bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with Fragile X Syndrome
Authors: Perche Olivier , Lesne Fabien , Patat Alain , Raab Susanne , Twyman Roy , Ring Robert H. , Briault Sylvain
Published: April 2021

Background: Disturbances in sensory function are considered as an important clinical feature of individuals with neurodevelopmental disorders such as Fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS, thus elevating interest in sensory function as a clinical target for therapeutics development. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1-/y genetic mouse model of FXS. The goals of this study were two-fold: 1) assess the feasibility of measuring ERG and CS as a biomarker in individuals with FXS, and 2) investigate whether the deficits in ERG and CS originally discovered in Fmr1-/y mice were translatable to humans with FXS. Methods: Both ERGs and CS were measured in a cohort of individuals with FXS (n=20, 18-45 yrs) and age-matched healthy controls (n=20, 18-45 yrs). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full field flash ERG device (RETeval®, LKC Technologies Inc, Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). Results: Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1-/y genetic mouse model of FXS, abnormalities in both ERG waveform and CS were observed in FXS. Conclusions: This study demonstrates the feasibility of using ERG and CS for assessing the visual system in FXS and establishes the translatability of the Fmr1-/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complimentary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS.Trial Registration: ID-RCB number 2019-A01015-52 registered on the 05/17/2019.
Transcranial direct-current stimulation protects against cerebral ischemia-reperfusion injury through regulating Cezanne-dependent signaling
Authors: Cheng Jing , Fan Yan-Qin , Jiang Hong-Xiang , Chen Song-Feng , Chen Juan , Liao Xin-Yu , Zou Ying-Ying , Lan Hai-yang , Cui Yu , Chen Zhi-Biao , Chen Qianxue , Wan Qi
Published: April 2021

Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.
A Silent Epidemic of Gross Congenital malformations in Tigray, Northern Ethiopia: Hospital-Based Study
Authors: Mekonen Hayelom , Berhe Yibrah , Berihu Birhane Alem , Teka Hale , Hadgu Abera , Gebregziabher Letekirstos , Halefom Etenat , Magana Tony , Mulugeta Afework
Published: April 2021

Background

Congenital malformations are defects of the morphogenesis of organs or body during the pregnancy period and are identifiable at pre- or postnatal. It is identified as the major cause of child mortality worldwide. There is a need to understand the prevalence of congenital malformations in Tigray in particular and Ethiopia in general as surveillance data are lacking. Hence, this study was designed to investigate the burden of gross congenital malformations in the Tigray Region, Northern Ethiopia.
Methods

This cross-sectional study was conducted of birth outcomes diagnosed with structural malformations in the labor ward admitted to Ayder comprehensive specialized university hospital and five general hospitals namely Alamata, Lemlem Karl, Adwa, St Mary and Shul Hospitals from Tigray region between January 2018 and January 2019. Data on demographic and clinical findings of the mothers and their pregnancy outcomes were collected using a standard data collection tool. Simple descriptive statistics were used to characterize the study subjects. Statistical analysis was done using chi-square analysis and P value < 0.05 was considered significant.
Results

A total of 12225 births were recorded in the six hospitals during the study period. Of these, 383 births had gross congenital malformations of different degrees of severity and 12 of them were stillbirths. The overall occurrence of congenital malformations was 3.1 % of the total births (live births and stillbirths) examined. Central nervous system anomaly mainly Neural tube defect were found the commonest anomalies observed in this study. The maternal factors (maternal age, gravidity, abortion history, parity) and fetal factors (birth weight and gestational ages were significantly associated with the occurrence of the gross congenital malformations (p < 0.05).
Conclusion

This study has shown a high prevalence of gross congenital anomalies exists in the study communities. High prevalence of central nervous system-related malformations was observed in the Tigray region, given the high prevalence of nutritional deficiency and lack of periconceptional care that can impact the formation of the nervous system in the current study population. Hence, there should be an immediate food fortification with folic acid and periconceptional folic acid supplementation for all reproductive-age women in the region and the country at large.
Health-related quality of life in women with breast cancer: A review of measures
Authors: Salas Maribel , Mordin Margaret , Castro Colleen , Islam Zahidul , Tu Nora , Hackshaw Michelle D
Published: April 2021

