bluuebunny/crossref_metadata_2025 huggingface dataset:
Understandings steps and challenges to take-home naloxone and buprenorphine/naloxone implementation in Québec emergency rooms: SuboxED project
Authors: Talbot Annie , Khemiri Rania , Londei-Leduc Luc , Robin Christine , Marcotte Suzanne , Therrien Guenièvre , Goulet Geneviève , Beaudet-Hillman Geneviève , Ouellette Christine , Brissette Suzanne , Sako Aïssata , Martin Marcel , Lauzon Pierre
Published: May 2020

Background Deaths attributable to drug abuse are on the rise across Canada. It is estimated that there were more than 13,900 opioid-related deaths from January 2016 to June 2019 in the country. Emergency departments (EDs) are often on the frontline of care provided to people at risk of opioid overdose within Québec’s healthcare system. A variety of programs to implement take-home naloxone distribution and/or the provision of opioid agonist treatment for ED patients who are at risk for overdose have been created in the United States and in Europe. However, few EDs in Canada have developed protocols for the provision of take-home naloxone and/or opioid agonist treatment by ED doctors. Methods A clinical algorithm for take home naloxone (THN) and prescription of buprenorphine/naloxone (B/N) was implemented in three EDs of Québec, Canada. This first phase of the SuboxED project required selecting clinical experts, describing the patient population, and creating partnerships with pharmacists and opioid agonist treatment clinics. Results The clinical experts developed tools based on literature reviews and national and international guidelines. They also created educational tools and trained over 328 ED clinical staff. In addition, SuboxED ensured that a supply of take-home naloxone and B/n was available in the three ED sites for the study. Conclusion Implementing the proposed clinical algorithm for THN and prescription of B/N was challenging: drug supply and ED staff’s buy-in were among the most notable difficulties of SuboxED. Planning training sessions at three different institutions, each with its own governance structure and clinical culture, local realities and harm reduction priorities was complicated. Engaging already overworked ED teams consistently working in a gridlocked environments, revealed in itself to be a difficult endeavour. In the next phase of SuboxED, we will focus on data collection and analysis to evaluate both the implementation of the protocol through a retrospective review of electronic health records and satisfaction surveys of patients and healthcare professionals.
Monitoring Physical Activity and Sleep Quality in Children with Blindness and Deafness: A Cross-sectional Study
Authors: Jalal Reema M Al , Ibrahim Alaa I. , Abualait Turki S.
Published: May 2020

Background

Child development has critical links to his ability to see and hear. When these senses are impaired, everything is impacted. The aim of this study was to investigate the effect of visual and hearing impairments on physical activity and sleep quality in a comparison with the normal sighted-hearing children.
Methods

This cross-sectional study included 60 Saudi children (20 blind, 20 sensorineural deaf, and 20 sighted-hearing) aged 10 to 15 years old. The physical activity levels and sleep quality were assessed using a waist-mounted ActiGraph accelerometer.
Results

Children with sensorineural deafness were significantly more active (in step rate and activity rate) than the sighted-hearing group (p = 0.05 and 0.003, respectively). Sighted-hearing children and children with blindness had significantly more sedentary time than children with sensorineural deafness (p = 0.004 and 0.03, respectively). Sleep efficiency was significantly higher in children with sensorineural deafness than sighted-hearing children (p = 0.02). No significant difference was recorded in any of the sleep parameters when children with blindness were compared to the sighted-hearing or children with sensorineural deafness (p > 0.05).
Conclusions

The ActiGraph results revealed that children with sensorineural deafness were significantly more active and with higher sleep efficiency than sighted-hearing children. Children with blindness spent more time in sedentary activities and less time in moderate activities than children with sensorineural deafness. There was no significant difference in sleep efficiency when comparing sensorineural deaf and blind children.
Clinical Characteristics and Predictors of the Recurrence of Organising Pneumonia Associated with Rheumatoid Arthritis
Authors: Kamei Ryosuke , YAMASHITA HIROYUKI , Takahashi Yuko , Kaneko Hiroshi
Published: May 2020

Background: Organizing pneumonia (OP) accounts for ~10% of the interstitial lung diseases in patients diagnosed with rheumatoid arthritis (RA). There are only a few published studies that have described RA-associated OP (RA–OP), each with comparatively few study participants. Furthermore, despite the high frequency of secondary flareups, no studies to date have identified factors that predict RA–OP recurrence. This study aimed to clarify the clinical characteristics of RA–OP, to determine the relationship between OP and RA exacerbations, and to identify predictors of RA–OP disease recurrence.Methods: The data of 33 patients with RA–OP admitted to our hospital between 2006 and 2016 were retrospectively analysed.Results: RA onset preceded OP in 82% of patients; OP preceded or co-occurred with RA in 9% each. The median [Q1, Q3] age at first OP onset was 64.0 [55.0, 68.0] years and 5.5 [1.0, 19.3] years after RA onset. At OP onset, 42% of events exhibited unilateral shadows and 76% had normal KL-6; RA disease control remained good in 52% and was exacerbate d in only 18%. Ten (30%) patients experienced OP recurrence with an interval of 13.0 [7.5, 22.5] months between events, with a rate of first recurrence of 127 per 1,000 person-years. Compared with 14 non-recurrent cases, 10 recurrent cases showed lower age at first OP (59.5 years vs. 67.1 years; p = 0.043) and shorter period from RA to first OP (6.4 vs. 14.2 years; p = 0.047) and included more OP-preceding patients (30% vs. 0%; p = 0.029) and more ever-smokers (80% vs. 36%; p = 0.032). OP-preceding patients showed shorter median recurrence-free survival time (15 vs. 136 months; p = 0.009) and higher recurrence risk (hazard ratio, 5.5; p = 0.021). Conclusions: RA–OP showed a high recurrence rate but no association with RA exacerbation. Four predictors of RA–OP recurrence were identified.
Kinetic analysis of the growth rate of sporadic and hereditary medullary thyroid carcinoma: Comparing the postoperative calcitonin-doubling rate with hypothetical the preoperative tumor volume-doubling rate
Authors: Kihara Minoru , Miyauchi Akira , Masuoka Hiroo , Higashiyama Takuya , Ito Yasuhiro , Miya Akihiro
Published: May 2020

