, and/or medial upper arm that persists for at least 3 months after surgery. Tumor and treatment characteristics were derived from the Dutch Cancer Registry and electronic patient files.

Results
Between February and March 2019, a questionnaire was sent to 2022 women, of whom 56.5% responded. Prevalence of PPBCT among the responders was 37.9%, with 50.8% reporting moderate to severe pain. Multivariable analyses showed that women with signs of anxiety, depression or a history of smoking had a higher risk of experiencing PPBCT. Women aged 70 years or older at diagnosis were significantly less likely to report PPBCT compared with younger women. No significant association was found between PPBCT and treatment characteristics, including type of axillary surgery and radiotherapy.

Conclusions
A considerable percentage of patients with breast cancer experience PPBCT. Women with signs of anxiety or depression and women with a history of smoking are more likely to report PPBCT. Further research is required to understand the underlying etiology and to improve prevention and treatment strategies for PPBCT.
Hypertrophic pachymeningitis, associated with eosinophilic granulomatosis with polyangiitis, and ANCA-negative serology
Authors: Martínez-Piña Daniel Arturo , Calderón-Garcidueñas Ana Laura , Gama-Lizárraga Elizabeth , Enríquez-Peregrino Kevin Giuseppe , Curiel-Zamudio José María 
Published: June 2024

Background: Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. Case description: A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. Discussion: The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. Conclusion: We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement.
Quality and readability of online information and materials on post-surgery breast seroma
Authors: Bald Alexander , Richardson Harriet , Al Samaraee Ahmad , Fasih Tarannum 
Published: June 2024

Aims/Background Seroma formation is the most common complication following breast surgery. However, there is little evidence on the readability of online patient education materials on this issue. This study aimed to assess the accessibility and readability of the relevant online information. Methods This systematic review of the literature identified 37 relevant websites for further analysis. The readability of each online article was assessed through using a range of readability formulae. Results The average Flesch-Reading Ease score for all patient education materials was 53.9 (± 21.9) and the average Flesch-Kincaid reading grade level was 7.32 (± 3.1), suggesting they were ‘fairly difficult’ to read and is higher than the recommended reading level. Conclusion Online patient education materials regarding post-surgery breast seroma are at a higher-than-recommended reading grade level for the public. Improvement would allow all patients, regardless of literacy level, to access such resources to aid decision-making around undergoing breast surgery.
Exploration and evaluation of reporting quality of randomised controlled trials on blended learning in medical education
Authors: Zhang Xiaoli , Zhang Guanran , Chen Yanru , Wang Fuwu , Guo Yuji , Li Xiaorui , Zhang Jianming 
Published: June 2024

Aims/Background Blended learning has been a commonly adopted teaching mode in the medical education community in recent years. Many studies have shown that the blended learning mode is superior to the traditional teaching mode. Nonetheless, pinpointing the specific advantages provided by blended teaching methods is challenging, since multiple elements influence their effectiveness. This study aimed to investigate the reliability of the conclusions of published randomised controlled trials (RCTs) on blended learning in medical education by assessing their quality, and to provide suggestions for future related studies. Methods Two investigators searched PUBMED and EMBASE, and assessed RCTs related to medical blended learning published from January 1, 2010 to December 31, 2021. The analysis of the overall quality of each report was based on the 2010 consolidated standard of reporting trials (CONSORT) Statement applying a 28-point overall quality score. We also conducted a multivariate assessment including year of publication, region of the trial, journal, impact factor, sample size, and the primary outcome. Results A total of 22 RCTs closely relevant to medical blended learning were eventually selected for study. The results demonstrated that half of the studies failed to explicitly describe at least 34% of the items in the 2010 CONSORT Statement. Medical blended learning is an emerging new teaching mode, with 95.45% of RCTs published since 2010. However, many issues that we consider crucial were not satisfactorily addressed in the selected RCTs. Conclusion Although the 2010 CONSORT Statement was published more than a decade ago, the quality of RCTs remains unsatisfactory. Some important items were inadequately reported in many RCTs such as sample size, blinding, and concealment. We encourage researchers who focus on the effects of blended learning in medical education to incorporate the guidelines in the 2010 CONSORT Statement when designing and conducting relevant research. Researchers, reviewers, and editors also need to work together to improve the quality of relevant RCTs in accordance with the requirements of the 2010 CONSORT Statement.
Enhancing pediatric asthma management through multifaceted health education
Authors: Lin Guang-Qun , Ye Zu-Qiong , Song En-Lian , Lin Yu-Nan 
Published: June 2024