Objective: To identify and describe the breast cancer–specific health-related quality of life (HRQoL) instruments with evidence of validation in the breast cancer population for potential use in patients treated for breast cancer (excluding surgery). Methods: We conducted a systematic literature review using PubMed, Embase, and PsycINFO databases to identify articles that contain psychometric properties of HRQoL instruments used in patients with breast cancer. Relevant literature from January 1, 2009, to August 19, 2019, was searched. Articles published in English that reported psychometric properties (reliability, validity) of HRQoL instruments were identified.Results: The database search yielded 613 unique records; 131 full-text articles were reviewed; 80 articles presented psychometric data for instruments used in breast cancer. This article focuses on the 33 that described psychometric properties of breast cancer–specific HRQoL instruments. Twelve breast cancer–specific HRQoL instruments were identified and reviewed: EORTC QLQ-C30, EORTC QLQ-BR23, FACT-B, FBSI, NFBSI-16, YW-BCI36, BCSS, QuEST-Br, QLICP-BR, INA-BCHRQoL, and two newly developed unnamed measures, one by Deshpande and colleagues (for use in India) and one by Vanlemmens and colleagues (for use among young women and their partners). The articles that described the EORTC QLQ-C30, QLQ-BR23, and FACT-B centered on validating translations, providing additional support for content validity, and demonstrating acceptability of electronic patient-reported outcome administration. Psychometric properties of the measures were acceptable. Several new measures have been developed in Asia with an emphasis on development on cultural relevance/sensitivity. Others focused on specific populations (i.e., young women with breast cancer). Conclusions: Historically, there have been limited options for validated measures to assess HRQoL of patients with breast cancer. A number of new measures have been developed and validated, offering promising options for assessing HRQoL in this patient population. This review supports the reliability and validity of the EORTC QLQ-C30 and FACT-B; new translations and electronic versions of these measures further support their use for this population.
A cross-sectional study on the guideline adherence to antiemetic regimens for chemotherapy-induced nausea and vomiting: A single center retrospective study of 1000 patients.
Authors: Luo Cong , Chen Lei , Xu Qi , Li Jingjing , Wei Qing , Shang Mingge , Ying Jieer
Published: April 2021

Background

Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in patients who undergoing chemotherapy, it is very important to control CINV to maintain dose intensity and patients' quality of life. To analyze the current situation of CINV for the tumor patients who undergoing chemotherapy, we used a cross-sectional survey to assess CINV status in those patients, and whether the drugs used by doctors in each department met the guidelines, and compared the incidence of acute and delayed CINV overall post-chemotherapy periods.

Methods

This was a single-center, cross-sectional retrospective study of patients with chemotherapy discharged from different departments of Zhejiang Cancer Hospital in China. Participants reported the occurrence, severity, and impact on daily life of nausea and vomiting from the day of chemotherapy administration up to 5 days, and physicians collected the clinical data from the medical records.

Results

Data were collected from 875 responses totally. In this study, the overall incidence rate of CINV was 44.34%, acute CINV was 24.57%, and delayed CINV was 39.66%. 19.89% patients had both acute and delayed CINV. The consistency rates of antiemetic with guideline in different departments showed significant gap between the actual usage of drugs and the recommended guidelines (P=0.001). In 875 patients, 518 patients received guideline recommended antiemetic regimen, the CINV rates of complete control (CC), defined as the absence of any symptoms, were 61.58%. While the CC rates in other 357 patients were 47.06%(P<0.001).

Conclusion

Overall, clinician adherence to antiemetic guideline recommendations in different departments remained poorly characterized with varying degrees. Future studies should focus on the complete rate as a primary end point rather than complete remission. The standardized management of CINV in patients need to be further strengthened and doctors need to use drugs more regularly to reduce the occurrence of CINV in patients.
Effect of matcha consumption on gut microbiota in healthy Japanese individuals: study protocol for a double-blind crossover interventional study
Authors: Takegami Maya , Hashimoto Yoshitaka , Miyoshi Tomoki , Munekawa Chihiro , Yoshimura Takashi , Nakajima Hanako , Kimura Tomonori , Okamura Takuro , Nakanishi Naoko , Kitao Yuki , Kinoshita Kazutsugu , Hamaguchi Masahide , Fukui Michiaki
Published: April 2021

Background: This study compares and clarifies the changes in intestinal flora resulting from the continuous consumption of two types of matcha.Methods: Healthy adults will consume two types of matcha tea for four weeks, and differences in the intestinal microflora before and after drinking will be compared. Gut microbiota will be identified using next-generation sequencing (NGS). Phylogenetic classification of the enterobacteria will be performed based on sequence similarities. The relative proportions of the classified enterobacteria to the total nucleotide sequences will be compared between the samples obtained from the two groups consuming different matcha.Discussion: The continuous consumption of matcha may improve dysbiosis and prevent atherosclerosis. The effects may vary according to the type of matcha used.Trial registration:The study was registered with university hospital medical information network (UMIN) (UMIN000040303), and all participants gave their written informed consent. Registered 1 November 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045982.
Longitudinal Study on the Impact of Three Major Regulations on the Korean Pharmaceutical Industry in the Last 30 Years
Authors: Um Seung In , Sohn Uy Dong , Jung Sun-Young , You Seung-Hun , Kim Changone , Lee Sora , Lee Heesang
Published: April 2021