Background Our previous kinetic analyses of changes in the tumor volume (TV) of papillary thyroid microcarcinomas during active surveillance revealed that the tumors' growth varied over time from rather rapid growth to shrinkage and that the hypothetical TV-doubling rates (DRs) before the patients' presentation were much larger than their observed TV-DRs, indicating that rapid growth phases preceded their presentation. Whether this phenomenon also occurs in medullary thyroid carcinoma (MTC) was unknown. Methods We retrospectively analyzed the cases of 46 MTC patients (18 hereditary, 28 sporadic; 9–80 years old at surgery, median 53.5 years; 19 males and 27 females) with elevated postoperative calcitonin (Ct) suggesting persistent disease. We calculated each patient's Ct-DR and his/her hypothetical TV-DR, using the tumor size and age at surgery. Results Ct-DRs (/year) after surgery were >0.5, 0.1–0.5, −0.1–0.1, and ≤0.1 in 9, 21, 12, and 4 patients, respectively (median 0.17). The hypothetical TV-DRs (/year) before surgery were >1, 0.5–1.0, 0.1–0.5 and <0.1 in 11, 21, 14, and 0 patients, respectively (median 0.60). The hypothetical TV-DR was higher than the observed Ct-DR in 41 of the 46 MTC patients and all 18 patients with hereditary MTC, suggesting that a rapid growth phase preceded surgery in these patients. Conclusions In this series of MTC patients, the pre-surgery calculated hypothetical TV-DRs were significantly higher than the Ct-DRs observed post-surgery, suggesting that there were rapid growth periods before surgery in the vast majority of these MTC patients, especially those with hereditary MTC.
Humanized Bispecific Antibody (mPEG×HER2) Rapidly Confers PEGylated nanoaparticles Tumor Specificity for Multimodality Imaging in Breast Cancer
Authors: Cheng Yi-An , Wu Tung-Ho , Wang Yun-Ming , Cheng Tian-Lu , Chen I-Ju , Lu Yun-Chi , Chuang Kuo-Hsiang , Wang Chih-Kuang , Chen Chiao-Yun , Lin Rui-An , Chen Huei-Jen , Liao Tzu-Yi , Liu En-Shuo , Chen Fang-Ming
Published: May 2020

Background: Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG×HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity. Result: We used a one-step formulation to rapidly modify the nanoprobes with mPEG×HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The αHER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2+) but not MCF7/neo1 cells (HER2-). The αHER2/Lipo-DiR and αHER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2+). In in vivo imaging, αHER2/Lipo-DiR and αHER2/SPIO increased the specific targeting and enhanced mPEG-nanoprobe accumulation 161% and 187%, respectively, in HER2-overexpressing tumors. Conclusion: mPEG×HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.
Optical properties in the visible range of two different India ink used as biological phantoms
Authors: Shahin Ali , Bachir Wesam , El-Daher Moustafa Sayem
Published: May 2020

The optical characteristics of two different brands of India ink, Parker Quink and Pelikan, as an absorber used in preparation a tissue-simulating phantom, have been investigated at visible wavelength range. For this purpose, a single integrating sphere system and a spectrophotometric transmission spectroscopy have been used to estimate the radiometric characteristics. Then, inverse adding-doubling algorithm was implemented to retrieve the optical coefficients of pure ink samples. Parker ink's absorption behavior turned out to incompatible with Pelikan over the present wavelength range. Furthermore, scattering property of both two brands has been exhibited and the albedo was calculated. Parker albedo showed a decremental behavior with wavelength and varied between 0.381 and 0.13. A structural profile of albedo was found for Pelikan, which varied between 0.366 and 0.03. This discrepancy might be explained by the variety of two brands composition besides experimental errors. Furthermore, Parker ink absorption variation turned out to be in correspondence to several tissues' absorption feature over broad wavelength ranges. Finally, Parker ink could be regarded as a better candidate to mimic absorption property for several tissues.
Characteristics of Lawsuits against Physicians Charged with Opioid-Related Crimes in the United States, 1995-2019
Authors: Berman Julia B , Li Guohua
Published: May 2020

