bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma
Authors: Cui Jiujie , Yang Haiyan , Liu Jue , Chen Donghui , Hu Jiong , Zhang Haiyan , Wang Yu , Han Ting , Mao Tiebo , Jiao Feng , Biskup Ewelina , Pan Yaotian , Liu Min , Wang Liwei 
Published: June 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.

Methods
In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).

Results
Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.

Conclusions
K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted.

Trial registration
NCT02720666. Registered 28 Match 2016 - Retrospectively registered.
REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer
Authors: Nakajima Hiromichi , Kotani Daisuke , Bando Hideaki , Kato Takeshi , Oki Eiji , Shinozaki Eiji , Sunakawa Yu , Yamazaki Kentaro , Yuki Satoshi , Nakamura Yoshiaki , Yamanaka Takeharu , Yoshino Takayuki , Ohta Takashi , Taniguchi Hiroya , Kagawa Yoshinori 
Published: June 2021

Abstract
Background
Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses of clinical trials has suggested that RAS status in circulating tumor DNA (ctDNA) has a high probability to select patients who could benefit from anti-EGFR mAb rechallenge.

Methods
This trial is composed of 2 phases: a monitoring phase (REMARRY) and a trial phase (PURSUIT). A monitoring phase, the REMARRY study, aims to evaluate the dynamics of plasma RAS status during the subsequent treatments after refractory to anti-EGFR therapy in patients with mCRC with RAS/BRAF V600E wild-type tumors who have progressed after a response to previous anti-EGFR therapy, using a highly sensitive digital polymerase chain reaction OncoBEAM RAS CRC kit in a central laboratory (Sysmex, Japan). A trial phase, the PURSUIT trial, is a multicenter, single-arm phase II trial to assess the efficacy and safety of rechallenge therapy with panitumumab plus irinotecan in patients without RAS mutations in ctDNA (plasma RAS negative) in the REMARRY study. Key eligibility criteria of the PURSUIT trial include RAS/BRAF V600E wild-type mCRC in tumor tissue refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; progression after complete or partial response to previous anti-EGFR therapy; plasma RAS negative (defined as plasma mutant allele frequencies [MAF] of all RAS ≤ 0.1%) within 28 days prior to enrollment; 4 months or more between the last administration of previous anti-EGFR mAb and the start of protocol treatment; and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1. The primary endpoint is the confirmed objective response rate (ORR). The target sample size of the PURSUIT trial is 50 patients. Biomarker analyses will be performed in parallel using the OncoBEAM RAS CRC kit and a next-generation sequencing-based ctDNA analysis (Guardant360).

Discussion
Our trial aims to confirm the clinical benefit of anti-EGFR mAb rechallenge therapy in patients with plasma RAS negative. Moreover, through biomarker analyses, our trial will shed light on which patients would benefit from rechallenge in addition to being plasma RAS negative.

Trial registration
The REMARRY study: UMIN, UMIN000036424. Registered date: April 5, 2019. The PURSUIT trial: jRCT, jRCTs031190096. Registered date: October 1, 2019.
Cancer-specific survival by stage of bladder cancer and factors collected by Mallorca Cancer Registry associated to survival
Authors: Ripoll J. , Ramos M. , Montaño J. , Pons J. , Ameijide A. , Franch P. 
Published: June 2021

Abstract
Background
Information about survival by stage in bladder cancer is scarce, as well as about survival of non-invasive bladder cancer. The aims of this study are: 1) to find out the distribution of bladder cancer by stage; 2) to determine cancer-specific survival by stage of bladder cancer; 3) to identify factors that explain and predict the likelihood of survival and the risk of dying from these cancers.

Methods
Incident bladder cancer cases diagnosed between 2006 and 2011 were identified through the Mallorca Cancer Registry. Inclusion criteria: cases with code C67 according to the ICD-O 3rd edition with any behaviour and any histology, except lymphomas and small cell carcinomas. Cases identified exclusively through the death certificate were excluded. We collected the following data: sex; age; date and method of diagnosis; histology according to the ICD-O 3rd edition; T, N, M and stage at the time of diagnosis; and date of follow-up or death. End point of follow-up was 31 December 2015. Multiple imputation (MI) was performed to estimate cases with unknown stage. Cases with benign or indeterminate behaviour were excluded for the survival analysis. Actuarial and Kaplan-Meier methods and Cox regression models were used for survival analysis.

