bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant checkpoint inhibitor immunotherapy for resectable mucosal melanoma
Authors: Ho Joel , Mattei Jane , Tetzlaff Michael , Williams Michelle D. , Davies Michael A. , Diab Adi , Oliva Isabella C. Glitza , McQuade Jennifer , Patel Sapna P. , Tawbi Hussein , Wong Michael K. , Fisher Sarah B. , Hanna Ehab , Keung Emily Z. , Ross Merrick , Weiser Roi , Su Shirley Y. , Frumovitz Michael , Meyer Larissa A. , Jazaeri Amir , Pettaway Curtis A. , Guadagnolo B. Ashleigh , Bishop Andrew J. , Mitra Devarati , Farooqi Ahsan , Bassett Roland , Faria Silvana , Nagarajan Priyadharsini , Amaria Rodabe N. 
Published: October 2022

BackgroundNeoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.MethodUnder an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities.ResultsWe identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients.ConclusionNeoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.
Elevated serum neutrophil-lymphocyte ratio is associated with worse long-term survival in patients with HBV-related intrahepatic cholangiocarcinoma undergoing resection
Authors: Liu Jianwei , Xia Yong , Xue Feng , Lu Caixia , Wang Jie , Wang Chunyan , Wu Yeye , Bai Shilei , Shen Feng , Wang Kui 
Published: October 2022

BackgroundThis study aimed to examine the influence of serum inflammatory marker levels on long-term outcomes after liver resection in patients with intrahepatic cholangiocarcinoma (ICC).MethodsData from 1189 consecutive ICC patients who underwent liver resection were reviewed. The serum neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were measured before surgery. Overall survival (OS) and tumour recurrence were analysed using the Kaplan–Meier method and compared using the log-rank test. Independent risk factors for OS and tumour recurrence were analysed using the Cox hazard regression model.ResultsWe identified elevated serum NLR (≥ 2.15) as an independent risk factor for both OS and tumour recurrence (hazard ratio [HR]: 1.327, 95% confidence interval [CI]: 1.105-1.593; HR: 1.274, 95% CI: 1.074-1.510) among the three inflammatory markers assessed. Elevated NLR was associated with higher carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels, larger tumour size, multiple tumours, lymph node metastasis, vascular invasion, and more advanced tumour node metastasis (TNM) stage (III/IV). Subgroup analysis showed that elevated NLR was an independent risk factor for OS and tumour recurrence in patients with hepatitis B virus (HBV) infection compared with patients without HBV infection (HR: 1.347, 95% CI: 1.073-1.690; HR: 1.386, 95% CI: 1.112-1.726).ConclusionsElevated serum NLR was associated with worse prognosis among ICC patients who underwent liver resection, especially in patients with HBV infection.
Secondary mutant ALK-I1171s in pituitary metastases from a patient with ALK fusion-positive advanced lung adenocarcinoma: A case report and literature review
Authors: Han Dan , Zhao Kewei , Yang Qin , Zhang Liling , Fei Shihong 
Published: October 2022

BackgroundPituitary metastasis accounts for a very low percentage of cases of brain metastasis from lung cancer, and there are uncertainties and challenges in diagnosis and treatment. We hope to shed some light on the diagnosis and treatment by reporting a case of ALK fusion mutation-positive lung cancer pituitary metastasis.Case presentationWe report a 48-year-old female patient with an initial diagnosis of stage IVB lung adenocarcinoma with ALK fusion. The patient developed headache, dizziness, hypopituitarism and hyperprolactinemia one year after treatment with crizotinib. Later, the patient underwent neurosurgical resection of the pituitary tumor and then symptomatic relief. Postoperative pathology suggested pituitary metastasis, and the next-generation gene sequencing conducted on the pituitary metastasis indicated that secondary drug resistance mutation ALK-I1171s occurred after the ALK fusion gene.ConclusionIn this article, we present a patient with suspected pituitary metastases with lung cancer. The progression to pituitary mass resection and next-generation gene sequencing of the pituitary metastasis are suggestive for further diagnosis and treatment.
Osimertinib versus platinum-pemetrexed in patients with previously treated EGFR T790M advanced non-small cell lung cancer: An updated AURA3 trial-based cost-effectiveness analysis
Authors: Shi Yin , Pei Rui , Liu Shao 
Published: October 2022