Background: The pharmaceutical industry is heavily regulated. Partly for this reason, new drugs generally take over ten years to reach market entry from the product development stage. Although regulations affect the pharmaceutical industry over a long time, extant studies have usually focused on the short period before and after implementing a new regulatory policy to determine the impact of that policy. The purpose of this study is to examine whether and how significant regulatory policies affect long-term innovation in the pharmaceutical industry in Korea.Methods: This study focused on three significant regulatory policies: the product patent system, changes in the Good Manufacturing Practice (GMP) system, and the Drug Expenditure Rationalization Plan (DERP). This study used Interrupted Time Series (ITS) analysis to investigate the policies' long-term impacts before and after their implementation.Results: Our results show that the introduction of the product patent system in 1987 significantly increased the number of Korean patent applications. The revised GMP policies' effect was also statistically significant, both before and after implementation and between preemptive companies and non-preemptive ones. The DERP, however, did not significantly delay new drug registration in Korea due to companies' negotiations with the regulatory authorities or the system that links drug approval and price evaluation.Conclusion: This study showed that the policies of the product patent system, GMP policies, and DERP regulations have significantly altered the course of the pharmaceutical industry in Korea. This study suggests that it is necessary for companies to preemptively respond to systemic changes in development and production strategies to deal with regulatory changes and achieve sustainable growth. Also, this study implies that the governmental authorities need to develop a regulatory policy that links innovation and competitiveness in domestic pharmaceutical companies.
Effect of paclitaxel-coated balloon angioplasty on side branch lesion and cardiovascular outcomes in patients with de novo true coronary bifurcation lesions undergoing percutaneous coronary intervention
Authors: Li Youmei , Mao Qi , Liu Huanyun , Zhou Denglu , Zhao Jianhua
Published: April 2021

Purpose
To compare the effects of paclitaxal-coated balloon (PCB) versus conventional balloon (CB) on side branch (SB) lesion and cardiovascular outcomes in patients with de novo true bifurcation lesions.
Methods
In total, 219 patients with de novo true bifurcation lesions were enrolled and divided into PCB group (102 cases) and CB group (117 cases) according to angioplasty strategy in SB. Drug-eluting stent (DES) was implanted in main vessel (MV) for each subject. All subjects underwent a 12-month follow-up for late lumen loss (LLL), restenosis and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). MACEs included cardiac death, nonfatal myocardial infarction and angina pectoris.
Results
There were no differences in diameter, minimum lumen diameter (MLD) and stenosis for bifurcation lesions between the two groups before and immediately after PCI (P > 0.05). After 12-month follow-up, no differences occurred in MV-MLD and MV-LLL between the two groups (P > 0.05); SB-MLD in PCB group was higher than that in CB group (1.97 ± 0.36 mm vs. 1.80 ± 0.43 mm, P = 0.007); SB-LLL in PCB group was lower than that in CB group (0.11 ± 0.18 mm vs. 0.19 ± 0.25 mm, P = 0.024). Multivariate COX analyses indicated that PCB group had lower MACE risk than CB group (HR = 0.480, 95%CI 0.244–0.941, P = 0.033).
Conclusion
PCB could decrease SB-LLL and MACE risk in patients with de novo true coronary bifurcation lesion 12 months after single-DES intervention.
Use of an electronic medication management support system in patients with polypharmacy in general practice: study protocol of a quantitative process evaluation of the AdAM trial
Authors: Brünn Robin , Lemke Dorothea , Chapidi Kiran , Köberlein-Neu Juliane , Piotrowski Alexandra , Söling Sara , Greiner Wolfgang , Kellermann-Mühlhoff Petra , Timmesfeld Nina , Akker Marjan van den , Muth Christiane
Published: April 2021

Background: Much research is currently devoted to polypharmacy, but interventional studies often fail to significantly improve patient-relevant outcomes or just measure surrogate parameters. Interventions and their settings are often complex, and a wide range of factors affect results. The aim of the AdAM study is to reduce hospitalization and death by requiring general practitioners (GPs) to use a computerized decision-support system (CDSS). The study will undergo a process evaluation to identify relevant factors for successful implementation and to assess whether the intervention was implemented as intended.Research questions: We will assess implementation (reach, fidelity, dose, tailoring) by asking the following questions: (1) Who took part in the intervention, i.e., the proportion of GPs that used the CDSS, and the proportion of patients that were enrolled by them? Information on the characteristics of GPs and patients will also be collected. (2) How many and what type of medication alerts were handled by the GPs? (3) Was the intervention implemented as intended? (4) On what days did GPs use the intervention tool? We will conduct subgroup analyses to all questions, including time effects to account for software improvements over time.Methods: The process evaluation is part of a stepped wedge cluster-randomized controlled trial. Characteristics of practices, GPs and patients using the CDSS will be compared with the non-participating population. CDSS log data will be analyzed to evaluate how the number of medication alerts changed between baseline and two months later and identify the kind of medication alerts that are given highest priority. The comparison of enrolled patients on weekdays vs weekends will shed light on whether GPs use the CDSS in the absence or presence of patients. All outcomes will be presented using descriptive statistics, and significance tests will be used to identify any associations between them.Discussion: This study protocol is the basis for conducting the analyses of the log data-based process evaluation. By providing insight into the way GPs conduct medication reviews, the evaluation will provide a context to the trial results and support their interpretation. The evaluation relies on the proper documentation of what the CDSS was used for, which may limit its explanatory power.Trial registration: ClinicalTrials.gov, NCT03430336. Registered on February 6, 2018. https://clinicaltrials.gov/ct2/show/NCT03430336
Inhibition of β-catenin Protects Mouse Hearts From Ventricular Arrhythmias After Myocardial Infarction Independent of Ion Channel Gene Changes
Authors: Wang Jerry , Xia Ying , Lu Aizhu , Wang Hongwei , Davis Darryl R. , Liu Peter , Beanlands Rob S. , Liang Wenbin
Published: April 2021

