bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort
Authors: Pasutharnchat Nath , Taychargumpoo Chamaiporn , Vorasettakarnkij Yongkasem , Amornvit Jakkrit 
Published: May 2021

Abstract
Background
Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients.

Methods
The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed.

Results
Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10–92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3–9).

Conclusions
This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.
Identifying outcomes reported in exercise interventions in oesophagogastric cancer survivors: a systematic review
Authors: O’Connor Louise , Smyth Emily , Bennett Annemarie E. , Smith Valerie , O’Neill Linda , Reynolds John V. , Hussey Juliette , Guinan Emer 
Published: May 2021

Abstract
Background
Research investigating exercise interventions in oesophagogastric cancer survivors is sparse, and the outcomes are varied. The aim of this systematic review is to identify the domains and outcomes reported in exercise interventions in oesophagogastric cancer survivors to be included in a Delphi study, with a view to informing the development of a core outcome set (COS).

Methods
EMBASE, PubMed, CINHAL, Cochrane Library, SCOPUS, and PEDro were searched up to March 2020 using a predefined search strategy. The outcomes identified during data extraction were categorised using the core areas outlined in the OMERACT Filter 2.0.

Results
Fourteen domains and 63 outcomes were identified. The most frequently reported outcomes were in the domains of quality of life using the EORTC-QLQ-C30 questionnaire and the relevant disease-specific modules (100%), exercise capacity/fitness/physical function (100%), anthropometrics (83.33%), physical activity (66.67%), and biomarker analysis (50%).

Conclusion
This systematic review quantifies and describes the domains and outcomes examined in exercise interventions in oesophagogastric cancer survivors. Some inconsistency exists within the domains and outcomes used, and little attention was given to nutritional or economic endpoints. In order to develop a COS, a Delphi consensus process with key stakeholders is needed to identify the relevant domains and outcomes for inclusion.
Characterization of alternative splicing events and prognostic signatures in breast cancer
Authors: Han Pihua , Zhu Jingjun , Feng Guang , Wang Zizhang , Ding Yanni 
Published: May 2021

Abstract
Background
Breast cancer (BRCA) is one of the most common cancers worldwide. Abnormal alternative splicing (AS) frequently observed in cancers. This study aims to demonstrate AS events and signatures that might serve as prognostic indicators for BRCA.

Methods
Original data for all seven types of splice events were obtained from TCGA SpliceSeq database. RNA-seq and clinical data of BRCA cohorts were downloaded from TCGA database. Survival-associated AS events in BRCA were analyzed by univariate COX proportional hazards regression model. Prognostic signatures were constructed for prognosis prediction in patients with BRCA based on survival-associated AS events. Pearson correlation analysis was performed to measure the correlation between the expression of splicing factors (SFs) and the percent spliced in (PSI) values of AS events. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to demonstrate pathways in which survival-associated AS event is enriched.

Results
A total of 45,421 AS events in 21,232 genes were identified. Among them, 1121 AS events in 931 genes significantly correlated with survival for BRCA. The established AS prognostic signatures of seven types could accurately predict BRCA prognosis. The comprehensive AS signature could serve as independent prognostic factor for BRCA. A SF-AS regulatory network was therefore established based on the correlation between the expression levels of SFs and PSI values of AS events.

Conclusions
This study revealed survival-associated AS events and signatures that may help predict the survival outcomes of patients with BRCA. Additionally, the constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.
ALDH2 polymorphism rs671 is a predictor of PD-1/PD-L1 inhibitor efficacy against thoracic malignancies
Authors: Matsumoto Akiko , Nakashima Chiho , Kimura Shinya , Sueoka Eizaburo , Aragane Naoko 
Published: May 2021

Abstract
Background
Aldehyde dehydrogenase 2 (ALDH2) plays an important role in the endogenous aldehyde detoxification of various types of cells. ALDH2*2, a variant allele of the ALDH2 polymorphism rs671, leads to decreased enzymatic activity. ALDH2*2 may enhance tumor antigen presentation due to aldehyde-induced DNA damage while suppressing peripheral blood T cell counts and T cell activation.

