bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL
Authors: Chen Chih-Hao , Cheng Yu-Wen , Chen Ya-Fang , Tang Sung-Chun , Jeng Jiann-Shing
Published: March 2020

Background

Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients.

Methods

Sixty-three CADASIL patients (mean age 58.9±9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up.

Results

Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 Common.EditSubmissionSteps.Transform.EquationText 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH.

Conclusions

In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.
Cross-cultural validation of the Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction scale in the Dutch general population
Authors: Joxhorst Tessa , Vrijsen Joyce , Niebuur Jacobien , Smidt Nynke
Published: March 2020

BACKGROUND: This study aims to translate and validate the Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction (MCLHB-DRR) scale in the Dutch general population.

METHODS: A random sample of Dutch residents aged between 30 and 80 years old were invited to complete an online questionnaire including the translated MCLHB-DRR scale. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted to assess construct validity. Cronbach’s alpha was calculated to assess internal consistency.

RESULTS: 618 participants completed the questionnaire. EFA and Cronbach’s alpha showed that four items were candidate for deletion. CFA confirmed that deleting these items led to an excellent fit (RMSEA = 0.043, CFI = 0.960, TLI = 0.951, χ²/df = 2.130). Cronbach’s alpha ranged from 0.69 to 0.93, indicating good internal consistency.

CONCLUSION: The current study demonstrated that the Dutch MCLHB-DRR scale is a valid scale for assessing health beliefs and attitudes towards dementia risk reduction among Dutch adults aged between 30 and 80 years old.
Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening
Authors: Ge Xin , Zhang Xiaolei , Ma Yanling , Chen Shaohua , Chen Zhaowu , Li Ming
Published: March 2020

BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.
Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
Authors: Bendtsen Katja Maria , Gren Louise , Malmborg Vilhelm Berg , Shukla Pravesh Chandra , Tunér Martin , Essig Yona J , Krais Annette M , Clausen Per Axel , Berthing Trine , Loeschner Katrin , Jacobsen Nicklas Raun , Wolff Henrik , Pagels Joakim , Vogel Ulla B
Published: March 2020

Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O 2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O 2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28 and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m 2 /g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 mg/mg) and acid-extractable metal content (0.9-16 mg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in liver on day 90 correlated with acellular particle-induced ROS.Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights particle size, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
Non–anti-TNF biologic agents not associated with a worsening of lung disease secondary to rheumatoid arthritis.
Authors: Vázquez Natalia Mena , Godoy-Navarrete Francisco Javier , Manrique-Arija Sara , Aguilar-Hurtado Maria Carmen , Romero-Barco Carmen María , Ureña-Garnica Inmaculada , Añón-Oñate Isabel , Pérez-Albaladejo Lorena , Gomez-Cano Carmen , Jimenez-Núñez Francisco Gabriel , Padin-Martín Maria Isabel , Fernández-Nebro Antonio
Published: March 2020

Objectives To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). Patients and methods We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was change in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. Results After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). Conclusions Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non–anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening.
Persistence of Pregabalin Treatment in Taiwan: a Nation-Wide Population-Based Study
Authors: Wang Yen-Feng , Chen Yung-Tai , Tsai Ching-Wen , Yen Yu-Chun , Chen Yi-Chun , Hsia Ben-Chang , Wang Shuu-Jiun
Published: March 2020

Background Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored. Methods This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis. Results Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7±15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14-118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09-1.18), older age (OR 1.01 per year, 95% CI 1.01-1.01), indications other than PNH, especially epilepsy (OR 8.04, 95% CI 7.33-8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI=1.10-1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35-0.47). Conclusions Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was typically below the recommended ranges. Potential causes included off-label prescriptions for pain in acute herpes zoster, rather than PNH, as well as intolerance to the side effects. Keywords pregabalin, pain, persistence
Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction
Authors: Wang Hao Hao , Lu Hao Hao , Zhang Xiao-Meng Xiao-Meng , Goto Ken-ichiro Ken-ichiro , Kobayashi Eiichi Eiichi , Yoshida Yoichi Yoichi , Adachi Akihiko Akihiko , Matsutani Tomoo Tomoo , Iwadate Yasuo Yasuo , Min Seiichiro Seiichiro , Machida Toshio Toshio , Sata Mizuki Mizuki , Yamagishi Kazumasa Kazumasa , Iso Hiroyasu Hiroyasu , Sawada Norie Norie , Tsugane Shoichiro Shoichiro , Kamitsukasa Ikuo Ikuo , Wada Takeshi Takeshi , Aotsuka Akiyo Akiyo , Sugimoto Kazuo Kazuo , Takizawa Hirotaka Hirotaka , Kashiwado Koichi Koichi , Shin Hideo Hideo , Tomiyoshi Go Go , Nakamura Rika Rika , Shinmen Natsuko Natsuko , Kuroda Hideyuki Hideyuki , Xu Anding Anding , Hiwasa Takaki
Published: March 2020