The Wnt/β-catenin signaling regulates ion channel gene expressions in cardiomyocytes. Because Wnt/β-catenin signaling is activated in myocardial infarction (MI), this study aims to investigate if β-catenin inhibition affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in wild-type (WT) and cardiomyocyte-specific β-catenin knockout (KO) mice. KO mice showed reduced susceptibility to VT (18% vs. 77% in WT) at week-8 after MI, associated with attenuated structural remodeling (reduced scar size and attenuated left ventricle dilation) as compared to WT. However, at the subacute phase (week-1) and chronic phase (week-8) after MI, Wnt/β-catenin signaling activation was found in non-cardiomyocytes, but not in cardiomyocytes. Downregulations of Scn5a (encoding Nav1.5) and Gja1 (encoding Cx43) were found at week-1 but not at week-8, while downregulations of K+ channel genes were present at both week-1 and -8. Consistent with no activation of Wnt/β-catenin pathway in cardiomyocytes at week-1 and -8, these alterations in ion channel/transporter genes were not different between KO and WT mice. This study demonstrated that mice with cardiomyocyte-specific β-catenin deletion have reduced VT susceptibility after MI which is caused by attenuated structural remodeling, instead of alterations in ion channel gene expressions.
Manganese distribution in the Mn-hyperaccumulator Grevillea meisneri from New Caledonia
Authors: Bihanic Camille , Petit Eddy , Perrot Roseline , Cases Lucie , Garcia Armelle , Pelissier Franck , Poullain Cyril , Rivard Camille , Hossaert Martine , Grison Claude
Published: April 2021

• Grevillea meisneri, an endemic New Caledonian Mn-hyperaccumulator, is used in rehabilitation of degraded mining sites on the island. Large-scale programs require transplanting nursery-grown seedlings, but effects of the nursery environment on Mn tolerance of transplants and their capacity to hyper-accumulate Mn are unknown, slowing rehabilitation efforts.• We studied tissue-level distribution of Mn and other elements in different tissues of G. meisneri using micro-X-Ray Fluorescence spectroscopy (μXRF), comparing nursery-grown plants transplanted into the site and sampled seven years later, and similar-sized plants that had grown spontaneously in the site. • Mirroring patterns in other Mn-hyperaccumulators, Mn was preferentially accumulated in leaves but was also present in roots. Concentrations were highest in leaf epidermal tissues, in cortex and vascular tissues of stems and primary roots, and in phloem and pericycle-endodermis of parent cluster roots. Although abundant in soil, Ni was absent from all tissues of G. meisneri. Ca was always co-localised with Mn. Preferential uptake of Mn vs Ni in roots implies as-yet-uncharacterized specific Mn-transporters, while Ca and Mn co-localisation suggests shared transport pathways. • No differences were observed in concentration and distribution of Mn in transplanted and spontaneously-growing plants. Nursery-grown transplants should be highly suitable for large-scale, high-throughput rehabilitation programs.
Handwork Vs Machine; A Comparison of Rheumatoid Arthritis Patient Populations as Identified From Ehr Free-text by Diagnosis Extraction Through Machine-learning or Traditional Criteria-based Chart Review
Authors: Maarseveen Tjardo , Maurits Marc , Niemantsverdriet Ellis , Mil Annette van der Helm - van , Huizinga Thomas W.J. , Knevel Rachel
Published: April 2021

