bluuebunny/crossref_metadata_2025_split huggingface dataset:
The school education, ritual customs, and reciprocity associated with self-regulating hand hygiene practices during COVID-19 in Japan
Authors: Lee Sun Youn , Sasaki Shusaku , Kurokawa Hirofumi , Ohtake Fumio 
Published: September 2022

Abstract
Background
The role of social ties, other-regarding preferences, and cultural traits in boosting community resilience and minimizing citizens’ vulnerability to crises such as COVID-19 is increasingly being recognized. However, little is presently known about the possible routes through which such personal preferences and cultural norms pertinent to social behaviors are formulated. Thus, in this paper, factors that can be potentially associated with individuals to self-regulate strict hand hygiene practices before the pandemic, during the state of emergency, and after the state of emergency was lifted in Japan are investigated. Focus is given to the handwashing education in primary school, a cultural practice originating from the old Shinto tradition, and individuals’ reciprocal inclinations. As people in Japan are known to be highly conscious of hygiene in all aspects of their daily life and are less likely to contract an infection, evidence obtained in this specific context could contribute to the better understanding of individuals’ health-related behaviors in general, and during crises in particular.

Methods
Using the data derived from a four-wave nationwide longitudinal online survey, we examined the extent to which elementary school education, childhood cultural experiences at shrines, and individual other-regarding preferences are associated with self-regulating hand hygiene practices prior to the pandemic and people’s efforts to comply with the government-imposed measures aimed at preventing the spread of COVID-19 infection during the state of emergency. We also investigated the long-term trends in the relationships among these factors (i.e., after the abolishment of the state of emergency) using panel data.

Results
Our findings reveal that childhood education and cultural experiences related to handwashing practices, as well as reciprocal inclinations, are significantly associated with Japanese attitudes toward personal hygiene (beyond handwashing practices) prior to, during, and after the state of emergency. In recognition of the possible effects of recall bias and measurement errors, several important attempts to mitigate these issues were made to strengthen the value of our findings.

Conclusions
The importance of school education received during childhood, as well as culture and other-regarding preferences, in the individual attitudes toward hand hygiene in adulthood highlighted in this study contributes to the better understanding of the role that these factors play in the variations in voluntary compliance with strict hand hygiene practices before and during an uncertain and prolonged crisis.
Dyspnea and outcome expectations are associated with physical activity in persons with pneumoconiosis: a cross-sectional study
Authors: Kawaji Tomohiro , Hasegawa Takashi , Uchiyama Yasushi 
Published: September 2022

Abstract
Background
There are various reports on factors associated with physical activity in patients with chronic respiratory diseases. However, there are no studies on the relationship between physical activity and psychological or environmental factors. In this study, we investigated the relationship between physical activity and psychological and environmental factors using questionnaires for patients with pneumoconiosis.

Methods
This cross-sectional study included patients with pneumoconiosis who underwent a pneumoconiosis health examination in 2019. A self-administered questionnaire was used to conduct the study. Physical activity was evaluated using the International Physical Activity Questionnaire, and subjective symptoms [dyspnea and quality of life (QOL)], environmental factors (environment around home and life space), psychological factors (depression, stage of change, self-efficacy, decisional balance, and outcome expectations), and others (e.g., experience with pulmonary rehabilitation) were investigated.

Results
The number of respondents in the study was 185 (men: 171, women: 14). Age, dyspnea, stage of change, self-efficacy, outcome expectations, QOL, depression, decisional balance, and life space were significantly correlated with physical activity. In the multivariate analysis, outcome expectations and dyspnea were extracted as independent factors. In the path analysis, outcome expectations and dyspnea had a direct influence on physical activity. Dyspnea directly impacted not only physical activity but also outcome expectations, stage of change, QOL, life space, and depression.

Conclusions
Dyspnea and outcome expectations were associated with physical activity in patients with pneumoconiosis. To improve physical activity in pneumoconiosis patients, it was suggested that it may be necessary to improve dyspnea and promote an understanding of physical activity.
Correlation of the prognostic value of FNDC4 in glioblastoma with macrophage polarization
Authors: Li Hongwu , Yan Xiaofei , Ou Shaowu 
Published: September 2022

Abstract
Background
Glioblastoma is among the most malignant tumors in the central nervous system and characterized by strong invasion and poor prognosis. Fibronectin type III domain-containing 4 (FNDC4) plays various important roles in the human body, including participating in cellular metabolism and inflammatory responses to cardiovascular diseases, influencing immune cells, and exerting anti-inflammatory effects; however, the role of FNDC4 in glioblastoma has not been reported.