Background: Pharmaceutical companies and drug distributors are intensely scrutinized in numerous lawsuits for their role in instigating the opioid epidemic. Many individual physicians have also been held accountable for activities related to prescribing opioid medications. The purpose of this study was to examine the epidemiologic patterns of lawsuits against physicians charged with opioid-related crimes in the United States. Methods : We searched the Nexis Uni ® database for newspaper reports on physicians who had been arrested, indicted or criminally charged for illegally prescribing opioids between January 1995 and December 2019. Data collected from the newspaper reports include defendant’s age, sex, clinical specialty, type of crime and legal consequences. Results : The annual number of lawsuits against physicians charged with opioid-related crimes reported by US newspapers increased from 0 in 1995 to 43 in 2019. Of the 384 physician defendants in these lawsuits, 90.4% were male, 28.0% were 65 years and older (mean=59.5 ± 15.8 years), and 23.4% were charged in Florida. Of the 373 physician defendants with known clinical specialty, 243 (65.1%) practiced in internal medicine, family medicine, or pain management. Of the 248 lawsuits with known outcomes, 244 (98.4%) of the defendants were convicted of criminal charges and 4 were acquitted. Drug trafficking was the most commonly convicted crime (accounting for 54.2% of all convicted crimes), followed by fraud (19.1%), money laundering (11.0%) and manslaughter (5.6%). Of the convicted physicians with known sentences, 89.5% were sentenced to jail with an average jail time of 127.3 ± 120.3 months. Conclusions : An increasing number of physicians from a wide variety of clinical specialties is prosecuted for opioid-related crimes with high conviction rates and severe penalties. The most common crime charged is drug trafficking, followed by fraud, money laundering, and manslaughter. Keywords: Drug overdose, Drug trafficking, Opioid Epidemic, Medical fraud, Prescription opioids
Reversible cerebral vasoconstriction syndrome: the importance of follow-up imaging within 2 weeks
Authors: Fukaguchi Kiyomitsu , Goto Tadahiro , Fukui Hiroyuki , Sekine Ichiro , Yamagami Hiroshi
Published: May 2020

Background: In patients with thunderclap headache, reversible cerebral vasoconstriction syndrome (RCVS) should be considered as a differential diagnosis. However, RCVS diagnosis in the emergency department (ED) remains challenging. This study described the clinical features of RCVS, determined the factors related to RCVS diagnosis, and suggested treatment strategies for its management. Methods: We retrospectively identified eight patients diagnosed with RCVS and reviewed their medical records. From January 2010 to March 2019, eight patients with RCVS (ages 18-69 years, 5 females) were identified. Results: The median duration from the ED visit to RCVS diagnosis was 6 days (range, 1-11 days). Of the eight patients, seven were middle-aged, six had apparent triggers, six had subarachnoid haemorrhage (SAH), five had high systolic blood pressure, and none had any specific abnormality observed upon physical examination. At the ED visit, RCVS was diagnosed in only one patient with a history of RCVS. In other patients, SAH was diagnosed in two patients, and primary headache was diagnosed in four patients with negative computed tomography (CT) findings. Based on the follow-up imaging, seven of eight patients with convexal SAH were diagnosed as having RCVS (as the cause of SAH) using angiography (e.g., magnetic resonance angiography). Conclusions: RCVS with negative CT findings at the ED visit was likely to be misdiagnosed as primary headache. In patients with thunderclap headache and negative CT findings, physicians should consider RCVS as a differential diagnosis, inform patients of the risk of RCVS and the likelihood of a negative image evaluation early in the course of the disease, and carry out follow-up imaging within 2-weeks of the visit.
Cardiovascular Outcomes in Patients with Initial Diagnosis of Obstructive Coronary Artery Disease and LDL-C below 1.8 mmol/L
Authors: Zhang Yue , Zhao Xueqiao , Li Hongwei , Ding Xiaosong , Li Dandan , Chen Hui , Li Weiping
Published: May 2020

Background To investigate individuals at high risk for atherosclerotic cardiovascular disease (ASCVD), but, without previous events and with low-density lipoprotein cholesterol(LDL-C)<1.8 mmol/L should be treated with statin. Methods: We studied 1330 patients with LDL-C <1.8 mmol/L at the initial diagnosis of obstructive coronary atherosclerotic disease (OCAD) by angiography. Of 1330, 782 had not received prior statin therapy and 548 were treated with statin. Incidence of subsequent major adverse cardiac and cerebral event (MACCE) during a median of 25-month follow-up were identified and compared between patients with LDL-C <1.8 mmol/L without any prior statin [prior statin(-)] and those with LDL-C <1.8mmol/L achieved by prior statin therapy [prior statin(+)].Results ACS occurred in 93.4% of individuals with LDL-C <1.8 mmol/L as an initial diagnosis of OCAD. Prior statin(+), comparing to prior statin(-) who displayed similar ASCVD risk burden including 71.6% with hypertension, 39.1% with diabetes and 76.1% with ≥3 risk factors, had significantly lower incidence of acute myocardial infarction(AMI) (10.4% vs. 28.8%, P<0.001), higher left ventricular ejection fraction(LVEF)(0.67±0.07 vs. 0.64±0.09, P <0.001), lower incidences of subsequent MACCE (4.7% vs. 10.4%, P =0.001), total mortality (2.4% vs. 6.8%, P =0.001) and cardiovascular(CV) death (1.5% vs. 4.3%, P =0.006) during follow-up. After multivariable adjustment, no prior statin therapy was significantly and independently associated with subsequent CV death, particularly in the subgroups of age≥65 years and hypertension. Conclusions Prior statin therapy to achieve LDL-C <1.8 mmol/L comparing to LDL-C <1.8 mmol/L without statin independently predicted lower risk of subsequent CV death and better prognosis.
Activated Hepatic Stellate Cells Induce Infiltration and Formation of CD163+ Macrophages via CCL2/CCR2 Pathway
Authors: Xi Sujuan , Zheng Xiaoyan , Jiang Yuming , Wu Yuankai , Gong Jiao , Jie Yusheng , Li Xiangyong , Cao Jing , Sha Liuping , Zhang Min , Chong Yutian
Published: May 2020