Methods
On the basis of our hypothesis that rs671 affects the sensitivity of immune checkpoint inhibitors (ICIs), we evaluated the effects of rs671 on patients with thoracic malignancies who started ICI therapy in 2016–2019. The cohort consisted of 105 cases, including 64 cases with adenocarcinoma and 30 cases with squamous cell carcinoma, 49 of whom were ALDH2*2 carriers. The first ICI was PD-1/PD-L1 inhibitor (Nivolumab, Pembrolizumab, or Atezolizumab) in all cases.

Results
The best response to anti-PD-1/PD-L1 therapy (partial response/stable disease/progressive disease) was 36%/50%/14% in the rs671(−) cases; however, the response was relatively poor in the rs671(+) cases (27%/29%/45%, respectively) (p = 0.002). The hazard ratio (95% confidence interval) of disease progression within the observation period of 6 months for the rs671(+) cases was estimated to be 5.0 (2.5–10) after the adjustment for covariates, including sex, Brinkman index, treatment line, tumor tissue programmed death-ligand 1 positivity rate, tumor tissue EGFR mutation. This association was also maintained in a stratified analysis, suggesting that ALDH2*2 is an independent negative predictive factor for the short-term prognosis of anti-PD-1/PD-L1 therapy. Thus, the progression-free survival (PFS) ratio of the rs671(+) cases decreased rapidly after ICI initiation but was eventually higher than that of the rs671(−) cases (restricted mean survival time in 12 months from 2 to 3 years afterward was 1.3 times that of the rs671(−) cases). Moreover, the highest PFS ratio after 2 years among sub-groups was found in the first-line treatment sub-group of rs671(+) group (40%).

Conclusions
Our study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.
Effectiveness of self-help workbook intervention on quality of life in cancer patients receiving chemotherapy: results of a randomized controlled trial
Authors: Takano Toshimi , Matsuda Ayako , Ishizuka Noriko , Ozaki Yukinori , Suyama Koichi , Tanabe Yuko , Miura Yuji , Matsushima Eisuke 
Published: May 2021

Abstract
Background
A self-help workbook is expected to support cancer patients to cope with physical and psychosocial distress, to facilitate communication with medical staff, and to improve quality of life (QOL). We conducted a randomized controlled trial to evaluate the effectiveness of a self-help workbook intervention on QOL and survival.

Methods
From June 2014 to March 2015, patients with breast, colorectal, gastric, and lung cancer receiving outpatient chemotherapy were randomized into an intervention group (n = 100) or control group (n = 100). Intervention group participants received workbooks originally made for this study, read advice on how to cope with distress, and filled out questionnaires on the workbooks periodically. EORTC QLQ-C30 was evaluated at baseline, at 12 weeks, and at 24 weeks. The primary endpoint was Global Health Status / QOL scale (GQOL).

Results
No significant interaction was observed between the intervention and time in terms of GQOL or any of the functional scales. Among the 69 patients who continued cytotoxic chemotherapy at 24 weeks, the intervention was significantly associated with improved emotional functioning scores (P = 0.0007). Overall survival was not significantly different between the two groups.

Conclusions
Self-help workbook intervention was feasible in cancer patients receiving chemotherapy. Although the effect of the intervention was limited, a post-hoc subset analysis suggested that the intervention may improve emotional functioning among patients who receive long-term cytotoxic chemotherapy.

Trial registration
UMIN Clinical Trials Registry, UMIN000012842. Registered 14 January 2014.
Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors
Authors: Anwar Sumadi Lukman , Cahyono Roby , Prabowo Dayat , Avanti Widya Surya , Choridah Lina , Dwianingsih Ery Kus , Harahap Wirsma Arif , Aryandono Teguh 
Published: May 2021

Abstract
Background
Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes.

Methods
Non-metastatic breast cancer patients (N = 1081) treated in our department (2014–2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years.

Results
Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071–1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090–2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139–2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035–3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors.

Conclusion
Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients’ quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.
Rickets manifestations in a child with metaphyseal anadysplasia, report of a spontaneously resolving case
Authors: Diaz Escagedo Patricia , Fiscaletti Melissa , Olivier Patricia , Hudon Chloé , Miranda Valancy , Miron Marie-Claude , Campeau Philippe M. , Alos Nathalie 
Published: May 2021

Abstract
Introduction
Rickets is not an unusual diagnosis for pediatricians even currently in developed countries. Children typically present with leg bowing, enlargement of wrists, rachitic rosary (swelling of costochondral junctions) and/or waddling gait. But not every child with growth delay and enlarged metaphyses is diagnosed with rickets. Metaphyseal anadysplasia (MAD) is a disorder of variable severity with metaphyseal flaring and irregularities, without vertebral abnormalities. MAD is characterized by an early onset and a regressive course in late childhood without treatment, despite persistent short stature. Autosomal dominant or recessive variants in the matrix metalloproteinase 13 gene (MMP13) are responsible for these transient metaphyseal changes.

