bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus
Authors: Fatehi Farzad , Ashrafi Mahmoud Reza , Babaee Marzieh , Ansari Behnaz , Beiraghi Toosi Mehran , Boostani Reza , Eshraghi Peyman , Fakharian Atefeh , Hadipour Zahra , Haghi Ashtiani Bahram , Moravej Hossein , Nilipour Yalda , Sarraf Payam , Sayadpour Zanjani Keyhan , Nafissi Shahriar 
Published: September 2021

Background: Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing.Objective: This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities.Methods: A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members.Conclusion: Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease.
Prognostic and Predicted Significance of FENDRR in Colon and Rectum Adenocarcinoma
Authors: Yang Fan , Sun Siyu , Yang Fei 
Published: September 2021

BackgroundThe role of fetal-lethal non-coding developmental regulatory RNA (FENDRR) has been explored in various cancers; however, its relationship with colon adenocarcinoma/rectum adenocarcinoma (COAD/READ) remains unclear. The objectives of this study were to identify and assess any associations between FENDRR and COAD/READ using The Cancer Genome Atlas (TCGA) database and the Genetic Data Commons (GDC) Data Portal.MethodsThe records of patients with COAD/READ were collected from the GDC Data Portal. After comparing the expression level of FENDRR in COAD/READ and healthy tissues, we evaluated the association of FENDRR with clinicopathological characters and the survival rate, the impact of FENDRR on prognosis, the biological function of FENDRR, and the relative abundance of tumor-infiltrating immune cells in patients with COAD/READ. Moreover, we aimed to construct a protein-protein interaction (PPI) network for selecting genes and a ceRNA network for presenting mRNA-miRNA-lncRNA interactions.ResultsIn patients with COAD/READ, FENDRR expression could differentiate tumor tissues from the adjacent healthy tissues since it was significantly lower in the former than in the latter. High FENDRR expression was correlated with poorer survival and higher tumor stage, current tumor stage, and metastasis stage, and also exhibited high scores for apoptosis, autophagy, and senescence. Immune cell infiltration analysis showed that the high expression group had significantly lower immune and stromal scores. Low FENDRR expression was correlated with poor overall survival (OS), and thus, it could serve as an independent risk factor. The prognostic models constructed in the study performed well for the prediction of OS and disease-specific survival (DFS) using FENDRR expression. Gene set enrichment analysis revealed that vascular smooth muscle contraction, melanogenesis, basal cell carcinoma, and Hedgehog signaling pathways were significantly enriched in patients with high FENDRR expression. Eight hub genes, namely, PKM, ALDOA, PFKP, ALDOC, PYGL, CTNNB1, PSMA5, and WNT5A, were selected from the PPI network, and a ceRNA network was constructed based on the differentially expressed mRNAs, miRNAs, and lncRNAs to illustrate their regulatory relationships.ConclusionFENDRR may serve as a potential biomarker for the diagnosis and prognosis of COAD/READ.
Cathepsins B, D, and G Are Expressed in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma
Authors: Humphries Felix , Chang-McDonald Bridget , Patel Josie , Bockett Nicholas , Paterson Erin , Davis Paul F. , Tan Swee T. 
Published: September 2021