Results
One thousand nine hundred fourteen cases were identified. 14% were women and 65.4% were 65 years or older. 3.9% had no stage (benign or undetermined behaviour) and 11.5% had unknown stage. After MI, 37.5% were in stage Ta (non-invasive papillary carcinoma), 3.2% in stage Tis (carcinoma in situ), 34.3% in stage I, 11.7% in Stage II, 4.3% in stage III, and 9.0% in stage IV. Survival was 76% at 5 years. Survival by stage: 98% at stage Ta, 90% at stage Tis, 85% at stage I, 45% at stage II, 35% at stage III, and 7% at stage IV. The Cox model showed that age, histology, and stage, but not sex, were associated with survival.

Conclusion
Bladder cancer survival vary greatly with stage, among both non-invasive and invasive cases. The percentage of non-invasive cancers is high. Stage, age, and histology are associated to survival.
Prevalence and influencing factors of chronic post-traumatic stress disorder in patients with myocardial infarction, transient ischemic attack (TIA) and stroke – an exploratory, descriptive study
Authors: Dollenberg Aurora , Moeller Sebastian , Lücke Caroline , Wang Ruihao , Lam Alexandra P. , Philipsen Alexandra , Gschossmann Jürgen M. , Hoffmann Falk , Müller Helge H. O. 
Published: June 2021

Abstract
Background
Cardio- and cerebrovascular events such as myocardial infarction (MI), stroke and transient ischemic attack (TIA) are leading causes of death and disability and have also been associated with poor mental outcomes. In addition, cardio- and cerebrovascular events may pose the risk of experiencing a sudden traumatic occurrence of symptoms during ictus and thus contribute to high rates of PTSD as well as high rates of subsequent depression and anxiety. Moreover, MI, TIA and stroke survivors with PTSD, depressive and anxiety symptoms may have poorer health-related quality of life (HRQoL) and poorer disease prognosis than patients who do not develop psychiatric symptoms after ictus. However, data on the prevalence of PTSD, anxiety and depression, as well as the HRQoL, coping strategies and potential risk factors for development of PTSD in these patients, are rare.

Methods
In an exploratory, descriptive study we interviewed 112 patients (54 MI, 18 TIA, 40 stroke; mean age: 69.5 years, 55.4% males) from three general physician practices and used psychometric self-assessment tools to determine the occurrence of PTSD and psychosomatic comorbidity, anxiety and depression and to assess HRQoL and coping strategies. We evaluated disease severity and compared the patient groups to each other. Moreover, we assessed psychological outcome differences between patients with or without PTSD after ictus.

Results
The prevalence of PTSD after MI, TIA and stroke was 23.2%. The patients who developed PTSD had higher rates of depression, anxiety and maladaptive coping as well as reduced HRQoL. Adaptive coping was positively related to better mental HRQoL and negatively related to anxiety and depression. Disease severity of MI, TIA and stroke was not related to PTSD, depression, anxiety or physical HRQoL.

Conclusions
Experiencing MI, TIA or stroke means confronting a life-threatening event for those affected and, therefore, these can be regarded as traumatic events. Cerebral and cardiovascular events increase the risk of developing chronic PTSD with subsequent increased depression and anxiety and reduced HRQoL. These findings emphasize the need for early screening and diagnosis of PTSD in somatically ill patients, which should be followed by specialized treatment, as PTSD hampers overall (somatic) disease prognosis.

Trial registration
German Clinical Trials Register, DRKS00021730, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021730, registered 05/19/2020 - Retrospectively registered.
Stroke and cardiovascular risk factors among working-aged Finnish migraineurs
Authors: Sumelahti Marja-Liisa , Sumanen Merika S. , Mattila Kari J. , Sillanmäki Lauri , Sumanen Markku 
Published: June 2021

Abstract
Background
The aim of our study was to evaluate the risk for comorbid cardio- and cerebrovascular diseases in the working-aged migraine population of Finland.

Methods
A total of 1505 cases who reported diagnosed migraine and 3010 controls from a cohort of 11,596 cases in the Finnish Health and Social Support Study were included. The study material was linked with two registers. ICD diagnoses I63 for ischemic stroke (IS), I21 − I22 for acute myocardial infarction (AMI), and G43 for transient ischemic attack (TIA) among study participants were drawn from the national Finnish Care Register for Health Care at the follow-up in 2012. Reimbursed triptan prescriptions were drawn from the national Social Security Institution (SII) data. The self-reported vascular risk factors were hypertension, high cholesterol values, any diabetes, myocardial infarction, stroke, and TIA. Odds Ratios (OR) with 95% confidence (95% CI) intervals were assessed for diagnosed stroke, myocardial infarction, and TIA.