Methods
In this study, bioinformatics databases, including TCGA, CGGA, GTEx, and TIMER, were used to analyze the differential expression of FNDC4 genes and cell survival, in addition to investigating its relationship with immune cell infiltration. Additionally, we overexpressed FNDC4 in glioblastoma cell lines U87 and U251 by lentiviral transfection and detected changes in proliferation, cell cycle progression, and apoptosis. Following collection of monocytes from the peripheral blood of healthy individuals and transformation into M0 macrophages, we performed flow cytometry to detect the polarizing effect of exogenous FNDC4, as well as the effect of FNDC4-overexpressing glioblastoma cells on macrophage polarization in a co-culture system.

Results
We identified that significantly higher FNDC4 expression in glioblastoma tissue relative to normal brain tissue was associated with worse prognosis. Moreover, we found that FNDC4 overexpression in U87 and U251 cells resulted in increased proliferation and affected the S phase of tumor cells, whereas cell apoptosis remained unchanged. Furthermore, exogenous FNDC4 inhibited the M1 polarization of M0 macrophages without affecting M2 polarization; this was also observed in glioblastoma cells overexpressing FNDC4.

Conclusions
FNDC4 expression is elevated in glioblastoma, closely associated with poor prognosis, and promoted the proliferation of glioblastoma cells, affected the S phase of tumor cells while inhibiting macrophage polarization.
Molecular mechanisms of inhibitor of growth (ING) family members in health and malignancy
Authors: Taheri Mohammad , Hussen Bashdar Mahmud , Najafi Sajad , Abak Atefe , Ghafouri-Fard Soudeh , Samsami Majid , Baniahmad Aria 
Published: September 2022

AbstractING genes belong to family of tumor suppressor genes with regulatory functions on cell proliferation, apoptosis, and cellular senescence. These include a family of proteins with 5 members (ING1-5), which are downregulated in human malignancies and/or affected by pathogenic mutations. ING proteins are highly evolutionarily conserved proteins containing several domains through which bind to chromatin structures by exerting their effects as readers of histone modification marks, and also binding to proteins like p53 involved in biological processes such as cell cycle regulation. Further, they are known as subunits of histone acetylation as well as deacetylation complexes and so exert their regulatory roles through epigenetic mechanisms. Playing role in restriction of proliferative but also invasive potentials of normal cells, INGs are particularly involved in cancer development and progression. However, additional studies and experimental confirmation are required for these models. This paper highlights the potential impact that INGs may have on the development of human cancer and explores what new information has recently arise on the functions of ING genes.
Prolonged postoperative length of stay may be a valuable marker for susceptibility to relapse beyond established risk factors in patients with stage III colon cancer
Authors: Emland Frans , Taflin Helena , Carlsson Göran , Ljungman David , Lindskog Elinor Bexe 
Published: September 2022

Abstract
Background
Delay from surgery to adjuvant chemotherapy causes impaired survival among patients undergoing radical resection for stage III colon cancer, and the underlying mechanism for this is incompletely clarified. It is established that prolonged postoperative hospital length of stay (LOS) is associated with delayed initiation of the adjuvant treatment driving the assumption that prolonged LOS is prognostically unfavorable due to this fact and case mix factors. We hypothesize that prolonged LOS after surgery is a valuable marker for susceptibility to relapse that is not detected in established prognostic factors and, alone, associated with a shorter disease-free survival (DFS).

Materials and methods
A total of 690 consecutive patients undergoing elective radical resection for stage III colon cancer in 2000–2015 were identified in a prospective detailed facility database. Univariate and multivariate analyses were performed using Cox proportional hazards model in the evaluation of LOS as an independent prognostic factor.

Results
Short postoperative LOS, low comorbidity, and few complications were associated with longer DFS (p < 0.01). Fewer patients in the short and intermediate LOS groups had a relapse in their disease (28% and 33%, respectively), compared to the patients with longer LOS (40%, p < 0.05). LOS was a prognostic factor for DFS in the unadjusted univariate model (HR 1.04 per unit change) and remained statistically significant in the adjusted multivariate analysis, with a HR of 1.03 per hospital day (p < 0.01).