BackgroundElectronic Health Records (EHRs) offer a wealth of observational data. Machine-Learning (ML) methods are efficient at data extraction, capable of processing the information-rich free-text physician notes in EHRs. The clinical diagnosis contained therein represents physician expert opinion and is more consistently recorded than classification criteria components.ObjectivesTo investigate the overlap and differences between Rheumatoid Arthritis patients as identified either from EHR free-text through extraction of the rheumatologist diagnosis using machine-learning (ML) or through manual chart-review applying the 1987 and 2010 RA classification criteria.MethodsSince EHR initiation, 17,662 patients visited the Leiden outpatient clinic. For ML, we used a Support Vector Machine (SVM) model to identify those who were diagnosed with RA by their rheumatologist. We trained & validated the model on a random selection of 2,000 patients, balancing PPV and Sensitivity to define a cutoff, and assessed performance on a separate 1,000 patients. We then deployed the model on our entire patient selection (including the 3,000). Of those, 1,212 patients had both a 1987 and 2010 EULAR/ACR criteria status at one year after inclusion into the local prospective arthritis cohort. In these 1,212 patients we compared the patient characteristics of RA cases identified with ML and those fulfilling the classification criteria. ResultsThe ML model performed very well in the independent test set (sensitivity=0.85, specificity=0.99, PPV=0.86, NPV=0.99). In our selection of patients with both EHR and classification information, 406 were recognized as RA by ML and 386 and 457 fulfilled the 1987 or 2010 criteria respectively. Eighty percent of the ML-identified cases fulfilled at least one of the criteria sets. Both demographic and clinical parameters did not differ between the ML extracted cases and those identified with EULAR/ACR classification criteria. ConclusionsWith ML methods we enable fast patient extraction from the huge EHR resource. Our ML algorithm accurately identifies patients diagnosed with RA by their rheumatologist. This resulting group of RA patients had a strong overlap with patients identified using the 1987 or 2010 classification criteria and the baseline (disease) characteristics were comparable. ML assisted case labelling enables high-throughput creation of inclusive patient selections for research purposes.
Efficacy of Lenvatinib for Unresectable Hepatocellular Carcinoma Based on Background Liver Disease Etiology: Multi-center Retrospective Study
Authors: Hiraoka Atsushi , Kumada Takashi , Tada Toshifumi , Tani Joji , Kariyama Kazuya , Fukunishi Shinya , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Kawata Kazuhito , Yasuda Satoshi , Toyoda Hidenori , Aoki Tomoko , Tanaka Takaaki , Ohama Hideko , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Arai Taeang , Okubo Tomomi , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Joko Koji , Hiasa Yoichi , Kudo Masatoshi
Published: April 2021

Background/Aim: Hepatocellular carcinoma patients (HCC) related with non-alcoholic steatohepatitis (NASH) has been recently reported to be not responsive to immune-checkpoint inhibitor treatment (ICI). This study aimed to evaluate therapeutic efficacy in non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC) treated with lenvatinib.Material/Methods: Five-hundred-thirty u-HCC with Child-Pugh A were enrolled, and divided into the NAFLD/NASH (n=103) and Viral/Alcohol (n=427) groups. Clinical features were compared in a retrospective manner.Results: Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P=0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P=0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated AFP (≥400ng/mL) (HR1.294, P=0.014), elevated ALT (≥30 U/L) (HR1.247, P=0.029), modified ALBI grade 2b (HR1.236, P=0.047), and NAFLD/NASH etiology (HR0.763, P=0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.750, P=0.076), whereas AFP (≥400ng/mL) (HR1.402, P=0.009), later line use (HR0.737, P=0.0137), BCLC C stage (HR1.297, P=0.035), and modified ALBI grade 2b (HR1.875, P<0.001) were significant.Conclusion: ICI is reportedly not effective for NAFLD/NASH-related HCC, while lenvatinib can improve the prognosis of u-HCC irrespective of HCC etiology or its line of treatment.
Prediction Models for Energy Consumption and Surface Quality in Stainless Steel Milling
Authors: Yu Shuo , Zhao Guoyong , Li Chunxiao , Xu Shuang , Zheng Zhifu
Published: April 2021

Stainless steel is a kind of difficult-to-machine material, and the work hardening in milling easily leads to high energy consumption and poor surface quality. Thus, the influence of machined surface hardness on energy consumption and surface quality cannot be ignored. To solve this problem, the prediction models for machine tool specific energy consumption and surface roughness are developed with tool wear and machined surface hardness considered firstly. Then, the validity of the models is verified through AISI 304 stainless steel milling experiments. The results show that the prediction accuracy of the machine tool specific energy consumption model can reach 98.7%, and the roughness model can reach 96.8%. Later, according to the developed prediction models, the influence of milling parameters, surface hardness, and tool wear on the machine specific energy consumption and surface roughness is studied. Results show that in stainless steel milling, the most significant parameters for surface roughness is the machined surface hardness, while that for energy consumption is the feed per tooth. The machine specific energy consumption increases linearly with the increase of the tool wear and the machined surface hardness gradually. The proposed models are helpful to optimize the process parameters for high efficiency and high quality machining of stainless steel.
Deep Learning for Early Dental Caries Detection in Bitewing Radiographs
Authors: Lee Shinae , Oh Sang-il , Jo Junik , Kang Sumi , Shin Yooseok , Park Jeong-won
Published: April 2021

The early detection of incipient dental caries enables preventive treatment, and bitewing radiography is a good diagnostic tool for posterior incipient caries. In the field of medical imaging, the utilization of deep learning with convolutional neural networks (CNNs) to process various types of images has been actively researched and has shown promising performance. In this study, we developed a CNN model using a U-shaped deep CNN (U-Net) for dental caries detection on bitewing radiographs and investigated whether this model can improve clinicians’ performance. In total, 304 bitewing radiographs were used to train the deep learning model and 50 radiographs were used for performance evaluation. The diagnostic performance of the CNN model on the total test dataset was as follows: precision, 63.29%; recall, 65.02%; and F1-score, 64.14%, showing quite accurate performance. When three dentists detected dental caries using the results of the CNN model as reference data, the overall diagnostic performance of all three clinicians significantly improved, as shown by an increased recall ratio (D1, 85.34%; D1', 92.15%; D2, 85.86%; D2', 93.72%; D3, 69.11%; D3', 79.06%). These increases were especially significant in the incipient and moderate caries subgroups. The deep learning model may help clinicians to diagnose dental caries more accurately.
An Improved Calibration and Uncertainty Analysis Approach Using a Multicriteria Sequential Algorithm for Hydrological Modeling
Authors: Wu Hongjing , Chen Bing , Ye Xudong , Guo Huaicheng , Meng Xianyong , Zhang Baiyu
Published: April 2021