Results
Migraineurs were mostly female (82%) and ≥ 54 years old (62%). Triptans were reimbursed among 34.7% of migraineurs. A self-reported hypertension (21%), high serum cholesterol (38%), and any diabetes (7%) were more common among migraineurs vs controls (p < 0.05). There was no risk for AMI. The risk for TIA (OR 3.20, 95% CI 1.45–7.05) and IS (2.57, 95% CI 1.28–5.17) among migraineurs vs controls remained high after adjustment for self-reported hypertension, obesity, and smoking. The risk was higher among women in two groups ≥54 years (3.25, 95% CI 1.35–7.84 and 5.0, 95% CI 1.94–12.89, respectively). The average age for IS in migraine was 57.5 years and for TIA 58.2 years among women, and 52.8 years and 50.3 years among men, respectively.

Conclusion
Cardiovascular risk should be screened in the aging migraine population, and hormonal and other migraine-related risk factors should be considered, especially among women. Efficacious attack treatment with triptans should be offered to migraine patients who do not show contraindications.
Estimating exposure to neighborhood crime by race and ethnicity for public health research
Authors: Lodge Evans K. , Hoyo Cathrine , Gutierrez Carmen M. , Rappazzo Kristen M. , Emch Michael E. , Martin Chantel L. 
Published: June 2021

AbstractBackgroundPolice-reported crime data (hereafter “crime”) is routinely used as a psychosocial stressor in public health research, yet few studies have jointly examined (a) differences in crime exposure based on participant race and ethnicity, (b) differences in measures of crime exposure, and (c) considerations for how exposure to police is captured in police-recorded crime data. We estimate neighborhood exposure to crime and discuss the implications of structural differences in exposure to crime and police based on race and ethnicity.MethodsUsing GPS coordinates from 1188 participants in the Newborn Epigenetics Study, we estimated gestational exposure to crime provided by the Durham, North Carolina, Police Department within (a) 800 m and (b) the Census block group of residence. We controlled for non-overlapping spatial boundaries in crime, Census, residential, and police data to report crime spatial (crime per km2) and population (crime per 1000 people per km2) density.ResultsWe demonstrate dramatic disparities in exposure to crime based on participant race and ethnicity and highlight variability in these disparities based on the type of crime and crime measurement method chosen.ConclusionsPublic health researchers should give thoughtful consideration when using police-reported crime data to measure and model exposure to crime in the United States, as police-reported data encompasses joint exposure to police and crime in the neighborhood setting.
Sexual health norms and communication patterns within the close social networks of men who have sex with men and transgender women in Lima, Peru: a 2017 cross-sectional study
Authors: Ayer Amrita , Segura Eddy R. , Perez-Brumer Amaya , Chavez-Gomez Susan , Fernandez Rosario , Gutierrez Jessica , Suárez Karla , Lake Jordan E. , Clark Jesse L. , Cabello Robinson 
Published: June 2021

Abstract
Background
Social networks, norms, and discussions about sexual health may inform sexual practices, influencing risk of human immunodeficiency virus (HIV) or sexually transmitted infection (STI) acquisition. To better understand social networks of Peruvian men who have sex with men (MSM) and transgender women (trans women), we examined key social network members (SNMs), participant perceptions of these network members’ opinions toward sexual health behaviors, and associations between network member characteristics and condomless anal intercourse (CAI).

Methods
In a 2017 cross-sectional study, a convenience sample of 565 MSM and trans women with HIV-negative or unknown serostatus was asked to identify three close SNMs; describe discussions about HIV and STI prevention with each; and report perceived opinions of condom use, HIV/STI testing, and partner notification of STIs. Generalized estimating equations evaluated relationships between SNM characteristics, opinions, and discussions and participant-reported CAI.

Results
Among participants who identified as MSM, 42.3% of key SNMs were perceived to identify as gay. MSM “never” discussed HIV and STI prevention concerns with 42.4% of heterosexual SNMs, but discussed them “at least once weekly” with 16.9 and 16.6% of gay- and bisexual- identifying SNMs, respectively. Among participants who identified as trans women, 28.2% of key SNMs were perceived as heterosexual; 25.9%, as bisexual; 24.7%, as transgender; and 21.2%, as gay. Trans women discussed HIV/STI prevention least with cis-gender heterosexual network members (40.2% “never”) and most with transgender network members (27.1% “at least once weekly”). Participants perceived most of their close social network to be completely in favor of condom use (71.2% MSM SNMs, 61.5% trans women SNMs) and HIV/STI testing (73.1% MSM SNMs, 75.6% trans women SNMs), but described less support for partner STI notification (33.4% MSM SNMs, 37.4% trans women SNMs). Most participants reported CAI with at least one of their past three sexual partners (77.5% MSM, 62.8% trans women). SNM characteristics were not significantly associated with participant-reported frequency of CAI.