AimWe have previously demonstrated the presence of two cancer stem cell (CSC) subpopulations within metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC) expressing components of the renin-angiotensin system (RAS), which promotes tumorigenesis. Cathepsins B, D and G are enzymes that constitute bypass loops for the RAS. This study investigated the expression and localization of cathepsins B, D, and G in relation to CSC subpopulations within mHNcSCC.MethodsImmunohistochemical staining was performed on mHNcSCC tissue samples from 20 patients to determine the expression and localization of cathepsins B, D, and G. Immunofluorescence staining was performed on two of these mHNcSCC tissue samples by co-staining of cathepsins B and D with OCT4 and SOX2, and cathepsin G with mast cell markers tryptase and chymase. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed on five mHNcSCC samples and four mHNcSCC-derived primary cell lines, to determine protein and transcript expression of these three cathepsins, respectively. Enzyme activity assays were performed on mHNcSCC tissue samples to determine whether these cathepsins were active.ResultsImmunohistochemical staining demonstrated the presence of cathepsins B, D and G in in all 20 mHNcSCC tissue samples. Immunofluorescence staining showed that cathepsins B and D were localized to the CSCs both within the tumor nests and peri-tumoral stroma (PTS) and cathepsin G was localized to the phenotypic mast cells within the PTS. Western blotting demonstrated protein expression of cathepsin B and D, and RT-qPCR demonstrated transcript expression of all three cathepsins. Enzyme activity assays showed that cathepsin B and D to be active.ConclusionThe presence of cathepsins B and D on the CSCs and cathepsin G on the phenotypic mast cells suggest the presence of bypass loops for the RAS which may be a potential novel therapeutic target for mHNcSCC.
Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma
Authors: Placke Jan-Malte , Soun Camille , Bottek Jenny , Herbst Rudolf , Terheyden Patrick , Utikal Jochen , Pföhler Claudia , Ulrich Jens , Kreuter Alexander , Pfeiffer Christiane , Mohr Peter , Gutzmer Ralf , Meier Friedegund , Dippel Edgar , Weichenthal Michael , Zimmer Lisa , Livingstone Elisabeth , Becker Jürgen C. , Lodde Georg , Sucker Antje , Griewank Klaus , Horn Susanne , Hadaschik Eva , Roesch Alexander , Schadendorf Dirk , Engel Daniel Robert , Ugurel Selma 
Published: September 2021

BackgroundPD-1-based immune checkpoint blockade (ICB) is a highly effective therapy in metastatic melanoma. However, 40-60% of patients are primarily resistant, with valid predictive biomarkers currently missing. This study investigated the digitally quantified tumor PD-L1 expression for ICB therapy outcome prediction.Patients and MethodsTumor tissues taken prior to PD-1-based ICB for unresectable metastatic disease were collected within the prospective multicenter Tissue Registry in Melanoma (TRIM). PD-L1 expression (clone 28-8; cut-off=5%) was determined by digital and physician quantification, and correlated with therapy outcome (best overall response, BOR; progression-free survival, PFS; overall survival, OS).ResultsTissue samples from 156 patients were analyzed (anti-PD-1, n=115; anti-CTLA-4+anti-PD-1, n=41). Patients with PD-L1-positive tumors showed an improved response compared to patients with PD-L1-negative tumors, by digital (BOR 50.5% versus 32.2%; p=0.026) and physician (BOR 54.2% versus 36.6%; p=0.032) quantification. Tumor PD-L1 positivity was associated with a prolonged PFS and OS by either digital (PFS, 9.9 versus 4.6 months, p=0.021; OS, not reached versus 13.0 months, p=0.001) or physician (PFS, 10.6 versus 5.6 months, p=0.051; OS, not reached versus 15.6 months, p=0.011) quantification. Multivariable Cox regression revealed digital (PFS, HR=0.57, p=0.007; OS, HR=0.44, p=0.001) and physician (OS, HR=0.54, p=0.016) PD-L1 quantification as independent predictors of survival upon PD-1-based ICB. The combination of both methods identified a patient subgroup with particularly favorable therapy outcome (PFS, HR=0.53, p=0.011; OS, HR=0.47, p=0.008).ConclusionPre-treatment tumor PD-L1 positivity predicted a favorable outcome of PD-1-based ICB in melanoma. Herein, digital quantification was not inferior to physician quantification, and should be further validated for clinical use.
Complex Regional Pain Syndrome. A Comprehensive Review on Neuroplastic Changes Supporting the Use of Non-invasive Neurostimulation in Clinical Settings
Authors: Zangrandi Andrea , Allen Demers Fannie , Schneider Cyril 
Published: September 2021

