bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stage-dependent prognostic shift in mismatch repair-deficient tumors: Assessing patient outcomes in stage II and III colon cancer
Authors: Hestetun Kjersti Elvestad , Rosenlund Nina Benedikte , Stanisavljević Luka , Dahl Olav , Myklebust Mette Pernille 
Published: August 2022

IntroductionDeficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) is associated with an improved prognosis in colon cancer stage II but poor prognosis in stage IV colon cancer. The clinical significance of dMMR in colon cancer stage III is not established.MethodsTissue microarrays (TMAs) from 544 patients with colon cancer stage II and III with clinicopathological and survival data were stained for mismatch repair (MMR) proteins, CD3, CD8, and programmed death ligand-1 (PD-L1), and programmed death ligand- 1 (PD-L1). Patient outcomes were reviewed.ResultsIn stage III colon cancer, dMMR was a marker of poor disease-free survival (DFS) (Kaplan–Meier, mean survival in months: dMMR: 28.76 (95% CI 18.46–39.05) vs. pMMR 40.91 (37.20–44.63), p=0.014, multivariate Cox regression: hazard ratio (HR) 4.17 (95% CI 2.02–8.61), p&lt;0.001). In stage II colon cancer, there was a tendency toward improved DFS for dMMR patients (dMMR: 57.14 (95% CI 54.66–59.62) vs. pMMR 53.54 (95% CI 51.48–55.60), p=0.015, multivariate Cox regression HR 0.24 (95% CI 0.06-1.04), p=0.057). CD3, CD8, and PD-L1 expression was not associated with prognosis of dMMR patients. Multivariate Cox regression analysis showed a significant interaction between the MMR phenotype and stage (p=0.001).ConclusiondMMR is associated with an improved prognosis in stage II colon cancer but is no longer associated with a favorable prognosis in stage III colon cancer.
Clinical and economic impact of changing reimbursement criteria for statin treatment among patients with type 2 diabetes mellitus in South Korea
Authors: Kim Siin , Choi Kyungseon , Kim Ji-yool , Suh Hae Sun 
Published: August 2022

Aim: Patients with type 2 diabetes mellitus (T2DM) in South Korea can be reimbursed for statins if they have a low-density lipoprotein cholesterol (LDL-C) level of ≥100 mg/dL. We aimed to explore the clinical and economic benefit received by T2DM patients when easing the current criteria for statin treatment by lowering the LDL-C threshold from 100 mg/dL to 70 mg/dL.Methods: We used a static course model with a 5-year period to compare the following two scenarios in T2DM patients with no history of cardiovascular (CV) events: the current criteria covering LDL-C ≥100 mg/dL and the revised criteria covering LDL-C ≥70 mg/dL. The number of target patients was estimated based on previous Korean studies on patients with T2DM. The current mix of treatments used for T2DM and costs involving CV events were estimated using the National Health Insurance Service–National Health Screening Cohort database. The baseline CV event rates and case fatality were estimated using NHIS Customized database, including 50% patients who were prescribed atorvastatin and 100% who were not prescribed statins between 2009 and 2012 among patients with T2DM in the entire Korean population. After propensity score matching, patients with T2DM not prescribed statins were followed up until 2018 to estimate the incidence rates of coronary heart disease (CHD) and stroke. The efficacy of atorvastatin for the primary prevention of CV events in patients with T2DM was derived from a pivotal clinical trial. The outcome measures were the number of CV events prevented after the change in criteria and the consequent cost savings.Results: In South Korea, the current and revised criteria covered 2,434,379 and 3,446,149 patients with T2DM, respectively. The change in criteria resulted in the prevention of 726 CV events and cost savings of US dollars (USD) 5.5 million at the national level and USD 0.0089 per member per month in the fifth year.Conclusion: Easing the reimbursement criteria for statin treatment among patients with T2DM was associated with a reduction in CV events and their related costs; therefore, changing the reimbursement criteria is worth further consideration to mitigate the burden of CV disease.
Maca (Lepidium meyenii Walp.) on semen quality parameters: A systematic review and meta-analysis
Authors: Lee Hye Won , Lee Myeong Soo , Qu Fan , Lee Je-Won , Kim Eunseop 
Published: August 2022