Case presentation
We report a new pathogenic heterozygous variant in MMP13 (NM_002427.4: c.216G>C, p.Gln72His) in a toddler, initially thought to have rickets, and his father, with MAD phenotypes. Additionally, we review the seven reported MMP13 variants.

Conclusion
One should keep a wide differential diagnosis in cases of suspected rickets, including skeletal dysplasias which might have a regressive course.
An investigation of the association between religious coping, fatigue, anxiety and depressive symptoms during the COVID-19 pandemic in Morocco: a web-based cross-sectional survey
Authors: Zarrouq Btissame , Abbas Nivine , Hilaly Jaouad El , Asri Achraf El , Abbouyi Samira , Omari Majid , Malki Hicham , Bouazza Samira , Moutawakkil Salma Ghofrane , Halim Karima , Ragala Mohammed Elamine 
Published: May 2021

AbstractBackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic has triggered fear and distress among the public, thus potentiating the incidence rate of anxiety and depression. This study aims to investigate the psychological effect of quarantine on persons living in Morocco when the first COVID-19 cases were identified. The associations between anxiety, depression symptoms, and their predictors (sociodemographics, fatigue, and religious coping) were examined.MethodsA web-based cross-sectional survey, with a total of 1435 participants (≥18 years) recruited anonymously, was conducted during the COVID-19 pandemic (from 3 to 30 April 2020). A structured questionnaire was used to assess psychosocial factors, COVID-19 epidemic-related factors, and religious coping. Religious coping, fatigue, and depression, and anxiety were measured by Brief Religious Coping Scale (Brief RCOPE), Chalder Fatigue Scale (CFS), and Hospital Anxiety and Depression Scale (HADS), respectively. A generalized linear model (logistic regression) was used to determine the predictive factors of depression and anxiety.ResultsThe prevalence of anxiety and depression was 43.0% (n = 621) and 53.0% (n = 766), respectively. Both were associated with female gender, household income decline, tracking COVID-19 news, and fear to contract COVID-19 (aOR = 1.36 to 2.85). Additionally, 32.0% (n = 453) and 26.0% (n = 372) reported severe physical fatigue, and mental fatigue, respectively. Both latter factors were significantly and positively associated with depression as well as with anxiety. Depressive and anxious patients used more negative religious coping, while positive religious coping was slightly associated with depression.ConclusionIn this online survey of the general population in Morocco, anxiety and depressive symptoms are prevalent during the COVID-19 pandemic. Pandemic and psychosocial factors, such as female gender, income decline, infection fears, massive COVID-19 news exposure, negative religious coping, and fatigue were associated with increased risk of depression and anxiety symptoms. Psychosocial and financial support should be provided to the quarantined population.
Facilitators and barriers to healthy eating in a worksite cafeteria: a qualitative study
Authors: Stern Dalia , Blanco Ilian , Olmos Lucy A. , Valdivia Joel J. , Shrestha Archana , Mattei Josiemer , Spiegelman Donna 
Published: May 2021

Abstract
Background
Worksite-based nutrition interventions can serve as access points to facilitate healthy eating and translate existing knowledge of cardiometabolic disease prevention. We explored perceptions, facilitators, and barriers for healthy eating in a cafeteria at a large worksite in Mexico City.

Methods
We conducted an exploratory qualitative study in a large department store in Mexico City with ~ 1500 employees. We conducted eight focus group discussions (FGD) with 63 employees stratified by job category (sales, maintenance, shipping, restaurant, cafeteria, administrative staff, and sales managers). Employees were invited to participate in the FGD if they were at the store at the day and time of the FGD for their job type. FGDs were audio-recorded, transcribed verbatim and analyzed using the thematic method. This process involved the researches´ familiarizing themselves with the data, generating initial codes, searching for themes, reviewing the themes, defining and naming themes, and then interpreting the data.