Background: Growing evidence indicates that activated hepatic stellate cells (aHSCs) play unexpected roles in regulating immune cells’ function during liver fibrosis. Macrophages feature with inducible plasticity according to the circumstances while patrol for potential pathogens. However, studies seldom investigate whether and how the aHSCs regulate the phenotype and function of macrophages during liver fibrosis. Methods: 96 patients with different stages of liver fibrosis were involved in our study. Metavir score system was used to evaluate the degree of fibrosis. The expression of hepatic CCL2 and CD163 were detected by immunohistochemistry, and the relationship among CD163, CCL2, and fibrosis scores were explored. We co-cultured the aHSCs and THP-1-derived M0-type macrophages (M0MФ) to observe whether aHSCs modulate the expression of CD163 on macrophages in vitro. Furthermore, we treated the M0MФ with aHSCs’ supernatant and investigated the production of CCL2 in aHSCs by ELISA and immunofluorescence assay. To explore whether CCL2/CCR2 axis plays a crucial role in macrophage phenotypic changes during liver fibrosis, we used recombinant CCL2 and its specific receptor antagonist. Moreover, we employed LX2 system to confirm our results. Results: We found that hepatic M2 macrophages (CD163+) infiltration increased in different stages of liver fibrosis (F0-1: 34.95±18.12; F2-3: 77.57±32.48; F4: 99.62±40.84, F0-1 vs. F2-3, P<0.001; F2-3 vs. F4, P=0.074). After in vitro co-cultured with aHSCs, the macrophages expressed higher levels of CD163 (29.5±6.1% vs. 2.7±1.1%) as well as CD206 (28.0±4.2% vs. 2.4±1.2%) compared with the control. Then we found aHSC supernatant up-regulated the expression of CD163 (26.1±2.8%) and CD206 (25.8±3.8%) on macrophages independently. We noted aHSCs’ supernatant contained a high level of CCL2, which increased dramatically while TGF-β stimulation. Meanwhile, CCL2 staining score increased with the progress of fibrosis ( N: 23.26±13.85; F1: 4 8.56±19.18; F2: 58.25±16.24; F3: 81.32±18.48; F4: 110.93±24.75). Intriguingly, CCL2 significantly up-regulated the expression of CD163 (27.6±7.0%) and CD206 (26.5±5.1%) on macrophages besides inducing their aggregation. Results were confirmed with LX2 co-culture system. Conclusions: (1) The expression of M2 macrophage marker CD163 increased significantly during the progress of liver fibrosis and associated with fibrosis severity. (2) AHSCs can recruit macrophages and induce their M2 phenotypic transformation through CCL2/CCR2 pathway.
Identification of an EMT-related lncRNA signature in glioma
Authors: Tao Chuming , Hu Qing , Luo Haitao , Wang Peng , Tu Zewei , Guo Hua , Huang Kai , Zhu Xingen
Published: May 2020

Background Epithelial-mesenchymal transition (EMT) has been implicated in the invasion and progression of gliomas, the present study investigated EMT-related long noncoding (lnc)RNAs in gliomas.Methods Candidate lncRNAs screened from a glioma dataset in The Cancer Genome Atlas were used to construct EMT-related lncRNA coexpression networks in order to identify EMT-related lncRNAs; these were validated using the Chinese Glioma Genome Atlas (CGGA). Gene set enrichment analysis and principal component analysis (PCA) were used to annotate lncRNA functions. We established an EMT-related lncRNA signature composed of 9 lncRNAs (HAR1A, LINC00641, LINC00900, MIR210HG, MIR22HG, PVT1, SLC25A21-AS1, SNAI3-AS1, and SNHG18) that could distinguish between low- and high-risk glioma patients. The functions of the identified lncRNAs were evaluated by constructing a competing endogenous RNA network.Results The low-risk group had longer overall survival (OS) than the high-risk group (P<0.0001). High-risk patients also had no deletion on chromosome arms 1p and/or 19q, expressed wild-type isocitrate dehydrogenase, and had higher World Health Organization (WHO) tumor grade. The signature was an independent factor significantly associated with OS (P=0.041, hazard ratio=1.806). These findings were validated in the CGGA dataset. PCA also revealed differences in EMT status between low- and high-risk patients. Competing endogenous RNA network showed that complex lncRNA–microRNA–mRNA interactions potentially contributing to EMT progression in glioma. Conclusion Our results demonstrate that the EMT-related 9-lncRNA signature has prognostic value for glioma patients.
Hemodynamics During the 10-Minute NASA Lean Test: Evidence of Circulatory Decompensation in a Subset of ME/CFS Patients
Authors: Lee Jihyun , Vernon Suzanne D , Jeys Patricia , Ali Weam , Campos Andrea , Unutmaz Derya , Yellman Brayden , Bateman Lucinda
Published: May 2020