BACKGROUND
Pediatric asthma is a significant public health issue that impacts the quality of life of children globally. Traditional management approaches focus on symptom control and medication adherence but often overlook the comprehensive educational needs of patients and their families. A multifaceted health education approach may offer a more holistic strategy in managing pediatric asthma, especially in outpatient settings.
AIM
To evaluate the efficacy of a comprehensive health education strategy in improving disease management, medication adherence, and quality of life among children with asthma in outpatient settings.
METHODS
In total, 100 pediatric patients with severe asthma were enrolled from January 2021 to November 2022 and randomly allocated to a control group (n = 50) or an observation group (n = 50). The control group received standard nursing care, including basic nursing interventions and health education upon admission. In contrast, the observation group was exposed to a broad spectrum of health education methodologies, including internet-based hospital systems, social media channels, one-on-one verbal education, informational brochures, slide presentations, telephone check-ins, animated videos, and illustrated health education manuals. Data on asthma management knowledge, symptom control, quality of life [St. George’s Respiratory Questionnaire (SGRQ)], treatment adherence, and nursing satisfaction were collected and analyzed.
RESULTS
The scores of the observation group in knowledge areas, such as medication, home care, disease understanding, symptom management, prevention strategies, and nutritional guidance, were significantly higher than those of the control group (P < 0.05). In addition, the observation group exhibited greater symptom control, improved quality of life based on their SGRQ scores, and higher treatment adherence post-intervention (P < 0.05). Nursing satisfaction was also rated higher in the observation group across all evaluated areas (P < 0.05).
CONCLUSION
Implementing a diversified health education approach in pediatric asthma management significantly enhances disease understanding, symptom management, and treatment adherence, leading to improved quality of life for affected children. These findings underscore the importance of multifaceted clinical health education in augmenting disease awareness and facilitating continuous improvements in asthma control rates, highlighting the potential benefits of incorporating comprehensive educational strategies into pediatric asthma care protocols.
Adoption of network and plan-do-check-action in the international classification of disease 10 coding
Authors: Lian Biao 
Published: June 2024

BACKGROUND
with the widespread application of computer network systems in the medical field, the plan-do-check-action (PDCA) and the international classification of diseases tenth edition (ICD-10) coding system have also achieved favorable results in clinical medical record management. However, research on their combined application is relatively lacking. Objective: it was to explore the impact of network systems and PDCA management mode on ICD-10 encoding. Material and Method: a retrospective collection of 768 discharged medical records from the Medical Record Management Department of Meishan People’s Hospital was conducted. They were divided into a control group (n = 232) and an observation group (n = 536) based on whether the PDCA management mode was implemented. The two sets of coding accuracy, time spent, case completion rate, satisfaction, and other indicators were compared.
AIM
To study the adoption of network and PDCA in the ICD-10.
METHODS
A retrospective collection of 768 discharged medical records from the Medical Record Management Department of Meishan People’s Hospital was conducted. They were divided into a control group (n = 232) and an observation group (n = 536) based on whether the PDCA management mode was implemented. The two sets of coding accuracy, time spent, case completion rate, satisfaction, and other indicators were compared.
RESULTS
In the 3, 6, 12, 18, and 24 months of PDCA cycle management mode, the coding accuracy and medical record completion rate were higher, and the coding time was lower in the observation group as against the controls (P < 0.05). The satisfaction of coders (80.22% vs 53.45%) and patients (84.89% vs 51.72%) in the observation group was markedly higher as against the controls (P < 0.05).
CONCLUSION
The combination of computer networks and PDCA can improve the accuracy, efficiency, completion rate, and satisfaction of ICD-10 coding.
Effect analysis of applying high-quality service model to surgical nursing
Authors: Chen Li , Tu Qiu-Mei , Guo Zhao-Di , Zhu Xiao-Wei , Wang Wei , Xie Hui-Fang , Ye Yuan 
Published: June 2024

BACKGROUND
Surgical care of the hand plays a crucial role in the medical field, as problems with the hand can profoundly affect a patient's quality of life and function. In order to meet the needs of patients, improve patient satisfaction and improve treatment outcomes, high-quality service models have been introduced in the field of nursing.
AIM
To explore the effect analysis of applying high-quality service model to surgical nursing.
METHODS
We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022, using a quality service model that included improved patient education, pain management, care team collaboration, and effective communication. Another group of patients received traditional care as a control group. We compared postoperative recovery, satisfaction, complication rate, and length of hospital stay between the two groups. Inferential statistics were used to compare the difference between the two groups by independent sample t test, Chi-square test and other methods to evaluate the effect of intervention measures.
RESULTS
Postoperative recovery time decreased from 17.8 ± 2.3 d to 14.5 ± 2.1 d, pain score decreased from 4.7 ± 1.9 to 3.2 ± 1.4, and hand function score increased from 78.4 ± 7.1 to 88.5 ± 6.2. In terms of patient satisfaction, the quality service model group scored 87.3 ± 5.6 points, which was significantly higher than that of the traditional care group (74.6 ± 6.3 points). At the same time, patients' understanding of medical information also improved from 6.9 ± 1.4 to 8.6 ± 1.2. In terms of postoperative complications, the application of the quality service model reduced the incidence of postoperative complications from 26% to 10%, the incidence of infection from 12% to 5%, and the incidence of bleeding from 10% to 3%. The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications. In addition, the average hospital stay of patients in the quality service model group was shortened from 6.8 ± 1.5 d to 5.2 ± 1.3 d, and the hospitalization cost was also reduced from 2800 ± 600 yuan to 2500 ± 500 yuan.
CONCLUSION
Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes, including faster recovery, less pain, greater satisfaction, and reduced complication rates.