Background and Purpose: Ischemic stroke, such as Transient ischemic attack (TIA) and cerebral infarction (CI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and CI is attempted.Methods: Candidate antigens recognized by IgG autoantibodies in the sera of nineteen TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and CI cohorts (n = 285, 92 and 529). A case-control study nested within the Japan Public Health Center-based Prospective Cohort Study (JPHC) was performed.Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that anti-ALDOA and anti-FH antibody levels were both higher in TIA or CI patients than in HDs ( P < 0.0001). The levels of anti-ALDOA [Odds ratio (OR): 2.46, P = 0.005] and anti-FH (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis, similar results were found in CI. The case-control study showed the levels of anti-ALDOA (OR: 2.50, P < 0.01) and anti-FH (OR: 2.60, P < 0.01) were associated with risk of CI. Spearman’s correlation analysis demonstrated an association between the anti-ALDOA and anti-FH levels and risk factors of ischemic stroke, such as age, smoking habit, coronary heart disease, and hypertension.Conclusions: Anti-ALDOA and anti-FH antibodies can serve as novel potential biomarkers for prediction of TIA and CI.
Functional decline in geriatric rehabilitation ward; is it ascribable to Hospital Acquired Infection? A prospective cohort study.
Authors: Laurent Marie , Oubaya Nadia , David Jean Philippe , Poitrine Florence Canoui , Corsin Lola , Liuu Evelyne , Audureau Etienne , Garin Sylvie Bastuji , Paillaud Elena
Published: March 2020

Background: Some patients may not benefit from their stay in a geriatric rehabilitation unit and paradoxically worsened their functional status. The incidence of functional decline in these units and factors associated with this decline have not been clearly identified. Methods: We used a prospective cohort of consecutive patients aged ≥ 75 years admitted to a geriatric rehabilitation unit in a French university hospital. The main endpoint was functional decline defined by at least an one-point decrease in Activities of Daily Living (ADL) score during the stay. Baseline social and geriatric characteristics were recorded and comorbidities were sought by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). During follow-up, hospital-acquired infection (HAI) was recorded, as was ADL score at discharge. Multivariate logistic regression and mediation analyses were used to identify factors associated with ADL decrease. Results : Among the 252 eligible patients, 165 (median age 85 years [interquartile range (IQR) 81-90] had available ADL scores at baseline (median score 7 [IQR 4-10]) and at discharge (median 9 [6-12]). Median CIRS-G score was 11 [9-13], 24 (14.5%) had a pulmonary HAI; 30 (18.2%) showed functional decline. On multivariable analysis, functional decline was associated with comorbidities (global CIRS-G score, P=0.02, CIRS-G for respiratory disease [CIRS-G-R] ≥2, P=0.03, or psychiatric disease, P=0.02) and albumin level < 35 g/l (p=0.02). Significant association were found between functional decline and CIRS-G for respiratory diseases (CIRS-G-R) (OR 2.82 [95% CI 1.18-6.71], p=0.016), between functional decline and pulmonary HAI (OR 4.09 [1.48-11.34],p=4.09), and between CIRS-G-R and pulmonary HAI (OR 10.9 [5.26-22.5],p=0.0001). Theses associations and the reduced effect of CIRS-G-R on functional decline after adjusting for pulmonary HAI (OR 1.91 [0.71-5.16], p=0.20) suggested partial mediation of pulmonary HAI in the relation between CIRS-G-R and functional decline. Conclusion : Baseline comorbidities were independently associated with functional decline in patients hospitalized in a geriatric rehabilitation unit. Pulmonary HAI may have mediated this association. We need to better identify patients at risk of functional decline before transfer to a rehabilitation unit and to test the implementation of modern and individual programs of rehabilitation outside the hospital for these patients.
Bomb Blast: Imaging Findings, Treatment and Clinical Course of Extremity Traumas
Authors: Tahtabasi Mehmet , Er Sadettin , Karasu Recep , Ucaroglu Erhan Renan
Published: March 2020