Conclusions
Postoperative LOS independently correlates with the risk of recurrence and DFS, regardless of if adjuvant chemotherapy is given, along with the factors such as age, comorbidity, complications, and tumor features. We propose a further investigation into the causal mechanisms based on tumor and host biology linking LOS to DFS beyond established risk factors.
Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome
Authors: Hornby Brittany , Thompson William Reid , Almuqbil Mohammed , Manuel Ryan , Abbruscato Anthony , Carr Jim , Vernon Hilary J. 
Published: September 2022

Abstract
Background
Natural history studies are increasingly recognized as having an important role in drug development for rare diseases. A phase 3, observational, retrospective, and non-interventional study was designed to establish a natural history control (NHC) cohort of patients with Barth syndrome (BTHS) to provide further analysis of the efficacy of elamipretide observed in an open-label extension (OLE) phase of the TAZPOWER trial, a clinical trial that tested the efficacy of 40 mg daily of elamipretide in patients with BTHS.

Methods
This was a retrospective, non-interventional study. A propensity score model was used to compare elamipretide-treated patients and NHCs. The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).

Results
For the 6-min walk test (6MWT, primary endpoint), the least squares (LS) mean difference between groups was 79.7 m (P = 0.0004) at week 64 and 91.0 m (P = 0.0005) at week 76 in favor of elamipretide. Significant improvements in muscle strength (secondary endpoint), as assessed by handheld dynamometry (HHD) were also observed with elamipretide, with LS mean differences of 40.8 Newtons at 64 weeks (P = 0.0002) and 56.7 Newtons at 76 weeks (P = 0.0005). Patients continuously treated with elamipretide also experienced statistically significant improvements in other secondary endpoints (i.e., 5 times sit-to-stand [5XSST], multi-domain responder index [MDRI]). The functional improvements were robust to sensitivity analyses. Left ventricular stroke volume increased from baseline in patients with elamipretide but decreased in NHCs.

Conclusions
Overall, the study established a NHC for use in assessing the efficacy of therapeutic interventions in patients with BTHS and the results suggest that elamipretide may improve natural history of BTHS at least in part by attenuating the natural decline in heart function and provide meaningful improvements in heart function and functional capacity in patients with BTHS compared to NHCs.

Highlights

A matched Natural History Control (NHC) was used to evaluate elamipretide in BTHS

Elamipretide may improve natural history of BTHS by attenuating natural decline in heart function

Elamipretide was associated with meaningful clinical improvements in skeletal muscle and cardiovascular parameters that were not observed in NHCs

The study established a NHC for use in assessing the efficacy of therapeutic interventions in BTHS
Clinical phenotypes and genetic features of hereditary transthyretin amyloidosis patients in China
Authors: He Xinyue , Tian Zhuang , Guan Hongzhi , Zhang Shuyang 
Published: September 2022

Abstract
Background
Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature.

Methods
The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death.

Results
We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ2 = 26.885, P < 0.001).

Conclusions
This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years.
Health insurance literacy and health services access barriers in Niemann–Pick disease: the patient and caregiver voice
Authors: Diaz George A. , Crowe Joslyn , Hopkin Justin 
Published: September 2022

Abstract
Background
Major challenges to health care access include low health insurance literacy, prohibitive costs, and insurance barriers. Niemann–Pick disease (NPD), comprising acid sphingomyelinase deficiency (ASMD) and Niemann–Pick type C (NPC), is a group of rare, autosomal recessive, highly heterogeneous, neurovisceral, life-threatening, relentlessly progressive lysosomal disorders. Patients experience debilitating systemic and neurological symptoms and substantial emotional and financial stress. Currently, these multifaceted disorders are managed symptomatically as there are no approved therapies. Given the considerable disease burden of NPD, timely access to quality health care is paramount for improving outcomes in these life-threatening disorders. Understanding health insurance literacy and access challenges among patients with NPD and their caregivers is a first step to overcoming treatment barriers.

Results
Patients from the Niemann–Pick community participated in a health insurance literacy survey and follow-up telephone interviews on perceived access challenges. Of the 79 respondents who completed the survey, 67 participated in interviews. All respondents had stable health insurance coverage. However, 61% of respondents were unaware of Medicaid waivers and did not avail of them. Overall, 50% of respondents with childhood onset NPC selected Medicaid/Medicare and private insurance; 35% utilized Medicaid waivers. Most respondents with ASMD had private insurance only. Although the Niemann–Pick community demonstrated greater health insurance literacy than the general population, knowledge gaps exist in calculating insurance coverage, out-of-pocket maximums, and defining a formulary. The most frequently cited access burden was the process of obtaining medical care and services. Among respondents with ASMD, the greatest access burden was fear of unavailability of or access to medications and treatment. Access challenges adversely impacted patients’ mental health and exacerbated physical symptoms. Delays and denials in obtaining essential medication, equipment, and services contributed to disease progression. Caregivers faced burnout and often questioned the utility of their advocacy.