Background Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was t o understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT. Methods A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (<4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (>10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 minutes while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups. Results At least 5 minutes of the 10-minute NLT were required to detect hemodynamic changes. The <4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to >10 ME/CFS and HCs. The <4 ME/CFS group experienced significantly more OI symptoms compared to >10 ME/CFS and HCs. The circulatory decompensation observed in the <4 ME/CFS group was not related to age or medication use. Conclusions Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for <4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The >10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.
Definitions of segmental instability in the degenerative lumbar spine and validation of these definitions: a systematic review protocol article according to PRISMA-P 2015 statement
Authors: Elmose Signe Forbech , Andersen Gustav Østerheden , Carreon Leah Yacat , Sigmundsson Freyr Gauti , Andersen Mikkel Østerheden
Published: May 2020

Background The concept of segmental lumbar spine instability is controversial with varying definitions. However, suspicion of instability is used as an indication for vertebral fusion surgery in patients with lumbar degenerative spondylolisthesis and spinal stenosis. The objectives of this systematic review are to describe, the definitions of segmental instability in the degenerative lumbar spine, in studies of patients with lumbar spinal stenosis and/or lumbar degenerative spondylolisthesis, involving diagnostic imaging. And to describe which of the measurable radiological variables used to define instability have been validated against dynamic flexion-extension radiographs. Method Systematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Systematic literature search will be conducted in MEDLINE and EMBASE databases, supplemented by search in Cochrane Library. International Clinical Trials Registry Platform Search Portal and ClinicalTrials.gov will be searched for ongoing or recently completed trials. PROSPERO (International Prospective Register of Systematic Reviews) will be searched before initiating this review. In addition, a gray literature search will be conducted. Studies eligible for inclusion are clinical and biomechanical studies on adult patients with degenerative spondylolisthesis and spinal stenosis and surgical treatment hereof, studies involving diagnostic imaging. We will include studies giving a definition or describing patho-anatomical findings of segmental instability or any synonym or antonym hereof. Two reviewers will independently screen articles, involving a third reviewer as referee. Screening process and data extraction conducted using Covidence software. Data synthesis presented in results checklist and systematic narrative synthesis. Data synthesis on secondary objective by contingency table. Discussion With this systematic review we want to contribute to evidence based treatment planning of lumbar degenerative spondylolisthesis with spinal stenosis. We also aim to present our result in a comprehensive manner, to encourage consensus regarding the definition of segmental instability. Registration This protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO) on 29. April 2020, submission ID: 182827
Improving the control ability of pulmonary tuberculosis with an internet based eDOTS system in the communities of Kashgar and Urumqi, Xinjiang of China
Authors: Guo Gang , Sun Li , Wushouer Qimanguli , Jia Bin , Yusufu Muladier , Wen Shu , Abudureyimu Tuerhong , Peng Xiaowang , Liu Zhenjiang , Mamuti Xirizat , Chen Yanggui , Zhang Jian , Yang Yuling , Huangfu Liusheng , Li Jun , Zhang Wenbao
Published: May 2020

Background: Although the direct observed treatment strategy (DOTS) has been used for the control of pulmonary tuberculosis (PTB) in Xinjiang Uygur Autonomous Region for more than 30 years, the disease is still highly endemic in the region. To increase ability of PTB treatment and control efficacy, we developed a new eDOTS system for reminding, monitoring and educating PTB patients for regularly taking antibiotics.Methods: A total 167 new cases with active PTB from Kashgar villages and Urumqi City in Xinjiang were involved in the study. Among them, 81 patients were from villages with 43 patients using eDOTS system and 38 patients with traditional DOTS as control. Eighty six patients were from township with 50 patients using eDOTS and 36 patients using DOTS. Findings: PTB patients from villages in Kashgar treated with DOTS showed low compliance of taking antibiotics, only 27.9% the patients took medicine consistently once the network service for eDOTS system was removed. However, with the help of village and hospital doctors through the eDOTS system, the medical compliance were increased to 70-85%. The treatment compliance with eDOTS of patients from township (100%) was significantly higher than that of those patients from the rural villages (49%) in the first 6 weeks ( Χ 2 =33.3, P <0.01). DR X-ray Scores of PTB lesions showed that the patients using eDOTS either from the villages or from township significantly decreased their lesion score points compared to these scores from those patients using DOTS by 1.81 points，95% CI (0.72-2.90) and 1.05 points，95% CI (0.15-1.95) after 25 weeks of treatment, respectively. In the township, those 50 patients were looked after by one community doctor with eDOTS. Conclusion: eDOTS is an effective means of treating PTB patients in terms of reducing doctor’s work and increasing the compliance of taking antibiotics regularly during the treatment course. One doctor can easily look after 50 or more PTB patients through the eDOTS system. The constantly education program online through the system for the patients especially in villages plays an important role in encouraging TB patients taking antibiotics for a long period.
Modelling the Paucity of COVID-19 Pandemic Spread Incidence across the India Nation
Authors: Rodriguez-Morales Alfonso J. , Singh Ram Kumar , Singh S. S. , Pandey A. K. , Kumar Vinod , Jha Ramadhar , Bala Raj , Sah Ranjit , Sharma Pardeep , Mandal Vinay Prasad , Kalita Himangshu , Nandan Rajiv , Singh Susheel Kumar , Rabaan Ali A. , Rani Meenu , Kumar Pavan , Kumar Manoj
Published: May 2020