Background: Complex regional pain syndrome (CRPS) is a rare debilitating disorder characterized by severe pain affecting one or more limbs. CRPS presents a complex multifactorial physiopathology. The peripheral and sensorimotor abnormalities reflect maladaptive changes of the central nervous system. These changes of volume, connectivity, activation, metabolism, etc., could be the keys to understand chronicization, refractoriness to conventional treatment, and developing more efficient treatments.Objective: This review discusses the use of non-pharmacological, non-invasive neurostimulation techniques in CRPS, with regard to the CRPS physiopathology, brain changes underlying chronicization, conventional approaches to treat CRPS, current evidence, and mechanisms of action of peripheral and brain stimulation.Conclusion: Future work is warranted to foster the evidence of the efficacy of non-invasive neurostimulation in CRPS. It seems that the approach has to be individualized owing to the integrity of the brain and corticospinal function. Non-invasive neurostimulation of the brain or of nerve/muscles/spinal roots, alone or in combination with conventional therapy, represents a fertile ground to develop more efficient approaches for pain management in CRPS.
Study on the Hepatoprotection of Schisandra chinensis Caulis Polysaccharides in Nonalcoholic Fatty Liver Disease in Rats Based on Metabolomics
Authors: Feng Yanbo , Li Han , Chen Cong , Lin Hao , Xu Guangyu , Li He , Wang Chunmei , Chen Jianguang , Sun Jinghui 
Published: September 2021

The aim of this study was to investigate the hepatoprotection of Schisandra chinensis Caulis polysaccharides (SCPs) in the nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) in rats. A total of 30 Wistar rats were randomly divided into the control group (CON), model group (MOD), and Schisandra chinensis caulis polysaccharide (SCP) group. Except for those in the CON group, the other rats were fed with high-fat diet for 4 weeks to establish an NAFLD model. From the 5th week, rats in the SCP group were given SCP solution (100 mg kg−1) by gavage for 6 weeks, and those in the CON and MOD groups were given an equal volume of distilled water in the same way. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels in serum, the malondialdehyde (MDA) level, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in the liver tissue were detected. The small molecular metabolites in the blood of rats were determined by the metabolomics method of ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) combined with multivariate analysis. The enrichment analysis and pathway analysis of the different metabolites were carried out. The therapeutic mechanism of SCP in NAFLD rats was verified by western blot. The results showed that the levels of AST, ALT, TG, TC, and LDL-C in the serum of rats in the SCP group were significantly lower, and the levels of HDL-C were significantly higher than those in the MOD group. The screening and analysis of the metabolic pathways showed that SCP could alleviate the development of NAFLD by regulating the expression of UDP-glucose pyrophosphorylase (UGP2), UDP-glucose 6-dehydrogenase (UGDH), acetyl CoA carboxylase (ACC), and fatty acid synthase (FAS) in the liver of NAFLD rats. This study may provide a theoretical basis for the development and utilization of SCP.
Comparative Efficacy of Jaungo, A Traditional Herbal Ointment, and the Water-in-Oil Type Non-Steroidal Moisturizer for Radiation-Induced Dermatitis in Patients With Breast Cancer: A Study Protocol for a Prospective, Randomized, Single-Blinded, Pilot Study
Authors: Kim Eun Hye , Yoon Jee-Hyun , Park Su Bin , Lee Jee Young , Chung Weon Kuu , Yoon Seong Woo 
Published: September 2021