Results
Employees defined healthy eating as eating foods that are fresh, diverse, and prepared hygienically. The most commonly reported facilitators of healthy eating at the worksite were availability of affordable healthy food options and employees’ high health awareness. Major barriers to healthy eating included unavailability of healthy foods, unpleasant taste of food, and preference for fatty foods and meat. For lower-wage workers, affordability was a major concern. Other barriers included lack of time to eat work and long working hours.

Conclusion
A broad range of factors affect healthy eating at the cafeteria, some related to nutrition and some related to the employees type of job. Availability of healthy, hygienic, and tasty food at an affordable price could lead to healthier food choices in the worksite cafeteria. These strategies, along with work schedules that allow sufficient time for healthy eating, may help improve dietary behaviors and health of employees.
Exploring the spatial-temporal distribution and evolution of population aging and social-economic indicators in China
Authors: Man Wang , Wang Shaobin , Yang Hao 
Published: May 2021

Abstract
Background
China is one of the world’s fastest-aging countries. Population aging and social-economic development show close relations. This study aims to illustrate the spatial-temporal distribution and movement of gravity centers of population aging and social-economic factors and thier spatial interaction across the provinces in China.

Methods
Factors of elderly population rate (EPR), elderly dependency ratio (EDR), per capita gross regional product (GRPpc), and urban population rate (UPR) were collected. Distribution patterns were detected by using global spatial autocorrelation, Kernel density estimation, and coefficient of variation. Further, Arc GIS software was used to find the gravity centers and their movement trends yearly from 2002 to 2018. The spatial interaction between the variables was investigated based on bivariate spatial autocorrelation analysis.

Results
The results showed a larger variety of global spatial autocorrelation indexed by Moran’s I and stable trends of dispersion degree without obvious convergence in EPR and EDR. Furthermore, the gravity centers of the proportion of EPR and EDR moved northeastward. In contrast, the economic and urbanization factors showed a southwestward movement, which exhibited an reverse trend compared to population aging indicators. Moreover, the movement rates of EPR and EDR (15.12 and 18.75 km/year, respectively) were higher than that of GRPpc (13.79 km/year) and UPR (6.89 km/year) annually during the study period. Further, the bivariate spatial autocorrelation variation is in line with the movement trends of gravity centers which showed a polarization trend of population aging and social-economic factors that the difference between southwest and northeast directions and exhibited a tendency to expand in China.

Conclusions
In sum, our findings revealed the difference in spatio-temporal distribution and variation between population aging and social-economic factors in China. It further indicates that the opposite movements of gravity centers and the change of the BiLISA in space which may result in the increase of the economic burden of the elderly care in northern China. Hence, future development policy should focus on the social-economic growth and distribution of old-aged supporting resources, especially in northern China.
Downregulation of the PD-1/PD-Ls pathway in peripheral cells correlates with asbestosis severity
Authors: Qiu Meihua , Chen Yuqing , Ye Qiao 
Published: May 2021

Abstract
Background
Asbestosis and silicosis are characterized by diffuse or nodular interstitial lung fibrosis resulting from exposure to asbestos or silica dust, respectively. This study was designed to detect programmed cell death protein (PD-1)/programmed death ligands (PD-Ls) expression in patients with asbestosis and silicosis and to explore the possible clinical significance of PD-1/PD-Ls expression in patients with the two diseases.

Methods
Thirty patients with asbestosis, 23 patients with silicosis and 25 healthy controls were consecutively recruited and provided informed consent to participate in the study. Clinical data were collected from patients’ clinical charts. PD-1/PD-Ls expression in peripheral blood (PB) was detected using flow cytometry.

Results
PD-1 was expressed at significantly lower levels on CD4+ or CD8+ peripheral T cells from patients with asbestosis and silicosis than on cells from healthy controls. Similarly, significantly lower PD-L1 and PD-L2 expression was detected on CD14+ monocytes from patients with asbestosis and silicosis than on cells from healthy controls. In addition, no significant differences in PD-1, PD-L1 and PD-L2 expression were observed between the asbestosis and silicosis groups. Moreover, the proportions of PD-1+ CD4+ T cells and PD-1+ CD8+ T cells in patients with asbestosis were positively correlated with the percentage of forced vital capacity predicted.

Conclusions
Decreased PD-1 expression on CD4+ T or CD8+ T cells in PB was positively correlated with the asbestosis severity, implying that pulmonary fibrosis development in patients with asbestosis was positively correlated with the downregulation of the PD-1/PD-Ls pathway.