Background: The highly contagious Co rona vi rus d isease (COVID-19) pandemic affected nearly all nations across the world. It was emerged as most swiftly affected disease across the world and more than 2934 lakhs population suffered in four months of the time period as on date April 26, 2020. Its first epicenter was at Wuhan city of China during the month of December 2019. Currently, the most affected people and new epicenter of Coronavirus is at the United States of America (USA). Various nation’s administration including the India government called for the regional and local lockdown. We predicted the confirmed COVID-19 cases for next May-2020 month, map the magnitude of COVID-19 disease for Indian states and model the paucity of COVID-19 disease with statistical confirmatory data analysis model for declining rate for the cases represented for the Indian proportion of population. Method: The ARIMA model used to predict for next short-term cases, based moving average of past confirmed cases. The restriction of COVID-19 pandemic disease analyzed with predicted cases for month May 2020 data at 95 percent confidence is more than 2.5 lakh cases. Results: The confirmatory data analysis model for the time estimation for the paucity of cases it takes in between six to eighteen months of time frame. The Confirmatory model which considers recovery rate, social, economic and government policy. To complete recovery from the COVID-19 cases it takes on an average more than next ten months. Conclusion: The disease impacts also depend upon administrative and local people support for self-quarantine and other measures. The India nation Gross Domestic Product (GDP) based on more than 17% of its agriculture production, due to longer affect of the disease and extended lockdown period it will be severely affected. However, all the economic activities with full of its intensity takes-up after complete paucity of COVID-19 disease spread. Keywords: SARS-CoV-2; Lockdown; GDP; Nobel-Corona; Confirmatory data model
KLF5-mediated Eppk1 expression promotes cell proliferation in cervical cancer via the p38 signaling pathway
Authors: Pan Zhe , Liu Xiao , Chang Quan , Zhang Jin-jin , Hua Na , Li Guo-Hua , Ma Dong
Published: May 2020

Background: Epiplakin1 (Eppk1) is part of the EGF signal and is involved in cytoskeleton reorganization and cell proliferation. However, the role of Eppk1 in cervical cancer remains unknown. Objective: To determine the role of EPPK1 on cell proliferation in cervical cancer. Methods: The expression of Eppk1 and KLF5 as well as their correlation were assessed by RNA-seq, qRT-PCR, TCGA database and immunofluorescence staining. In CC cell lines, adenovirus-mediated overexpression or knockdown of KLF5 and Eppk1 as well as corresponding assessment of cell proliferation and signaling were determined by western blot and CCK8 experiments. Assays of lucifase reporter gene and CHIP were used to investigate mechanism between KLF5 and Eppk1 . Results: Eppk1 expression was markedly in CC tissues and cell lines companied by KLF5 upregulation. The results of immunofluorescence staining further showed that the increased expression of Eppk1 and KLF5 correlated with progression of cervical tumorigenesis. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanical studies showed that KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments showed that KLF5 promoted cell proliferation in Hela by upregulating Eppk1 expression. Moreover, KLF5-mediated the activation of EGFR and p38 signaling significantly decreased after Eppk1 knockdown companied with reduction of proliferating activity, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation in CC. Finally, the expression of Eppk1 positively correlated with tumor size. Conclusions: Eppk1 may be an effective therapeutic target on affecting EGFR-associated p38 signaling pathway and cell proliferation in cervical cancer.
The Inhibition of Autophagy Flux Mediated by Neferine Promoted the Apoptosis of HNSCC through the Accumulation of p62/SQSTM1
Authors: Zhu Fengshuo , Li Xiaoguang , Tang Xiao , Jiang Junjian , Han Yu , Li Yinuo , Liu Zhonglong , He Yue
Published: May 2020

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Patients usually have very poor prognosis because of metastasis and chemoresistance. There is an imperative need to explore more effective chemotherapeutic agents. Neferine, a bisbenzylisoquinoline alkaloid isolated from the seed embryo of Lotus, exerts antitumor effects via regulating apoptosis and autophagy pathways, which becomes a potential therapeutic option for HNSCC. Methods: Cell viability and proliferation was determined by the CCK8 and colony formation assay. Cell cycle and apoptosis analysis were assessed by flow cytometry with Annexin V-FITC/PI staining. Intracellular ROS levels were determined by the DCFH-DA fluorescence. Autophagy flux was detected by transmission electron microscopy, transfected GFP-RFP-LC3 fluorescence and western blot for related markers in the presence or absence of neferine and chloroquine. Results: Neferine inhibited the growth and induce the apoptosis of HNSCC cells both in vitro and vivo. Further analysis revealed that neferine activated ASK1/JNK pathway by increasing reactive oxygen species, then induced apoptosis of and regulated canonical autophagy in HNSCC cells. The study also revealed the novel pro-apoptosis mechanism through the activation of Caspase8 mediated by p62 due to the inhibition of autophagy flux. Conclusions: These findings explore the anti-cancer effect of neferine, providing new insights into the crosstalk between apoptosis and autophagy mediated by p62 in HNSCC. The inhibition of autophagy flux by neferine might be a potential adjuvant therapy to HNSCC.
Spike protein amino acid variants increased miRNA binding and hence reduced virulence of SARS-CoV-2 in Jordan, Middle East
Authors: Haddad Hazem , Foudeh Ramzi , Al-Zyoud Walid
Published: May 2020