Background: To determine the severity and types of blast-related extremity injuries and the presence of accompanying vascular injuries (VI) and amputation, and to identify the predictive factors affecting the treatment management and clinical course.Methods: The study included 101 patients with extremity injuries caused by a bomb explosion. The radiographs and computed tomography angiographies of the patients were evaluated in terms of injury patterns, presence of shrapnel fragments and fractures, and localization (upper or lower extremity) and type (open or closed) of injury. In addition, the presence of soft tissue injuries and VI was recorded. The Gustilo-Anderson classification was used for open fractures. According to their severity, open fractures classified as types 1, 2 and 3A were included in Group 1 and those classified as type 3B and 3C in Group 2.Results: As a result of the explosion, 101 (57.7%) patients had extremity injuries, of which 76 (75.2%) presented with at least one fracture. Of the total of 103 fractures, nine (8.8%) were closed and 94 (91.2%) were open. Thirty-eight (40.4%) of the open fractures were located in the upper extremities, and 56 (59.6%) in the lower extremities and pelvis. Open fractures were most frequently localized in the femur (n=20; 21.2%), followed by the tibia (n=18; 19.1%). The majority of patients with open fractures were in Group 1 (74.2%). The duration of hospital stay was longer in Group 2 (11.7±5.8 vs. 6.8±6.7 days, p <0.0001). Mortality among patients in Group 2 (44.4%) was significantly higher than in Group 1 (6.1%) ( p <0.0001). Similarly, the injury severity score (ISS) was higher in Group 2 (median 20 vs. 9, p<0.0001). Similarly, the rate of VI was higher in Group 2 (66.1%) than in Group 1 (2.4%) ( p <0.0001). VI was present in 13 (12.9%) of all patients, and amputation in seven (7.9%). The most common localization of amputation was transtibial (n=3).Conclusion: The presence of severe open fractures, VI, and high ISS score can be considered as important factors that increase morbidity and mortality. In extremity traumas, through the secondary blast mechanism, contaminated-fragmented tissue injuries occur. Therefore, we believe that it will be beneficial to apply damage control surgery in places with low socioeconomic level and poor hygienic conditions.
Genome wide association studies for japonica rice resistance to blast in field and controlled conditions
Authors: Volante Andrea , Tondelli Alessandro , Desiderio Francesca , Abbruscato Pamela , Menin Barbara , Biselli Chiara , Casella Laura , Singh Namrata , McCouch Susan R. , Tharreau Didier , Zampieri Elisa , Cattivelli Luigi , Valè Giampiero
Published: March 2020

Background Rice blast, caused by the fungus Pyricularia oryzae , represents the most damaging fungal disease of rice worldwide. Utilization of resistant cultivars represents a practical way to control the disease. Most of the rice varieties cultivated in Europe and several other temperate regions are severely depleted of blast resistance genes, making the identification of resistant sources in genetic background adapted to temperate environments a priority. Given these assumptions, a Genome Wide Association Study (GWAS) for rice blast resistance was undertaken using a panel of 311 temperate/tropical japonica and indica accessions adapted to temperate conditions and genotyped with 37,423 SNP markers. The panel was evaluated for blast resistance in field, under the pressure of the natural blast population, and in growth chamber, using a mixture of three different blast strains. Results The parallel screening identified 11 accessions showing high levels of resistance in the two conditions, representing potential donors of resistance sources harbored in rice genotypes adapted to temperate conditions. A general higher resistance level was observed in tropical with respect to temperate japonica varieties. The GWAS identified 14 Marker-Traits Associations (MTAs), 8 of which discovered under field conditions and 6 under growth chamber screening. Three MTAs were identified in both conditions; five MTAs were specifically detected under field conditions while three for the growth chamber inoculation. Comparative analysis of physical/genetic positions of the MTAs showed that most of them were positionally-related with cloned or mapped blast resistance genes or with candidate genes whose functions were compatible for conferring pathogen resistance. However, for three MTAs no obvious candidates or positional relationships were identified, raising the possibility that these loci harbor previously unidentified blast resistance genes. ConclusionsWe identified 14 MTAs for blast resistance using both field and growth chamber screenings. A total of 11 accessions showing high levels of resistance in both conditions were discovered. Combinations of loci conferring blast resistance were identified in rice accessions adapted to temperate conditions, thus allowing the genetic dissection of affordable resistances present in the panel. The obtained information will provide useful bases for both resistance breeding and further characterization of the highlighted resistance loci.
Qualitative analysis of clinicians’ perspectives on the use of a computerized decision aid in the treatment of psychotic disorders
Authors: Roebroek Lukas , Bruins Jojanneke , Delespaul Philippe A. , Boonstra Albert , Castelein Stynke
Published: March 2020