Background: Radiation-induced dermatitis (RID) is a common complication of radiation therapy (RT). Although it has a high prevalence and can even trigger the premature end of conventional cancer therapies, there is no standard management. This study aims to evaluate whether topical use of Jaungo (Shiunko), a traditional herbal ointment mainly composed of Lithospermi radix and Angelica sinensis, could reduce RID compared to the water-in-oil type non-steroidal moisturizer in patients with breast cancer.Methods: This is a prospective, single-blinded, randomized controlled pilot trial that investigates the effect of topical application of Jaungo for the prevention of RID in postoperative breast cancer patients scheduled for RT, in comparison with the non-steroidal moisturizer, with a random distribution of 50 patients across the two groups. RT will be administered for 5–7 weeks with a biological equivalent dose (BED10) of 60 Gy or more, and the interventions will be applied 3 times a day during RT duration. Participants will be assessed a total of nine times, including eight visits during the period of RT and one visit at a 2-week follow-up period after the end of treatment. The incidence and severity of RID, quality of life, skin reaction symptoms, and maximum pain related to RID will be measured. The incidence rate of grade 2 or higher RID using the Radiation Therapy Oncology Group (RTOG) in the two groups will be statistically compared as the primary outcome. The types and frequencies of adverse events will be also collected and evaluated. All assessments will be performed by independent radiology oncologists.Discussion: This trial is currently ongoing and is recruiting. This study will determine the preventive efficacy of Jaungo in RID with postoperative breast cancer patients and provide evidence in traditional Korean medicine clinical practice.
The Impact of COVID-19 on Sleep in Autistic Adults: Longitudinal Comparisons pre and During Lockdown
Authors: Halstead Elizabeth J. , Sullivan Emma C. , Dimitriou Dagmara 
Published: September 2021

Background: The longer-term impact of the pandemic on autistic adults' sleep are yet to be revealed, with studies concentrating on sleep in autistic children or mental health outcomes and coping strategies of autistic adults. Given the prevalence of sleep problems experienced by autistic adults and the changes in routine that have occurred as a result of COVID-19 societal restrictions, this study assessed the impact of the COVID-19 pandemic on sleep problems via a longitudinal subjective assessment method.Methods: Sleep data were gathered at three time points from 95 autistic adults, namely prior to the pandemic, at the start of COVID-19 and several months into COVID-19 to obtain a rich longitudinal dataset ascertaining how/if sleep patterns have changed in autistic adults over these several months.Results: In comparison to pre-lockdown, several sleep components were shown to improve during the lockdown. These improvements included reduced sleep latency (time taken to fall asleep), longer sleep duration, improved sleep efficiency, improved sleep quality, as well as improved daytime functioning. Pre-sleep cognitive arousal scores were found to decrease compared to pre-lockdown, meaning cognitive arousal improved. Approximately 65% of participants reported that they felt their sleep had been impacted since COVID-19 since Time 1, with the most common reasons reported as waking up exhausted (36.92%), not being able to get to sleep (33.85%), waking up in the night (29.23%), having a disrupted sleep pattern (27.69%), and nightmares (18.46%).Conclusions: Improvements in sleep may be related to societal changes (e.g., working from home) during the pandemic. Some of these changes are arguably beneficial for autistic adults in creating a more autism-inclusive society, for example telehealth opportunities for care. Further exploration of the associations between mental health and sleep are warranted.
Effects of Coronavirus-19 Induced Loneliness on Mental Health: Sleep Quality and Intolerance for Uncertainty as Mediators
Authors: Gu Simeng , He Zhengming , Sun Lianwang , Jiang Yao , Xu Minghong , Feng Guangkui , Ma Xianjun , Wang Fushun , Huang Jason H. 
Published: September 2021

Objective: The aim of the study is to investigate effects of loneliness on individual's mental health and the mediating effects of intolerance of uncertainty and sleep quality in the post Coronavirus-19 period, especially for the young people.Methods: The questionnaires used in this study include UCLA loneliness scale (UCLA-3), the Pittsburgh Sleep Quality Index (PSQI), intolerance for uncertainty (IU) and the Chinese version of DASS-21. A total number of 289 subjects were recruited in the study, which includes 209 females (72.3%), 80 males (27.7%); and 212 students (73.4%), 77 working staffs (26.6%).Results: The results showed that: (1) people have high levels of loneliness, anxiety, depression and stress, and poor sleep quality; (2) the mediating effect of intolerance for uncertainty in the relationship of loneliness and mental health is significant (effect size = 0.178, 95% CI confidence interval: [0.115, 0.241]), and the mediating effects of sleep quality in the relationship between loneliness and mental health is significant (effect size = 0.127, 95% CI confidence interval: [0.017, 0.239]).Conclusion: Loneliness invokes a stronger self-concerned inadaptability to threat response and may lead to more mental diseases through more serious intolerance for uncertainty and insomnia.
Impact of Oral Hygiene on Prognosis in Patients With Squamous Cell Carcinoma of the Lower Gingiva
Authors: Zhao Hui , Zhang Shengnan , Ma Jinji , Sun Xiaodong 
Published: September 2021