Initial epidemiological studies inform the central COVID-19 disease prophet. Some papers have been studying miRNA and viral RNA interaction target predictions over the past few years. In this work, via the miRDB database, we determined the target scores of predicted miRNA to bind with the ss-RNA of SARS-CoV-2 in general and spike gene in specific. Our predicted miRNA targets of the ss-RNA of SARS-CoV-2 might destabilize and hence inhibit the ss-RNA translation of SARS-CoV-2 and prevent viral replication that has been established by more than 80% of asymptomatic infected cases in Jordan due to host miRNA interactions. In respiratory epithelial cells, the high scoring miRNAs prediction covers the RNA from 5' to 3' that explain successful antiviral defenses against ss-RNA of SARS-CoV-2 and lead to new nucleotide deletion mechanisms. The exciting finding here that the substitution 1841A>G at the viral genomic RNA level or the D614G at spike protein level showed a change in the predicted miRNA sequence and an increase in the target score (from 91 to 92) (hsa-miR-4793-5p to hsa-miR-3620-3p).
Fast and low-cost detection of SARS-CoV-2 peptides by tandem mass spectrometry in clinical samples
Authors: Cardozo Karina Helena Morais , Lebkuchen Adriana , Okai Guilherme Goncalves , Schuch Rodrigo Andrade , Viana Luciana Godoy , Olive Aline Nogueira , Lazari Carolina dos Santos , Fraga Ana Maria , Granato Celso , Carvalho Valdemir Melechco
Published: May 2020

The current outbreak of severe acute respiratory syndrome associated with coronavirus 2 (SARS-CoV-2) is pressing public health systems around the world, and large population testing is a key step to control this pandemic disease. Real-time reverse-transcription PCR (real-time RT-PCR) is the gold standard test for virus detection but the soaring demand for this test resulted in shortage of reagents and instruments, severely limiting its applicability to large-scale screening. To be used either as an alternative, or as a complement, to real-time RT-PCR testing, we developed a high-throughput targeted proteomics assay to detect SARS-CoV-2 proteins directly from clinical respiratory tract samples. Sample preparation was fully automated by using a modified magnetic particle-based proteomics approach implemented on a robotic liquid handler, enabling a fast processing of samples. The use of turbulent flow chromatography included four times multiplexed on-line sample cleanup and UPLC separation. MS/MS detection of three peptides from SARS-CoV-2 nucleoprotein and a 15N-labeled internal global standard was achieved within 2.5 min, enabling the analysis of more than 500 samples per day. The method was validated using 562 specimens previously analyzed by real-time RT-PCR and was able to detect over 83% of positive cases. No interference was found with samples from common respiratory viruses, including other coronaviruses (NL63, OC43, HKU1, and 229E). The strategy here presented has high sample stability and low cost and should be considered as an option to large population testing.
A practical nomogram from the SEER database to predict the prognosis of hepatocellular carcinoma patients with lymph node metastasis
Authors: Zhang Kai , Tao Changcheng , Wu Jianxiong , Rong Weiqi
Published: May 2020

Background: The presence of lymph node metastases is related to poor survival outcomes in hepatocellular carcinoma patients and because of the reported low probability of lymph node metastasis, research into the prognoses of such patients is difficult to conduct. In this study, we aimed to develop a nomogram model to predict the prognosis of HCC patients with lymph node metastasis and provided a reasonable basis for the choice of follow-up treatment.Methods: HCC patients diagnosed with LN metastasis from 2010 to 2015 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate Cox regression and lasso regression were used to screen prognostic factors. Cox multiple-factor analysis was employed to investigate the independent prognostic factors for survival. The concordance index (C-index) and calibration curve were used to evaluate the predictive performance of our model. The clinical benefit was assessed via decision curve analysis (DCA). The survival was analyzed using Kaplan-Meier method and the differences among survival curves were compared by the log-rank test.Results: Patients were randomized into the training group (944 patients) and the validation group (402 patients) in a 70:30 ratio. Grade, T stage, surgery to the liver, chemotherapy, radiation recode, AFP, fibrosis score, tumor size group, M stage were selected as independent prognostic factors, and we developed nomograms using these variables. The c-indices of the training and validation groups were 0.70 and 0.73, respectively. The calibration curves for probability of survival showed good agreement. The DCA indicated that the nomogram had positive net benefits. Patients were divided into two risk groups according to our model, survival curves were drawn, and the log-rank test was performed, the p-value of which was <0.001.Conclusions: The nomogram can accurately predict the prognosis of HCC patients with lymph nodes metastasis and provide a reasonable basis for treatment.
Surgical Management of Bladder Cancer During First Month of COVID-19 Outbreak: Lessons Learned Across Italy
Authors: Maccagnano Carmen , Rocchini Lorenzo , Montanari Emanuele , Conti Giario Natale , Contieri Roberto , Bryan Kadi-Anna , Hurle Rodolfo
Published: May 2020