Background: Clinical decision aids are used in various medical fields to support patients and clinicians when making healthcare decisions. Few attempts have been made to implement such tools in psychiatry. We developed Treatment E-Assist (TREAT); a routine outcome monitoring based computerized clinical decision aid, which generates personalized treatment recommendations in the care of people with psychotic disorders. The aim of this study is to investigate how TREAT is used and evaluated by clinicians and how this tool can be improved.Methods: Clinicians working with TREAT during a clinical trial were asked to participate in semi-structured interviews. The unified theory of acceptance and use of technology (UTAUT) was adopted to structure the interview questions. The transcripts were coded. An inductive thematic analysis was followed to identify the main themes.Results: 13 clinicians (mean age: 49) of which eight psychiatrists and five nurse practitioners, participated in this study. Eight clinicians experienced TREAT as beneficial, whereas five experienced no additional benefits. Thematic analysis revealed five themes about how TREAT was used and evaluated by clinicians, views on TREAT’s visual structuring of routine outcome monitoring results, guideline based treatment recommendations, contextual factors, effects on patients and effects on shared decision-making. Performance and effort expectancy were perceived as high by clinicians. The facilitating conditions were optimal and perceived social influence was low.Conclusion: This article presents a qualitative evaluation by clinicians of a computerized clinical decision aid in psychosis care. TREAT was viewed by most clinicians as beneficial during their consultations. The visual representation of routine outcome monitoring results was well-appreciated and provided input to discuss treatment planning with patients. The treatment recommendations did not change most treatment decisions but supported clinical reasoning. However, some clinicians were unconvinced about TREAT’s benefits. The delivery, applicability and the availability of resources require improvement to increase TREAT’s efficacy. Not all patients responded well to TREAT but the observed facilitation of shared decision-making is promising. All four predictors of the unified theory of acceptance and use of technology were positively evaluated by the majority of clinicians. Clinicians behavioral intentions are expected to be high when implementing TREAT into organizations.
Signs and symptoms do not predict, but may help rule out acute Q fever in favour of other respiratory tract infections, and reduce antibiotics overuse in primary care
Authors: Hackert Volker Heinz , Dukers-Muijrers Nicole H.T.M. , Hoebe Christian J.P.A.
Published: March 2020

Background From early 2009, South Limburg, Netherlands, experienced a massive outbreak of Q fever, overlapping with the influenza A(H1N1)pdm09 pandemic during the second half of the year and affecting approximately 2.9% of the regional population. Acute Q fever shares clinical features with other respiratory conditions. Most symptomatic acute infections are characterized by mild symptoms, or an isolated febrile syndrome. Pneumonia was present in a majority of hospitalized patients during the Dutch 2007-2010 Q fever epidemic. Early empiric doxycycline, guided by signs and symptoms and patient history, should not be delayed awaiting laboratory confirmation, as it may shorten disease and prevent progression to focalized persistent Q fever. We assessed signs’ and symptoms’ association with acute Q fever to guide early empiric treatment in primary care patients. Methods In response to the outbreak, regional primary care and hospital-based specialty physicians tested a total of 1228 subjects for Q fever. Testing activity was bimodal, a first “wave” lasting from March to December 2009, followed by a second “wave” which lasted into 2010 and coincided with peak pandemic influenza activity. We approached all 253 notified acute Q fever cases and a random sample of 457 Q fever negative individuals for signs and symptoms of disease. Using data from 140/229(61.1%) Q fever positive and 194/391(49.6%) Q fever negative respondents from wave 1, we built symptom-based models predictive of Q-fever outcome, validated against each other and against our wave 2 data. Results Our models had moderate AUC scores (0.68% to 0.72%), with low positive (4.6-8.3%), but high negative predictive values (91.7-99.5%). Male sex, fever, and pneumonia were strong positive predictors, while cough was a strong negative predictor of acute Q fever in these models. Conclusion Whereas signs and symptoms of disease do not appear to predict acute Q fever, they may help rule it out in favour of other respiratory conditions, prompting a delayed or non-prescribing approach instead of early empiric doxycycline in primary care patients with non-severe presentations. Signs and symptoms thus may help reduce the overuse of antibiotics in primary care during and following outbreaks of Q fever.
Expression of FAM83H and ZNF16 are associated with shorter survival of patients with gallbladder carcinoma
Authors: Ahn Sung Woo , Ahn Ae-Ri , Ha Sang Hoon , Hussein Usama Khamis , Yang Jae Do , Kim Kyoung Min , Park Ho Sung , Park See-Hyoung , Yu Hee Chul , Jang Kyu Yun
Published: March 2020