BackgroundA recently overall survival (OS) analysis from the AURA3 trial indicated that osimertinib improves median OS versus platinum-pemetrexed for patients with previously treated epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC). Here, we assessed the cost-effectiveness of second-line osimertinib versus platinum-pemetrexed, from the perspectives of the United States payer and the Chinese health care system.MethodsA Markov model was constructed to compare the costs and health outcomes of osimertinib versus platinum-pemetrexed in second-line treatment of EGFR T790M advanced NSCLC. Life years (LYs), quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were calculated. One-way and probabilistic sensitivity analyses assessed the robustness of the model. Cost-effectiveness was examined in the intention-to-treat (ITT) population and central nervous system (CNS) metastases population.ResultsIn the United States, compared with platinum-pemetrexed, osimertinib yielded additional effectiveness of 0.43 QALYs and -0.12 QALYs, with incremental costs of $67,588 and $16,465 in the ITT population and CNS metastases population, respectively. The ICERs of osimertinib over platinum-pemetrexed were $159,126/QALY and $-130,830/QALY, respectively. The probability of osimertinib being cost-effective was 37% and 5.76%, respectively, at the willingness-to-pay (WTP) threshold of $150,000/QALY. In China, osimertinib showed incremental effectiveness of 0.34 QALYs and -0.14 QALYs, with incremental costs of $1,663 and $-505, resulting in ICERs of $4,950/QALY and $3,754/QALY in the ITT population and CNS metastases population, respectively. At the WTP threshold of $37,489/QALY, there was a 100% and 26% likelihood that osimertinib was cost-effective in the ITT population and CNS metastases population.ConclusionIn the United States, second-line osimertinib treatment for EGFR T790M advanced NSCLC is not cost-effective compared to platinum-pemetrexed under the current WTP threshold. When the osimertinib price reduces, the economic outcome may become favorable. In China, assuming a WTP threshold of $37,489/QALY, osimertinib is the dominant treatment strategy compared with platinum-pemetrexed in the ITT population and provides cost savings for CNS metastases patients.
Positive short term effects of an integrative korean medicine treatment package for low back pain caused by motor vehicle accidents: A retrospective chart review of real – world practice data
Authors: Park Hye-Rin , Lee Seungmin Kathy , Yoon Sang-Hoon , Jo Hee-Geun , Kim Ji-Yong , Kim Hyunho , Sul Jae-Uk , Leem Jungtae 
Published: October 2022

Backgrounds No standard treatment exist for reducing symptoms related to sequelae of motor vehicle accidents (MVAs). In Korea, comprehensive Korean Medicine (KM) treatment that includes botanical drugs (herbal medicine), acupuncture, pharmacopuncture, tuina, moxibustion, and cupping is covered by automobile insurance and increasingly used to help alleviate such pain. This study aimed to analyze real-world data and to evaluate the effectiveness and safety of comprehensive KM treatment for low back pain caused by MVAs.Methods We conducted a retrospective chart review of patients who received KM treatment during hospitalization. Records that lacked follow-up outcome assessments were excluded. The Verbal Numerical Rating Scale (VNRS), the Korean version of the Oswestry Disability Index (K-ODI) and the Korean version of the Roland-Morris Disability Questionnaire (K-RMDQ) were evaluated at admission and discharge. Adverse events were also analyzed. A paired t-test was used to identify the effectiveness of KM treatment.Results A total of 50 patients, 30 males and 20 females, were included in the analysis. The mean age of the patients was 40.72 ± 13.31 years and the average treatment period was 7.22 ± 3.84 days. After treatment, VNRS, K-ODI and K-RMDQ were significantly improved (p &lt; 0.001). There was a decrease from 5.06 ± 1.60 to 3.40 ± 1.81 in VNRS, 33.38 ± 16.88 to 24.54 ± 13.63 in K-ODI, and 6.84 ± 6.27 to 4.14 ± 4.38 in K-RMDQ. During this period, a total of two adverse events were reported.Discussion Although this retrospective chart review looked into the short term effects only, comprehensive KM treatment might be an effective and safe therapeutic option to reduce acute low back pain especially after MVA. Prospective research data is needed to support this hypothesis.
Patient-reported outcomes labeling for oncology drugs: Multidisciplinary perspectives on current status and future directions
Authors: Cella David , Chen Chieh-I , Quek Ruben G. W. , Uribarren Ainhoa , Reaney Matthew , Mastey Vera , Collyar Deborah , Chassany Olivier 
Published: October 2022