Objectives: Real-life overview of bladder cancer (BC) surgical management in Italy during the first month of COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to confront performance of Academic Centers (AC) vs Non Academic Centers (NAC) as well as non-COVID Centers (nCC) and COVID Centers (CC). Patients and methods: During April 2020, an e-mail survey was sent to 32 Sections of Urology across Italy. It contained 14 multiple-choice questions focused on activities during March 2019 and March 2020. Statistical analysis was performed using IBM SPSS Statistics (v26) software. Results28 centers answered to survey. AC and NAC showed statistically significant differences (chi-square test p<0.05) about number of physicians assigned to Covid wards (p=0.001), Trans-Urethral Resection of Bladder Tumour (TURBT) (p=0.046) and cystectomies (p=0.037) performed in March 2020 (p=0.037). In 2020, AC performed more surgical procedures compared to NAC. In 2019, AC had more procedures per Operating Block (OB) (p=0.015) and greater number of emergent Trans-Urethral Resections (TUR) (p=0.014), while NAC had more TURBTs. CC had more patients (pts) both evaluated for gross hematuria (p=0.017) and requiring haemostatic Trans-Urethral Resection (hTUR) in 2019. In 2020 nCC had more surgeries per OB (p=0.001), TURBTs (p=0.030) and cystectomies (p=0.034) than CC. ConclusionThe COVID-19 pandemic represents an important challenge for cancer centers, in the context of an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.
Evaluating extremely low plasma ascorbate levels and reduction of plasma ascorbate levels by dialysis in Japanese hemodialysis patients
Authors: Doshida Yuta , Itabashi Mitsuyo , Takei Takashi , Takino Yuka , Sato Ayami , Yatsu Tomofumi , Yumura Wako , Maruyama Naoki , Ishigami Akihito
Published: May 2020

Background: Low plasma ascorbate levels in hemodialysis patients have been reported worldwide; hence, many end-stage kidney disease patients are forced to restrict their diets, especially potassium-rich fruits and vegetables, to prevent hyperkalemia. In this study, we aimed to clarify whether plasma ascorbate levels are low in Japanese dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. In addition, we aimed to clarify whether there are clinical test items that have a causal relationship with plasma ascorbate levels.Methods: Plasma ascorbate levels in 27 chronic kidney disease (CKD) stage G3–G5 patients (mean age 84 years) and pre- and post-dialysis plasma ascorbate levels in 19 CKD stage G5D hemodialysis patients (mean age 79 years) were determined using high-performance liquid chromatography and electrochemical detection.Results: Pre-dialysis plasma ascorbate levels in hemodialysis patients (12.0 ± 1.4 µM) were significantly lower (by 56%) than those in CKD stage G3–G5 patients (27.1 ± 2.7 µM). After dialysis, there was a 40% reduction in plasma ascorbate levels. Moreover, pre-dialysis ascorbate levels correlated significantly with plasma potassium levels.Conclusions: The study results indicate that Japanese hemodialysis patients have lower plasma ascorbate levels than CKD stage G3–G5 patients and that these low plasma ascorbate levels in hemodialysis patients were further reduced by hemodialysis. To avoid the development of scurvy in hemodialysis patients, it is necessary to take sufficient ascorbate from supplements or medicines.
Cox Regression Analysis of 1739 Emergency Trauma Patients
Authors: Shen Jun , Xu Feng , Chen Du
Published: May 2020

BACKGROUND: Trauma is a damage caused by physical harm from external source. It has been one of the major causes of mortality. The purpose of this study was to explore the risk factors related to mortality among emergency trauma patients. METHODS: This was a retrospective study in trauma center of the First Affiliated Hospital of Soochow University. The data were obtained from trauma database with patients registered from November 1, 2016 to November 30, 2019.Shapiro–Wilk test, Mann-Whitney test and Likelihood-ratio Chi squared test were used to assess the survival pattern. Cox regressions were performed to calculate the hazard ratios (HRs) of variables for death. RESULTS: The total 1739 emergency trauma patients, 44 (2.53%) died during the study period and 1695 (97.47%) were survival. Through univariable and multivariable Cox regression analysis, three independent risk factors for emergency death were screened out: pulse (Crude HR: 0.97, 95% Confidence Interval [CI]: 0.96-0.98; Adjuste HR: 1.04, 95% CI: 1.02-1.06), pulse oxygen saturation (Crude HR: 0.96, 95% CI: 0.95-0.97; Adjuste HR: 0.94, 95% CI: 0.91-0.97) and Revised Trauma Score (Crude HR: 0.69, 95% CI: 0.65-0.74; Adjuste HR: 0.79, 95% CI: 0.64-0.97).CONCLUSION: The survival outcome of emergency trauma patients was influenced by many factors. Pulse, pulse oxygen saturation (SpO2 ) and Revised Trauma Score (RTS) were the independent risk factors for mortality. Accurate analysis and judgment of the risk factors can improve cure efficiency and long-term survival rate.