BackgroundRecently, FAM83H was reported to have roles in cancer progression in conjunction with oncogenic molecules such as MYC and b-catenin. Moreover, the data from the public database indicates a molecular relationship between FAM83H and zinc finger proteins, especially between FAM83H and ZNF16. However, studies on FAM83H and ZNF16 in gallbladder cancer have been limited. MethodsThis study investigated the expression of FAM83H and ZNF16 in 105 gallbladder carcinomas. ResultsIn human gallbladder carcinomas, immunohistochemical expression of FAM83H was significantly associated with ZNF16 expression. In univariate analysis, nuclear and cytoplasmic expression of FAM83H or ZNF16 were significantly associated with shorter survival of gallbladder carcinoma patients. Multivariate analysis revealed the nuclear expression of FAM83H as an independent indicator of poor prognosis of overall survival (p = 0.005) and relapse-free survival (p = 0.005) of gallbladder carcinoma patients. Moreover, co-expression patterns of nuclear FAM83H and ZNF16 were also independent indicators of shorter survival of gallbladder carcinoma patients (overall survival; p < 0.001, relapse-free survival; p < 0.001). ConclusionsThis study suggests FAM83H and ZNF16 are associated with the progression of gallbladder carcinoma, and the expressions of FAM83H and ZNF16 might be novel prognostic indicators of gallbladder carcinoma patients.
Interaction Between HIF-1α and Notch Signaling Pathways in Nucleus Pulposus Cells of Patients with Modic Changes
Authors: Xiong Zekang , Guo Xiaodong , Zheng Jin , Ding Jun , Zhou Jinge , Yao Sheng
Published: March 2020

Background The HIF-1α/Notch signaling pathway has been shown to regulate proliferation, apoptosis, and metabolism in the intervertebral disc (IVD). The NP is an important structure adjacent to the disc. However, the roles of HIF1α and Notch signaling pathways in NP cells of patients with different Modic changes (MCs) are unclear. The purpose of this research was to assess the expression and association of HIF-1α and components of the Notch pathway in nucleus pulposus (NP) tissue of patients with various MCs. Methods Eighty-five surgical NP tissue samples were obtained from patients undergoing microdiscectomy procedures for the treatment of low back and root pain caused by prolapse of the IVD. The NP tissues were divided into four groups based on the adjacent endplate degeneration: MC I, II, III, and negative MC groups. The expression of HIF-1α and Notch-related components were measured and compared. Results The expression of HIF-1α, Notch1, and Notch2 were gradually increased in the MC I and MC II groups compared with that of the negative MC group. Meanwhile, HIF-1α and Notch-related components were rarely detected in MC III group. Conclusions The expression of HIF-1α/Notch is increased in the NP cells of patients with MC I and MC II. Application of the association between HIF-1α/Notch signaling pathway could be promising target for clinical diagnosis and treatment of disc degeneration in MC patients.
Complications of bone transport technique using the Ilizarov method in the lower extremity: a retrospective analysis of 282 consecutive cases over 10 years
Authors: Liu Yanshi , Yushan Maimaiaili , Liu Zhenhui , Liu Jialin , Ma Chuang , Ahemaitijiang Yusufu
Published: March 2020