Background: This study aimed to examine the evidence for the effect of Lepidium meyenii Walp. [Brassicaceae] (L. meyenii W.), known as maca, on improving semen quality.Methods: Nine databases were searched for randomized controlled trials (RCTs) that examined the parameters for improvements in semen quality, regardless of the type of L. meyenii W. The risk of bias (ROB) among the studies was evaluated according to the Cochrane ROB tool.Results: Five RCTs met all of the inclusion criteria. Three RCTs showed mixed efficacy of maca in improving semen quality parameters, including sperm concentration and sperm motility, in men experiencing infertility. The meta-analysis also failed to show the efficacy of maca in increasing the sperm concentration compared to the placebo (weighted mean difference, 2.22, 95% confidence interval −2.94 to 7.37, p = 0.4). Two other RCTs also showed mixed effects of maca on several semen quality parameters in healthy men.Conclusion: The evidence from the included studies suggests unclear effects of maca on semen quality parameters in both men experiencing infertility and healthy men. However, the total number of RCTs and the total sample size were too small to draw firm conclusions.
Pulmonary adverse events associated with hypertension in non-small cell lung cancer patients receiving PD-1/PD-L1 inhibitors
Authors: Chen Jianing , Wen Yaokai , Chu Xiangling , Liu Yuzhi , Su Chunxia 
Published: August 2022

Introduction: Non-small cell lung cancer patients have gained therapeutic benefits from immune checkpoint inhibitors, although immune-related adverse events (irAEs) could be inevitable. Whether irAEs are associated with chronic diseases is still unclear, our study aims to clarify the distinct adverse events in NSCLC patients with concomitant hypertension.Methods: Adverse event cases were searched and collected in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2015 to December 2021. We performed disproportionality analysis to detect safety signals by calculating reporting odds ratios (ROR) and corresponding 95% confidence intervals (95% CIs), information component (IC), and the lower bound of the information component 95% credibility interval (IC025).Results: Among 17,163 NSCLC patients under treatment with single-agent anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) inhibitor (nivolumab, pembrolizumab, cemiplimab, durvalumab, atezolizumab, and avelumab), 497 patients had hypertension while 16,666 patients had no hypertension. 4,283 pulmonary AEs were reported, including 166 patients with hypertension and 4,117 patients without hypertension. Compared with patients without hypertension, patients with hypertension were positively associated with increased reporting of interstitial lung disease (ROR = 3.62, 95%CI 2.68–4.89, IC = 1.54, IC025 = 0.57) among patients receiving anti-PD-1 treatment. The median duration of onset from the time of initiation of anti-PD-1 administration was 28 days (IQR, 12.00–84.25).Conclusion: Our pharmacovigilance analysis showed the profile of pulmonary toxicities in NSCLC patients with hypertension caused by anti-PD-1/PD-L1 inhibitors. Interstitial lung disease was the statistically significant reporting adverse event in patients with hypertension receiving anti-PD-1 treatment.
Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report
Authors: Clavo Bernardino , Rodríguez-Abreu Delvys , Galván Saray , Federico Mario , Martínez-Sánchez Gregorio , Ramallo-Fariña Yolanda , Antonelli Carla , Benítez Gretel , Rey-Baltar Dolores , Jorge Ignacio J , Rodríguez-Esparragón Francisco , Serrano-Aguilar Pedro 
Published: August 2022

Background: Pain secondary to chemotherapy-induced peripheral neuropathy (CIPN) can limit the administration of chemotherapy, cancer-treatment outcomes, and the quality of life of patients. Oxidative stress and inflammation are some of the key mechanisms involved in CIPN. Successful treatments for CIPN are limited. This report shows our preliminary experience using ozone treatment as a modulator of oxidative stress in chronic pain secondary to CIPN.Methods: Ozone treatment, by rectal insufflation, was administered in seven patients suffering from pain secondary to grade II or III CIPN. Pain was assessed by the visual analog scale (VAS).Results: All patients, except one, showed clinically relevant pain improvement. Median pain score according to the VAS was 7 (range: 5–8) before ozone treatment, 4 (range: 2–6) at the end of ozone treatment (p = 0.004), 5.5 (range: 1.8–6.3) 3 months after the end of ozone treatment (p = 0.008), and 6 (range: 2.6–6.6) 6 months after the end of ozone treatment (p = 0.008). The toxicity grade, according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0), improved in half of the patients.Conclusion: This report shows that most patients obtained clinically relevant and long-lasting improvement in chronic pain secondary to CIPN after treatment with ozone. These observed effects merit further research and support our ongoing randomized clinical trial (NCT04299893).
A WeChat-based self-compassion training to improve the treatment adherence of patients with schizophrenia in China: Protocol for a randomized controlled trial
Authors: Dong Die , Mu Ting-Yu , Xu Jia-Yi , Dai Jia-Ning , Zhou Zhi-Nan , Zhang Qiong-Zhi , Shen Cui-Zhen 
Published: August 2022

BackgroundAt present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated that increasing a patient’s level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia.MethodsThe protocol for the randomized controlled trial (RCT) is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline (T0), immediately after the intervention (T1), and 3 weeks after the intervention (T2). Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention (T1).Expected results:The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients’ desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries.
Analysis of sleep problem in children aged 1–3 years with autism spectrum disorder in Zhejiang province, China
Authors: Yao Dan , Wang Shasha , Li Fangfang , Gao Minjie , Shao Jie 
Published: August 2022