Introduction: Regulatory agencies encourage the incorporation of the patient voices throughout clinical drug development. Patient-Reported Outcomes (PROs) offer one way of doing this and their use has markedly increased in many therapeutic areas, particularly oncology, in recent years. However, few oncology drug labels include PRO data and those which do, offer little consistency.Objective: To provide multidisciplinary perspectives (patient, pharmaceutical industry, PRO researcher, regulatory expert) on PRO data in oncology drug labels.Methods: PRO data in the labels of drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for oncology indications between 2010 and 2020 were critically reviewed by authors who provided their insights on the advantages and disadvantages/gaps.Results: Forty-six oncology drugs included PRO data in their labels. Differences were observed between FDA and EMA PRO labeling (e.g., PRO concept, use of tables and graphs to display PROs or reference to clinical meaningfulness). In providing their perspectives on the number and nature of PROs in labels, authors noted limitations including: the low proportion of oncology drugs with PRO labeling, limited PRO information in labels, lack of patient-friendly language, and potential bias towards positive outcomes. Lack of consistency within- and between-agencies was noted.Conclusion: Despite regulatory agencies’ commitment to incorporate patient voices in regulatory decisions, availability of PRO information is limited in oncology drug labels. While several PRO guidance documents are available from regulatory and Health Technology Assessment agencies, harmonization of PRO guidance for labeling inclusion around the world is needed to better inform prescribers and consequently their patients in the process of shared medical decisions.
Sphingomyelin synthase 2 is a positive regulator of the CSF1R-STAT3 pathway in pancreatic cancer-associated macrophage
Authors: He Shuhua , Gu Xiang , Yang Jintong , Xu Fei , Hu Jiachun , Wang Wei , Huang Yiheng , Lou Bin , Ding Tingbo , Zhou Lu , Ye Deyong , Yu Ker , Dong Jibin 
Published: October 2022

Background: Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the pancreatic cancer stroma and are related to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC) patients. Therefore, targeting tumor-associated macrophages is a possible strategy for the treatment of pancreatic cancer.Purpose: We would like to investigate the role of sphingomyelin synthase 2 (SMS2) and the effect of the synthase 2 selective inhibitor YE2 in TAMs and the pancreatic tumor microenvironment. In addition, we also would like to investigate the mechanism by which YE2 attenuates macrophage M2 polarization.Methods: YE2 was utilized to treat macrophages (in vitro) and mice (in vivo). Western blotting and real-time PCR were used to detect the protein levels and mRNA levels of macrophage M2 polarization markers and their downstream signaling pathways. Sphingomyelin synthase 2 gene knockout (KO) mice and their controls were used to establish a PANC-02 orthotopic pancreatic cancer model, and immune cell infiltration in the tumor tissue was analyzed by immunohistochemistry (IHC).Results: We found that sphingomyelin synthase 2 mRNA expression is positively correlated with tumor-associated macrophages, the immunosuppressive microenvironment, and poor prognosis in pancreatic ductal adenocarcinoma patients. Sphingomyelin synthase 2 deficiency was confirmed to have an inhibitory effect on the growth of orthotopic PANC-02 tumors in vivo. The deficiency not only reduced the infiltration of tumor-associated macrophages but also regulated other immune components in the tumor microenvironment. In tissue culture, YE2 inhibited M2 polarization in both bone marrow-derived macrophages (BMDMs) and THP-1 macrophages and eliminated the protumor effect of M2 macrophages. In the mouse model, YE2 treatment reduced the infiltration of TAMs and regulated other immune components in the tumor microenvironment, slowing the progression of PANC-02 tumors. In terms of mechanism, we found that the inhibition of sphingomyelin synthase 2 could downregulate the expression of IL4Rα and CSF1R, thereby attenuating M2 polarization.Conclusion: The sphingomyelin synthase 2 inhibitor YE2 or sphingomyelin synthase 2 deficiency can prevent macrophage M2 polarization in pancreatic cancer, and sphingomyelin synthase 2 could be a new potential target for the treatment of pancreatic cancer.
Age and gender differences in static and dynamic balance of Chinese preschool children
Authors: Li Ruiyuan , Liu Meng , Zhu Jiefeng , Li Ruiqin , Zhao Huan , Zhang Liqing 
Published: October 2022