Background: The treatment of large bone defects in lower limbs is a serious challenge for orthopedic surgeons and patients. The bone transport technique according to the Ilizarov method characterized with versatile abilities and has become the main option for the reconstruction of bone defect. However, inevitable difficulties as complications related to bone transport technique have been reported by many studies. Complications which could affect on the clinical outcomes remain a major concern. The purpose of this study was to evaluate the effectiveness and complications of bone transport technique using Ilizarov method in the treatment of bone defect in lower extremity.Methods: The study was conducted on 282 patients who underwent bone transport procedures using Ilizarov method at our institution from January 2007 to June 2017. Patient’s demographic data, complications and clinical outcomes at two years follow-up were collected and retrospectively analyzed. All difficulties that related to bone transport were documented according to Paley’s classification. The clinical outcomes were evaluated using Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at last clinical visit.Results: There were 243 male and 39 females with a mean age of 40 years (range 18-65 years). The mean defect was 6.56±2.15 cm, whereas single level transport in 221 cases and double level transport in 61 cases. A total of 189 problems, 166 obstacles and 406 complications (257 minor and 149 major complications) were observed，the average complication rate per patients consists of 0.91 minor and 0.53 major complications. The top five complications were pin-site infection (65.96%), axial deviation (40.78%), joint stiffness (23.76%), soft tissue incarceration (22.34%) and delayed union of the docking site (13.48%).The ASAMI bony result was excellent in 233 patients, good in 32, fair in 5 and poor in 12. The ASAMI functional result was excellent in 136 patients, good in 88, fair in 47, poor in 11 and failure in 0.Conclusion: Bone transport is a reliable method for reconstruction of bone defects in the femur and tibia caused by variety of reasons. Particular attention, patient’s compliance and experience of the surgeon contribute the satisfactory results.
Aveolar Macrophage Activation and Cytokine Storm in the Pathogenesis of Severe COVID-19
Authors: Wang Chaofu , Xie Jing , Zhao Lei , Fei Xiaochun , Zhang Heng , Tan Yun , Zhou Luting , Liu Zhenhua , Ren Yong , Yuan Ling , Zhang Yu , Zhang Jinsheng , Liang Liwei , Chen Xinwei , Liu Xin , Wang Peng , Han Xiao , Weng Xiangqin , Chen Ying , Yu Ting , Zhang Xinxin , Cai Jun , Chen Rong , Shi Zhengli , Bian Xiuwu
Published: March 2020

The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.
Tumor Response Prediction in 90Y Radioembolization with PET-based Radiomics Features and Absorbed Dose Metrics
Authors: Wei Lise , Cui Can , Xu Jiarui , Kaza Ravi , Naqa Issam El , Dewaraja Yuni K
Published: March 2020

Purpose Evaluate whether lesion radiomics features and absorbed dose metrics extracted from post-therapy 90 Y PET can be integrated to better predict outcome in microsphere radioembolization of liver malignancies. Methods Given the noisy nature of 90 Y PET, first, a liver phantom study with repeated acquisitions and varying reconstruction parameters was used to identify a subset of robust radiomics features for the patient analysis. In 36 radioembolization procedures, 90 Y PET/CT was performed within a couple of hours to extract 46 radiomics features and estimate absorbed dose in 105 primary and metastatic liver lesions. Robust radiomics modeling was based on bootstrapped multivariate logistic regression with shrinkage regularization (LASSO) and Cox regression with LASSO. Nested cross-validation and bootstrap resampling were used for optimal parameter/feature selection and for guarding against overfitting risks. Spearman rank correlation was used to analyze feature associations. Area under the receiver-operating characteristics curve (AUC) was used for lesion response (at first follow-up) analysis while Kaplan-Meier plots and c-index were used to assess progression model performance. Models with absorbed dose only, radiomics only and combined models were developed to predict lesion outcome. Results The phantom study identified 15/46 reproducible and robust radiomics features that were subsequently used in the patient models. A lesion response model with zone percentage (ZP) and mean absorbed dose achieved an AUC of 0.729 (95%CI: 0.702-0.758) and a progression model with zone size nonuniformity (ZSN) and absorbed dose achieved a c-index of 0.803 (95% CI: 0.790-0.815) on nested cross validation (CV). The combined models outperformed the radiomics only and absorbed dose only models. Conclusion We have developed new lesion-level response and progression models using textural radiomics features, derived from 90 Y PET combined with mean absorbed dose for predicting outcome in radioembolization. These encouraging results may need further validation in independent datasets prior to clinical adoption.
Genome-wide analysis of the AREB/ABF gene lineage in land plants and functional analysis of TaABF3 in Arabidopsis
Authors: Li Fangfang , Mei Fangming , Zhang Yifang , Li Shumin , Mao Hude
Published: March 2020