Conclusions
This study identified knowledge gaps in health insurance literacy and challenges to access medication and health care services among individuals impacted by NPD. Patients and caregivers need the knowledge and skills to navigate a complicated health care system, understand their rights to medication and services and, ultimately, benefit from improved outcomes, especially in a post–drug approval era.
An international study of caregiver-reported burden and quality of life in metachromatic leukodystrophy
Authors: Sevin Caroline , Barth Magalie , Wilds Alexandra , Afriyie Abena , Walz Markus , Dillon Annamarie , Howie Kenneth , Pang Francis 
Published: September 2022

Abstract
Background
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by mutations in the arylsulfatase A gene. Until now, there has been little information on the burden of MLD on patients and their caregivers. This multinational study aims to quantify caregiver-related impacts of MLD across several key domains including symptoms, treatment burden, time investment, social and emotional well-being, and professional and financial impact.

Results
Data were collected through moderator-assisted web survey and telephone interviews. The survey was developed with extensive input from clinical experts and MLD patient advocacy groups. The EQ-5D-5L questionnaire was administered during follow-up interviews. The total sample consisted of parents of MLD patients in the US (n = 10), France (n = 10), Germany (n = 6), UK (n = 5), Belgium (n = 1), and Norway (n = 2). The impact of MLD is evident from the EQ-5D-5L scores, which indicate utility values for caregivers below respective national population norms and a higher proportion of caregivers reporting problems with anxiety/depression. Time involved for care was demonstrated by a mean of 4.1 inpatient and 29.6 outpatient hospital visits in the previous 12-month period. These commitments place stress on familial relationships with 50% of caregivers reporting their child’s MLD diagnosis had negatively impacted their relationship with their spouse/partner. Professionally, 76.5% of caregivers stopped working or switched to part-time employment following their child’s MLD diagnosis, and most acknowledged caring for their child had affected their potential for career progression or promotion. Differences are also observed based on late infantile versus juvenile onset MLD, time since diagnosis, and for transplanted patients versus those who received palliative care only.

Conclusions
This multinational study demonstrates that MLD consistently negatively affects many aspects of caregivers’ lives including health, relationships, and professional status, irrespective of location. We expect that the results of this study are generalizable to other countries. This study enhances our understanding of MLD caregiver impacts, which could improve patient care and assist in identifying support for individuals with MLD and their families.
Clinical efficacy of mandibular complete dentures with a resilient liner: study protocol for a multicenter randomized controlled trial
Authors: Kimoto Katsuhiko , Kimoto Suguru , Hoshi Noriyuki , Sato Yusuke , Yoneyama Yoshikazu , Takebe Jun , Ichikawa Tetsuo , Murata Hiroshi , Nishimura Masahiro , Minakuchi Shunsuke , Kawai Yasuhiko 
Published: September 2022

Abstract
Background
During restoration of poorly fitting complete dentures (CDs) in edentulous patients, liners are used to reconstruct the concave surfaces of CDs with a new base material. These relining materials are classified into resilient liners (RLs) and non-resilient liners (NRLs), but the clinical effects of these liners and their selection criteria remain unclear. The purpose of this study is to evaluate the clinical efficacy of relining mandibular CDs using RL and NRL and to conduct a follow-up study.

Methods
The study is currently being conducted at eight centers, and a parallel-group randomized controlled trial (RCT) is underway. One hundred thirty-two edentulous patients with poorly fitting mandibular CDs will be assigned to two groups based on whether they will receive RL or NRL. Participants will have an RL or NRL applied for relining their CDs using an indirect method of dynamic impressions. Data will be recorded at 1 week and 3, 6, and 12 months after denture delivery. The primary outcome will be assessment of the patients’ general satisfaction by using a 100-mm visual analog scale (VAS). Secondary outcomes will be measured as patient-reported outcomes, including food intake status and oral hygiene-related quality of life. Masticatory performance and the number of sore spots on the oral mucosa will also be recorded. Comparisons between the two groups and within-subject comparisons of pre- and post-intervention measurements will be conducted.

Discussion
For dentists and prosthetic researchers in Japan, this RCT will provide information on the clinical efficacy of RL materials in comparison to RNL in CD wearers. The new evidence regarding the use of RL materials in an aging population will also be useful to dentists in other countries in their routine clinical practice.

Trial registration
This clinical trial has been registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000041950).