BackgroundHigh prevalence of sleep problems have been founded in children with Autism Spectrum Disorder (ASD), with rates ranging from 50 to 80%. We aimed to study the sleep status and the occurrence of sleep problems in children with autism spectrum disorder (ASD) aged 1–3 years, and to provide reference for guiding early comprehensive intervention for ASD children from the perspective of sleep.MethodsFrom January 1 to December 31, 2021, 74 ASD children who met the diagnostic criteria of “Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-V)” served as case group while 84 typically-developing children of the same sex and age served as control group. An original Children's Sleep Habit Questionnaire was adopted to compare the sleep status of children in the two groups and to conduct statistical analysis on related factors.ResultsThe incidence of sleep problems in the case group (78.4%) was significantly higher than that in the control group (34.5%) (P &lt; 0.001). Compared with the children in the control group, children in the case group had later bedtime (P &lt; 0.05) and less sleep duration (P &lt; 0.05), and required longer time to fall asleep (P &lt; 0.001) The incidence of sleep problems in children who could fall asleep autonomously in the case group was significantly lower than that in children who needed parental help (P &lt; 0.05). In the case group, the longer the screen exposure time, the higher the incidence of sleep problems (P &lt; 0.05).ConclusionsThe incidence of sleep problems in ASD children aged 1–3 years is also high, mainly manifested in late bedtime, difficulty falling asleep, frequent night awakenings and less sleep duration. Both sleep patterns and screen exposure can impact their sleep. In the early comprehensive intervention of ASD children, it is necessary to pay full heed to their sleep status and take timely intervention measures in order to improve the quality of life for the ASD children and their families.
Treatment providers' perspectives on a gender-responsive approach in alcohol and drug treatment for women in Belgium
Authors: Schamp Julie , Vanderplasschen Wouter , Meulewaeter Florien 
Published: August 2022

BackgroundGender inequity is a pervasive challenge to health equity on a global scale, and research shows the impact of sex and gender on substance use regarding for example epidemiology, treatment needs, treatment admission and treatment outcomes. The gender-transformative approach to action and health indicates that health interventions may maintain, exacerbate or reduce gender-related health inequalities, depending on the degree and quality of gender-responsiveness within the programme or policy. However, research shows a lack of gender-responsive initiatives in the alcohol and drug addiction field.AimsThe purpose of this study is to explore in depth how alcohol and drug treatment can be made more sensitive to female users' treatment needs from the perspective of service providers. Consequently, study findings can inform the development of gender-responsive treatment options and aid to a deeper understanding of how these trends are designated on the continuum of approaches to action and health in the alcohol and drug field.MethodsFour focus groups were organized across different regions in Belgium with a total of 43 participants, including service providers, policy makers and women who use(d) drugs.ResultsThe perspective of the participants on substance use prevention and treatment for female users incorporates some crucial gender-specific and gender-transformative features. Next to implementing mother-child options, a holistic approach, experts by experience and empowering women in treatment, professionals report the relevance of awareness raising campaigns targeting all levels and sectors in society. Also, recurring attention was given to the role of men in the narratives of female users.ConclusionStudy findings show that the field of alcohol and drug prevention and treatment is being looked at through the lens of gender-responsiveness. However, to achieve improvement in the lives of both women and men, and hence creating more equal chances and opportunities in substance abuse treatment, the gender-transformative approach in addiction care needs to be further explored, criticized and established in practice and future research.
COVID-19 related innovation in Aotearoa/New Zealand mental health helplines and telehealth providers – mapping solutions and discussing sustainability from the perspective of service providers
Authors: Pavlova Alina , Scarth Bonnie , Witt Katrina , Hetrick Sarah , Fortune Sarah 
Published: August 2022

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic and associated interventions resulted in changes in both the demand and supply of mental health services and necessitated agile adaptation and innovation from service providers.AimsThe aim of this study was to explore what innovative solutions were adopted in response to COVID-19 and the pandemic control measures, what opportunities and challenges were associated with these innovations, as well as to critically reflect on the longer-term sustainability of the innovations in the context of Aotearoa/New Zealand mental healthcare.Materials and methodsWe used thematic analysis to analyse the data from the 23 in-depth interviews with helpline employees and general practitioners from 18 service providers that regularly engage in mental healthcare.ResultsTwo key themes related to COVID-19 and the pandemic control measures were identified from respondents’ accounts. These were “Technological innovations” and “Process innovations” where providers noted types of innovative solutions, and opportunities and challenges associated with those. The themes culminated in a meta theme “Sustainability of changes to service delivery” that appeared consistently in each theme and asks to consider how sustainable these innovative solutions might be in the long-term. Namely, sustainability of innovation was questioned in respect to the (a) innovative solutions being the emergency solutions with little or no impact analysis, (b) “returning back to normal” due to limited future funding and innovation as a sunk cost, and (c) sporadic and inconsistent innovation between service providers that does not contribute to quality and continuity of care from the systems perspective.ConclusionCOVID-19 and the measures of pandemic control were associated with an increase in innovative solutions from service providers. There were both opportunities and challenges associated with these innovative efforts and the sustainability of innovation was questioned. Future research about COVID-19 related innovation of service provision should focus on service user experiences and empirically measure the innovation safety and efficacy.
Statistical investigation on equatorial pitch angle distribution of energetic electrons in Earth’s outer radiation belt during CME- and CIR-driven storms
Authors: Chakraborty S. , Chakrabarty D. , Reeves G. D. , Baker D. N. , Rae I. J. 
Published: August 2022