Conclusions
Findings compare social support, perceived social norms, and discussion patterns of Peruvian MSM and trans women, offering insight into social contexts and sexual behaviors.

Trial registration
The parent study from which this analysis was derived was registered at ClinicalTrials.gov (Identifier: NCT03010020) on January 4, 2017.
Lumbar Scheuermann’s disease found in a patient with osteogenesis imperfecta (OI) caused by a heterozygous mutation in COL1A2 (c.4048G > A): a case report
Authors: Wang Shiwei , Wang Xiaoli , Teng Xiaochun , Li Songbai , Zhang Hanyi , Shan Zhongyan , Li Yushu 
Published: June 2021

Abstract
Background
Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann’s disease is an atypical type of Scheuermann’s disease accompanied by Schmorl’s nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann’s disease is unclear, genetic and environmental factors are likely.

Case presentation
Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl’s nodes.

Conclusions
This is the first reported case of OI coexisting with the spinal presentation of Scheuermann’s disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann’s disease. In conclusion, this case demonstrates the relationship between Scheuermann’s disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.
A qualitative exploration of the unmet information needs of Chinese advanced cancer patients and their informal caregivers
Authors: Wang Tao , Molassiotis Alex , Chung Betty Pui Man , Zheng Si-Lin , Huang Hou-Qiang , Tan Jing-Yu 
Published: June 2021

Abstract
Background
Studies in the West have demonstrated that appropriate informational support is a vital component of cancer care, with positive effects on both patients and their informal caregivers. Since little is known about the information needs of advanced cancer patients and informal caregivers in China, where ‘silence as virtue’ is much more valued and the communication style is less open, this study was therefore conducted to elaborate the information needs of advanced cancer patients and informal caregivers as well as to explore their perceptions and experiences regarding their unmet information needs in the Chinese context.

Methods
This sub-study of a previous cross-sectional survey utilized a qualitative descriptive study design. The approach involved semi-structured interviews that followed an interview guide to collect data. Eligible participants were the advanced cancer patients and informal caregivers who had participated in the previous cross-sectional survey and reported unmet information needs. Each interview was audio-recorded and transcribed verbatim. Descriptive content analysis was used to analyze the data.

Results
Seventeen advanced cancer patients and 15 informal caregivers with unmet information needs participated in the semi-structured interviews, with ages ranging from 32 to 63 years old for patients and from 32 to 70 for informal caregivers. Four categories were extracted from the interviews with the patients and caregivers: (1) types of unmet information needs; (2) reasons for information needs not being met; (3) preferences for the provision of information; and (4) meaning and role of information. Each category had two to four sub-categories for both the patients and the caregivers, which were similar but not completely the same.

Conclusion
The findings indicated that the provision of appropriate information could promote informed decision-making and greater satisfaction with treatment options, reductions in psychological disturbances, and enhanced confidence and ability in self-management and capacity in caregiving. Moreover, information on Traditional Chinese Medicine and food therapy should be increased, particularly for patients at the follow-up stage, while the amount of information on prognosis should be flexible as it could increase patients’ and caregivers’ psychological burden. Healthcare professionals were the most preferred information provider, although their heavy workload resulted in time constraints. In this case, they should provide information to patients and caregivers together as a ‘whole unit.’ At the same time, the value of separate conversations should also be recognized as some caregivers preferred to conceal unpleasant information from the patient.
Feasibility, acceptability and effect of the Mindful Practice curriculum in postgraduate training of general practitioners
Authors: Villarreal Manuel , Hanson Petra , Clarke Amy , Khan Majid , Dale Jeremy 
Published: June 2021

AbstractBackgroundEarly career general practitioners are known to be at high risk of burnout. There is a need for widely applicable, cost-effective evidence-based interventions to develop trainees’ protective skills and strategies.ResultsOf 120 eligible trainees, 23 (19.2%) expressed interest in participating, 17 subsequently started the course, and 15 completed at least 5 out of its 6 sessions. All psychological measures were stable for the six-week period prior to commencing the course. Following the course, there were statistically significant (p < 0.05) improvements in wellbeing, resilience, mindfulness, emotional exhaustion, disengagement, and stress scores. Participants described numerous benefits, and most stated that they would recommend it to colleagues.ConclusionIncluding mindful practice within general practice vocational training is feasible, and in this study it benefited the psychological wellbeing of participants. Further research is needed to explore ways of increasing uptake and course completion, the sustainability of its effects, and the wider applicability of this approach.