Hydrological models are widely used as simplified, conceptual, mathematical representatives for water resource management. The performance of hydrological modeling is usually challenged by model calibration and uncertainty analysis during modeling exercises. In this study, a multicriteria sequential calibration and uncertainty analysis (MS-CUA) method was proposed to improve hydrological modeling efficiency and performance with high reliability. To evaluate the performance, the proposed MS-CUA method was applied to two case studies comparing two traditional methods: sequential uncertainty fitting algorithm (SUFI-2) and generalized likelihood uncertainty estimation (GLUE). The results indicated that the MS-CUA method can quickly locate the highest posterior density (HPD) regions of parameters to improve computational efficiency. It also provided better-calibrated results and more balanced uncertainty analysis results comparing with other traditional methods.
Signatures based on tumor microenvironment genes can reliably predict the prognosis of laryngeal cancer patients
Authors: Ren Haitang , Luo Zheng , Wang Min , Chen Lei , Zhang Bo
Published: April 2021

Purpose: To develop a tumor microenvironment (TME) related genes based prognostic model for laryngeal cancer patients risk prediction. Methods: A innovative prognosic model was generated based on TME related genes (760 genes). Based on the model, laryngeal cancer patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio as well as checkpoints have been exploreds. Results: It can be shown here 15 genes demonstrate significant differences, which can better predict laryngeal cancer patient prognosis. The accuracy of the model prediction is evaluated and approved by the AUC value. From the immune cell infiltration ratio analysis, there is a significant difference in the infiltration degree of several types of immune cells and 6 immune checkpoints between high and low-risk laryngeal cancer patients. At the same time, the close related genes as well as TME pathways have been also investigated. Conclusion: This study has explored a potential prognostic biomarker and developed a novel TME-associated prognostic model for laryngeal cancer, which provides a valuable reference for future clinical research.
The extent of honeycombing on computed tomography cannot predict the treatment outcome of patients with acute exacerbations of interstitial lung disease (Retrospective cohort study)
Authors: Nishikawa Yurika , Hara Yu , Tagami Yoichi , Nagasawa Ryo , Murohashi Kota , Aoki Ayako , Tanaka Katsushi , Watanabe Keisuke , Horita Nobuyuki , Kobayashi Nobuaki , Yamamoto Masaki , Kudo Makoto , Kaneko Takeshi
Published: April 2021

Background: The purpose of this retrospective study was to clarify whether the presence of honeycombing on computed tomography (CT) can affect the prognosis of patients with acute exacerbations (AEs) of interstitial lung diseases (ILDs).Methods: Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, and 3-month mortality were retrospectively compared between the CT honeycombing present and absent groups at the diagnosis of AEs of ILDs.Results: Ninety-five patients who were on corticosteroid pulse therapy were assessed. Though log-rank tests showed that Kaplan-Meier survival curves of the high and low ground-glass opacity (GGO) score groups differed significantly in 3-month mortality in patients with AEs of idiopathic ILDs (P = 0.007) and overall patients (P = 0.045), there was no significant difference between the CT honeycombing present and absent groups in patients with AEs of idiopathic ILDs (P = 0.600) and AEs of secondary ILDs (P = 0.472), as well as of overall patients (P = 0.905). In addition, whereas CCIS (OR, 1.436; 95% CI, 1.119-1.938; P = 0.004) and age (OR, 1.097; 95% CI, 1.119-1.212; P = 0.026) were significant predictors of 3-month mortality in the CT honeycombing absent group, serum lactate dehydrogenase (OR, 1.004; 95% CI, 1.002-1.007; P = 0.001) and sex (OR, 6.381; 95% CI, 0.821-49.602; P = 0.023) were significant predictors in the CT honeycombing present groupConclusions: The clinical features of patients with or without honeycombing may differ due to the difference in prognostic factors, but these groups were found to have similar prognoses 3 months after AE onset, and clinicopathological examinations according to these groups are essential.
Physicians’ experiences, attitudes, and beliefs towards medical cannabis: a systematic literature review
Authors: Rønne Sabrina Trappaud , Rosenbaek Frederik , Pedersen Line Bjørnskov , Waldorff Frans Boch , Nielsen Jesper Bo , Riisgaard Helle , Søndergaard Jens
Published: April 2021