Objectives: Balance is a crucial ability of early age, but there is conflicting evidence with regard to age and gender differences in preschool children’s balance ability. Additionally, there are several tools available to measure balance, yet, wide variation in their use has restricted the capacity to synthesize the reference values. Therefore, the primary purpose of this study was to investigate the balance ability of preschool-aged children and determine how it is moderated by age and gender. The analysis pertained to determining whether different testing methods affect the results of static or dynamic balancing ability to provide a basis for normative balance ability data for healthy boys and girls between 3 and 6 years of age.Method: Six hundred and nineteen preschool children (296 boys and 323 girls) aged 3–6 years participated in the study. The static balance (SB) was assessed with children standing on one leg (OST) and in a tandem stance (TS) with respect to time. The balance beam test (BBT) and functional reach test (FRT) were used to evaluate dynamic balance (DB) by measuring the time spent and the distance reached, respectively.Result: The results revealed significant differences in OST with respect to gender (η2 = 0.037, p &lt; 0.001), TS (η2 = 0.026, p &lt; 0.001) and FRT (η2 = 0.016, p = 0.002); the girls performed better than boys on most balance tests except on BBT (η2 = 0.000, p = 0.596). Age had positive effects on the static and dynamic balance performance on the OST (η2 = 0.336, p &lt; 0.001), TS (η2 = 0.205, p &lt; 0.001), BBT (η2 = 0.367, p &lt; 0.001) and FRT (η2 = 0.392, p &lt; 0.001). Older children performed better than their younger counterparts. No significant interactions between age groups and sex were found.Conclusion: This study revealed that static and dynamic balance stability in preschool-aged children was affected by gender and age. Gender dimorphism is present in preschool children, older girls displayed better postural stability than boys, and balance performance improved with age. In addition, the study provides age- and gender-specific balance performance reference values for preschool children across multiple methods, which can be used to monitor static and dynamic balance development.
Changes in health behaviors and conditions during COVID-19 pandemic strict campus lockdown among Chinese university students
Authors: Zhang Boyi , Lei Si Man , Le Shenglong , Gong Qiang , Cheng Sulin , Wang Xiuqiang 
Published: October 2022

ObjectiveTo explore how a stringent campus lockdown affects the physical activity (PA), sleep and mental health of Chinese university students living in student dormitories during the COVID-19 pandemic.MethodsData on PA, sleep and mental health were collected between 24 March and 4 April 2022 from 2084 university students (mean age = 22.4 years, 61.1% male students) via an online questionnaire distributed by the students’ advisers of each dormitory. The Chinese short version of the International Physical Activity Questionnaire (IPAQ-C), Athens Insomnia Scale (CAIS) and General Health Questionnaire 12-item (GHQ-12) were applied. The Mann–Whitney test and Kruskal-Wallis tests were used to evaluate the PA profile differences between genders, before and during the lockdown period and between students’ living environments. Chi-squared (χ2) or Fisher’s exact test was used to assess changes in health behaviors by gender and students’ living environment compared to before the lockdown. A mediation model was used to examine whether sleep disorder mediated the relationship between PA and mental health in different students’ living environments.ResultsParticipants reported a significant decrease in weekly total PA levels (63.9%). Mean daily sedentary time increased by 21.4% and daily lying time increased by 10.7% compared to before lockdown. Among the participants, 21.2% had experienced insomnia, and 39.0% reported having high mental distress. Female students reported 10% higher rates of sleep disorders than male students (p &lt; 0.001), and also experienced a higher incidence of mental disorders (p &lt; 0.001). Students living with three roommates had a larger decrease in frequencies and durations of participation in light PA than other students (p &lt; 0.001). PA was negatively associated with sleep and mental health, and sleep disorder was a mediating factor between PA and mental health in the students living with two and three roommates.ConclusionThis study showed that strict lockdowns within university dormitories during the COVID-19 pandemic had a negative effect on the health of university students by changing their health behaviors, physical activity and sleep. Our findings indicate a need for strategies to promote an active lifestyle for students in space-limited dormitories in order to maintain health during a prolonged lockdown.
Media use and organ donation willingness: A latent profile analysis from Chinese residents
Authors: Gong Fangmin , Jia Yuhan , Zhang Jinzi , Cao Meiling , Jia Xiaocen , Sun Xinying , Wu Yibo 
Published: October 2022

BackgroundPrevious studies have paid attention to media as an important channel for understanding organ donation knowledge and have not divided groups according to the degree of media use to study their differences in organ donation. Therefore, the purpose of this study is to explore the influence of media use on organ donation willingness and the influencing factors of organ donation willingness of people with different media use levels.MethodsA cross-sectional study of residents from 120 cities in China was conducted by questionnaire survey. Using Mplus 8.3 software, the latent profile analysis of seven media usage related items was made, and multiple linear regression was performed to analyze the influence of varying levels of media use on organ donation willingness of different population.ResultsAll the interviewees were divided into three groups, namely, “Occluded media use” (9.7%), “Ordinary media use” (67.1%) and “High-frequency media use” (23.2%). Compared with ordinary media use, high-frequency media population (β = 0.06, P &lt; 0.001) were positively correlated with their willingness to accept organ donation, residents who used media occlusion (β = −0.02, P &lt; 0.001) were negatively correlated with their willingness to accept organ donation. The influencing factors of residents' accept willingness to organ donation were different among the types of occluded media use, ordinary media use and high-frequency media use.ConclusionIt is necessary to formulate personalized and targeted dissemination strategies of organ donation health information for different media users.