Objective: We aimed to analyze the significance of oral hygiene in patients with squamous cell carcinoma of the lower gingiva.Methods: Oral hygiene was assessed using a questionnaire by calculating the oral health (OH) score and the dental care (DC) score. The association of oral hygiene with clinical pathologic variables, disease free survival (DFS), and overall survival (OS) was analyzed.Results: Four out of 53 non-smokers and 19 out of 90 current or former smokers had an OH score of 6 (statistically significant difference, p = 0.036). Fifteen out of 63 patients with a T3/T4 tumor and 8 out of 80 patients with a T1/T2 tumor had an OH score of 6 (statistically significant difference, p = 0.026). Similar statistically significant findings were noted with respect to the DC scores, smoking status, and tumor stage. Among patients with an OH score of 0–5, the 5-year DFS and OS rates were 55 and 50%, respectively, and among patients with an OH score &gt;5, they were 46 and 43%, respectively (both differences statistically significant, p &lt; 0.05). Among patients with a DC score of 0–2, the 5-year DFS and OS rates were 69 and 51%, respectively and among patients with a DC score &gt;2, they were 50 and 47%, respectively (both differences statistically significant, p &lt; 0.05). Cox model confirmed OH and DC scores as independent factors affecting the DFS and OS.Conclusion: Poor oral hygiene was associated with decreased DFS and OS.
A Cross-Sectional Survey of the Knowledge, Attitudes, and Practices of Antimicrobial Users and Providers in an Area of High-Density Livestock-Human Population in Western Kenya
Authors: Kemp Steven A. , Pinchbeck Gina L. , Fèvre Eric M. , Williams Nicola J. 
Published: September 2021

Background: Antimicrobial resistance (AMR) is one of the most important global health crises in recent times and is driven primarily by antimicrobial consumption. In East Africa, there is a paucity of data regarding the knowledge, attitudes, and practices (KAP) related to antimicrobial use (AMU). We investigate the ways in which antimicrobial users in the veterinary sector accessed veterinary antimicrobials, and common behaviors of veterinary antimicrobial users and prescribers associated with AMU and AMR.Methods: In total, 70 farmers, staff at 49 agricultural-veterinary antimicrobial shops (agrovet staff) and 28 veterinary animal healthcare workers or veterinary surgeons (veterinary professionals) were interviewed in Busia county, western Kenya in 2016 using a standard questionnaire as a framework for structured interviews. Data recorded included participant demographics, level of education, access to and sources of veterinary antimicrobials, prescribing patterns, and knowledge of AMR and antimicrobial withdrawal periods.Results: The majority of antimicrobials were accessed through informal means, purchased from agroveterinary shops; more than half of staff did not hold nationally mandated qualifications to advise on or sell veterinary antimicrobials. Approximately 40% of veterinary antimicrobials were sold without a prescription and it was noted that both price and customer preference were important factors when selling antimicrobials in almost all agrovet shops. Knowledge of the dangers associated with AMR and AMU were mostly superficial. Treatment failure occurred often, and there was a lack of differentiation between AMR and simply treatment failure.Conclusion: In this study area in East Africa with high-density human and livestock populations, AMU was primarily for maintenance of livestock health. These findings have highlighted several aspects surrounding inappropriate access to antimicrobials, and as such require attention from policy makers concerned with AMR in both livestock and human medicine sectors. Improving prescribing practices and ensuring a minimum level of general education and awareness of prescribers, as well as expanding the role of agrovet staff in antimicrobial stewardship programmes, may help begin to mitigate the maintenance and transmission of AMR, particularly amongst livestock.