Background: An increasing number of countries legalise the use of medical cannabis or allow it for a narrow range of medical conditions in patients. Physicians, and often the patients’ general practitioner, play a major role in the implementation of this policy, but many of them perceive a lack of evidence-based knowledge and may not be confident with providing patients with medical cannabis. The objectives of this review are to synthesise findings about hospital physicians’ and GPs’ experiences, attitudes, and beliefs towards the use of medical cannabis with the purpose of identifying barriers and facilitators towards providing it to their patients.Methods: Peer-reviewed articles addressing hospital physicians’ and GPs’ experiences, attitudes, and beliefs towards the use of medical cannabis were searched systematically in PubMed, Scopus, EMBASE, and the Cochrane Library.Results: Twenty-one articles were included from five different countries in which the medical cannabis laws varied. The studied physicians experienced frequent inquiries about medical cannabis from their patients (49-95%), and between 10-95% of the physicians were willing to provide it to the patients, depending on setting, specialty and experience among the physicians. This review found that physicians experienced in prescribing medical cannabis were more convinced of its benefits and less worried about adverse effects than non-experienced physicians. However, physicians specialized in addiction treatment and certain relevant indication areas seemed more sceptical compared to physicians in general. Nevertheless, physicians generally experienced a lack of knowledge of clinical effects including both beneficial and adverse effects.Conclusion: This review indicates that hospital physicians and GPs’ in various specialties frequently experience patient demands for medical cannabis and to some degree show openness to using it, although there was a wide gap between studies in terms of willingness to provide. Hospital physicians and GPs’ experienced in prescribing are more convinced of effects and less worried of adverse effects. However, most physicians experience a lack of knowledge of beneficial effects, adverse effects and of how to advise patients, which may comprise barriers towards prescribing. More research, including larger studies with cohort designs and qualitative studies, is needed to further examine facilitators and barriers to physicians’ prescribing practices.
Genetic Analysis of the ZNF804A Gene in Mexican Patients With Schizophrenia, Schizoaffective Disorder and Bipolar Disorder 
Authors: ANGUIANO LUCIA MUNCH , Camarena Beatriz , Nieto-Quinto Jesica , Torre Patricia de la , Laclette Juan Pedro , Hirata-Hernandez Harumi , Hernández-Muñoz Sandra , Aguilar-Garcia Alejandro , Becerra-Palars Claudia , Gutierrez-Mora Doris , Ortega-Ortiz Hiram , Escamilla-Orozco Raul , Saracco-Alvarez Ricardo , Bustos-Jaimes Ismael
Published: April 2021

Background: Evidence suggests that Schizophrenia (SCZ), Schizoaffective Disorder (SAD) and Bipolar Disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. The aim was to analyze the rs1344706 SNP and identify common and rare variants in a targeted region of the ZNF804A gene in SCZ, BPD and SAD Mexican patients compared with a control group.Methods: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. An additional sample of 167 patients and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene. Results: We replicated the association between the rs1344706 and SCZ, SAD and BPD. In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between SCZ, SAD and BPD did not show statistical differences. Conclusions: Our findings support the evidence suggesting that ZNF804A gene is involved in the etiology of SZC, SAD and BPD. Future studies are needed to identify the pleiotropic effect of this gene in psychiatric disorders.
Infrared Thermography for Assessment of Thoracic Paravertebral Block: A Prospective Observational Study
Authors: Zhang Shuang , Liu Yong , Liu Xiaohu , Liu Tianzhu , Li Pengcheng , Mei Wei
Published: April 2021

Background: There was no “gold standard” to assess the success or failure of thoracic paravertebral block (TPVB). Measurement of skin temperature with infrared thermography (IT) would be a reliable method to evaluate the effectiveness of regional blocks. This study aimed to explore the feasibility of using skin temperature difference (Td) determined by IT between the blocked and unblocked side to predict the outcome of TPVB. Methods: Sixty-one patients undergoing elective unilateral breast or thoracoscopic surgery were enrolled in this prospective observational study. TPVB was performed at T4 and T5 under real-time ultrasound guidance with 10 mL of 0.4% ropivacaine for each patient, respectively. Td between the blocked and unblocked side were measured with IT from T2 to T10 at the anterior chest wall before TPVB and 5 min, 10 min, 15 min and 20 min after TPVB. Pinprick test was performed at 20 min after TPVB. Successful TPVB was defined as no sensation to pinprick in 3 or more adjacent dermatomes corresponding to the site of injection at 20 min after TPVB. Td was compared to pinprick test for evaluating its effectiveness in predicting the success of TPVB. The sensitivity, specificity, and cut-off value of Td for predicting successful TPVB were determined by receiver operator characteristic (ROC) curve analysis.Results: Compared with the baseline value before block, Td from T2 to T10 were significantly increased at each time point in successful blocks. In failed blocks, Td was not increased in any dermatome. The increase of Td at T4-T7 was more than 1℃ 20 min after successful TPVB. Fifteen minutes after block, Td increase at T4 had the greatest potential to predict block success. The area under the ROC curve was 0.960 at a cut-off value of 0.63℃ with a sensitivity of 83.3% and a specificity of 100.0%.Conclusions: This study suggested that the increase of Td at T4 dermatome determined by IT between the blocked and unblocked side is an early, quantitative, and reliable predictor of successful TPVB. Clinical trial registration: NCT04078347
Promotion of wound healing by insulin-like growth factor-1-loaded Bombyx mori L. silk fibroin films in diabetic mice
Authors: Lin Meng-Jin , Lu Mei-Chun , Chan Yun-Chen , Chang Hwan-You
Published: April 2021