We present a statistical investigation (September 2012 - September 2017) of pitch angle distribution (PAD) of energetic electrons (∼30 keV - 1 MeV) in the outer radiation belt (L ≥ 3) during CME- and CIR-driven geomagnetic storms using Van Allen Probe measurements. We selected geomagnetic storms based on minimum of SYM-H being less than -50 nT and classified the storms according to their drivers. Thus, we obtained 23 CME- and 24 CIR-driven storms. During the storm intervals, pitch angle resolved electron flux measurements are obtained from the MagEIS instrument on-board Van Allen Probe-A spacecraft. We assume symmetric pitch angle distributions around 90° pitch angle and fit the observed PADs with Legendre polynomials after propagating them to the magnetic equator. Legendre coefficients c2 and c4, and the ratio R = |c2/c4| are used to categorize the different PAD types. To resolve the spatio-temporal distribution of PADs, these coefficients are binned in 5 L-shell bins, 12 MLT bins for seven energy channels and four storm phases. We found that several hundreds of keV electrons exhibit clear dependence on local time, storm phases and storm drivers, with increased anisotropy for CME-driven storms during main and early recovery phases. On the contrary, we found that tens of keV electrons do not exhibit significant dependence on these parameters. We have discussed the different physical mechanisms responsible for the observed MLT dependent PADs and found drift-shell splitting to be the major contributor.
Development and validation of a competing risk model for second primary pancreatic ductal adenocarcinoma: A population-based study
Authors: Song Lishan , Xu Chaojie , Zhang Tong , Chen Shengyang , Shi Zhigang , Hu Shuiquan , Cheng Bingbing , Tong Hao , Wei Guangkun , Li Xiaoyong 
Published: August 2022

BackgroundWith advances in early diagnosis and treatment, the number of cancer survivors continues to grow, and more and more cancer survivors face the threat of second primary cancer (SPM). Second primary pancreatic ductal adenocarcinoma (spPDAC) is an important subclass of SPM, but its prognostic characteristics are poorly understood.MethodsA total of 5,439 spPDAC samples and 67,262 primary pancreatic ductal adenocarcinoma (pPDAC) samples were extracted from the SEER database for this study. Survival differences between spPDAC and pPDAC samples were compared using Kaplan–Meier curves and log-rank tests. The Fine and Gray proportional subdistributed hazard method was used to analyze potential associations between clinical variables and pancreatic ductal adenocarcinoma-specific death (PDACSD) and death from other causes. After that, the clinical variables significantly related to PDACSD were screened out to construct a competing risk nomogram, which was used to evaluate the probability of the occurrence of PDACSD. The C-index was used to evaluate the discriminative ability of the model. The area under the curve (AUC) was used to verify the discrimination of the model. The calibration curve was used to verify the calibration of the model. Decision curve analysis (DCA) was used to validate the clinical utility of the model.ResultsCompared with patients with spPDAC, the pPDAC sample had a better prognosis (p = 0.0017). Across all spPDAC samples, the three most common sites of first-present cancer were the prostate, breast, and digestive system. Age (p &lt; 0.001), race (p = 0.006), interval (p = 0.016), location (p &lt; 0.001), T stage (p = 0.003), M stage (p &lt; 0.001), chemotherapy (p &lt; 0.001), and radiotherapy (p = 0.006) were the clinical variables associated with PDACSD screened by multivariate competing risks analysis. The concordance index values for the training and validation sets were 0.665 (95% CI, 0.655, 0.675) and 0.666 (95% CI, 0.650, 0.682), respectively. AUC, calibration curve, and DCA indicated that the model we constructed had good discrimination, calibration, and clinical utility.ConclusionsIn conclusion, we first analyzed the impact of previous cancer history on prognosis. We then constructed a competing risk model that can predict the probability of developing PDACSD in spPDAC. This model has good discriminative ability, calibration, and clinical practicability and has certain guiding value for clinical decision-making.