This study aimed to engineer an advanced wound-dressing combining Bombyx mori L. silk fibroin (SF) with insulin-like growth factor-1 (IGF-1). Silk fibroin was purified through a newly-developed high-temperature degumming process and cast on a hydrophobic surface to form SF-films. The process allowed the fabrication of a film exhibiting a 42% increase in transparency and a 32% higher proliferation rate of BALB/3T3 fibroblasts compared to that obtained by conventional alkaline treatment. This study demonstrated that the optimal concentration of IGF-1 to promote BALB/3T3 cell growth in hyperglycemic medium was approximately 130 nM. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol IGF-1 showed significantly superior wound closure (13% increase) at 13 days after treatment compared to treatment with 65 pmol free IGF-1. We clearly observed improvement in diabetic wound healing exerted synergistically by SF-film and IGF-1, as reflected by parameters including degree of re-epithelialization, epithelial tissue area, and angiogenesis. These results strongly suggest the great potential of IGF-1-loaded SF-film as a dressing for the treatment of diabetic wounds.
An Advanced Extremum Seeking Scheme for the Target Trajectory in Electromagnetic Micromirror System
Authors: Sun Wanyan , Tan Yonghong
Published: April 2021

Now two problems result in bad control in the development of the electromagnetic micromirror system. One is that theoretical model in electromagnetic micromirror system is difficult to be determined; Another is that parameters in common control need to be tuned according to the experience. In this paper, cost function concept is proposed to determine the model order in slow-scan axis control of the electromagnetic micromirror. Then recursive least square scheme is built to off-line identify this model. Furthermore, an advanced extremum seeking scheme along with backtracking line search is exploited, which can automatically identify the best parameter value before each extremum search to improve the controllability based on this model for the target trajectory in slow-scan axis control. And the convergence of it is proved. Finally, the experiments and the simulations verify this method proposed valid.
Hypoxia-induced Preadipocyte factor 1 expression in human lung fibroblasts through ERK/PEA3/c-Jun pathway
Authors: Cheng Wun-Hao , Chen Chia-Ling , Chen Jing-Yun , Lin Chien-Huang , Chen Bing-Chang
Published: April 2021

Background
Several studies have reported that hypoxia plays a pathological role in severe asthma and tissue fibrosis. Our previous study showed that hypoxia induces A disintegrin and metalloproteinase 17 (ADAM17) expression in human lung fibroblasts. Moreover, preadipocyte factor 1 (Pref-1) is cleaved by ADAM17, which participates in adipocyte differentiation. Furthermore, Pref­1 overexpression is involved in liver and heart fibrosis. Studies have demonstrated that polyoma enhancer activator 3 (PEA3) and activator protein 1 (AP-1) play crucial roles in lung fibrosis, and the Pref-1 promoter region contains PEA3 and AP-1 binding sites, as predicted. However, the roles of extracellular signal-regulated kinase (ERK), PEA3, and AP-1 in hypoxia-stimulated Pref-1 expression in human lung fibroblasts remain unknown.
Methods
The protein expression in ovalbumin (OVA)-induced asthmatic mice was performed by immunohistochemistry and immunofluorescence. The protein expression or the mRNA level in human lung fibroblasts (WI-38) was detected by western blot or quantitative PCR. Small interfering (si) RNA was used to knockdown gene expression. The collaboration with PEA3 and c-Jun were determined by coimmunoprecipitation. Translocation of PEA3 from the cytosol to the nucleus was observed by immunocytochemistry. The binding ability of PEA3 and AP-1 to Pref-1 promoter was assessed by chromatin immunoprecipitation.
Results
Pref-1, PEA3, and hypoxia-inducible factor 1α (HIF-1α) were expressed in the lung sections of ovalbumin-treated mice. Hypoxia induced Pref­1 protein upregulation and mRNA expression in human lung fibroblasts (WI­38 cells). Moreover, PEA3 small interfering (si) RNA decreased the expression of hypoxia-induced Pref­1 in WI­38 cells. Hypoxia induced PEA3 phosphorylation, translocation of PEA3 from the cytosol to the nucleus, PEA3 recruitment and AP-1 binding to the Pref­1 promoter region, and PEA3-luciferase activity. Furthermore, hypoxia induced c-Jun-PEA3 complex formation, and U0126 (an ERK inhibitor) or curcumin (an AP­1 inhibitor) downregulated hypoxia-induced Pref-1 expression.
Conclusions
These results implied that ERK, PEA3, and AP­1 participate in hypoxia­induced Pref­1 expression in human lung fibroblasts.