Background: Previous studies have shown that ABFs (abscisic acid-responsive transcription factors) are important ABA-signaling components that participate in abiotic stress response. However, little is known about the function of ABFs in Triticum aestivum. In addition, although various ABFs have been identified in other species, the phylogenetic relationship between ABF transcription factors has not been systemically investigated in land plants. Results: In this study, we systemically collected ABFs from land plants and analyzed the phylogenetic relationship of these ABF genes. The ABF genes are present in all the land plants we investigated, including moss, lycophyte, monocots, and eudicots. Furthermore, these ABF genes are phylogenetically divided into seven subgroups, differentiations that are supported by variation in the gene structure, protein properties, and motif patterns. We further demonstrated that the expression of ABF genes varies among different tissues and developmental stages, and are induced by one or more environmental stresses. Furthermore, we found that three wheat ABFs (TaABF1, TaABF2, and TaABF3) were significantly induced by drought stress. Compared with wild-type (WT) plants, transgenic Arabidopsis plants overexpressing TaABF3 displayed enhanced drought tolerance. Conclusions: These results provide important ground work for understanding the phylogenetic relationships between plant ABF genes. Our results also indicate that TaABFs may participate in regulating plant response to abiotic stresses.
High resolution computed tomography for the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia: a study from multiple medical centers in western China
Authors: Li Hong-Wei , Zhuo Li-Hua , Yan Gao-Wu , Wang Ji-Sheng , Huang Guo-Ping , Li Jia-Bing , Fang-Zhang  , Long Yong-Jun , Deng Li-Hua , Su Li-Ping , Yao Hong-Chao , Das Sushant-Kumar , Li Yong , Yang Han-Feng , Du Yong
Published: March 2020

Objective: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia. Methods: 72 patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features. Results: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in sixteen (22.22%), and in both lungs, with "white lung "manifestations in four (5.56%). Subpleural multifocal consolidation was predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18patients, of which eight had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), in all of whom it was mild and randomly distributed. In addition, both lungs of 28 patients had two or three CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05). Conclusion: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia.Authors Hong-Wei Li, Li-Hua Zhuo, Gao-Wu Yan contributed equally to this work.
Epidemiological Characteristics of 417 patients infected with COVID-19 and 368 discharged cases among them in Shenzhen City, China
Authors: Yuan Bo , An Ya-Wen , Chen Yong-Xin , Yang Jing , Wang Jian-Chun , Li Wei-Xin , Wang Cheng , Song Shuo , Liu Han-Qing
Published: March 2020

The outbreak of Coronavirus Disease 2019 (COVID-19) is getting worse every day all over the world. The present study aimed to review the epidemiological characteristics of patients infected with COVID-19 in Shenzhen city, a super megacity of China, to provide some references for fighting to the coronavirus. We collected data of 417 patients with laboratory-confirmed COVID-19 of Shenzhen through March 7th, 2020. The epidemiological characteristics of the patients were analyzed. Besides, we collected the governmental measures of Shenzhen city, and the the dynamic changes of the epidemic outbreak. Governmental strategies such as early detection, early hospitalization and popular science etc. are effective for the prevention and control of the epidemic. Nearly 80% confirmed patients with COVID-19 in Shenzhen were in normal or mild conditions, and the mortality was less than 1%. Age, gender, exposure to source of transmission within 14 days and basic diseases are major risk factors for severe patients. Patients in characters of elder, male, with exposure of Wuhan and carried basic diseases had higher risk to be in severe condition (P<0.01; P<0.001). There were 368 patients discharged from hospital by the end of March 7th, 2020. Patients in severe conditions took more time from onset to discharge (P<0.001), so as those elder one (P<0.001) or who carried basic diseases (P<0.01). The differences of epidemiological characteristics between children and the elderly are still not clear. The nucleic acid test of some discharged patients returned to positive again, and the potential mechanisms need to be further explored. In conclusion, timely administrative intervention is necessary for prevention and control of the COVID-19 outbreak. Patients in characters of elder, male and carried basic diseases worthy more attention. The management of discharged patients, especially the investigation of the recurrence of positive SARS-CoV-2 RNA will be the focus on for the next step. Authors Bo Yuan and Ya-Wen An contributed equally to this work.
Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus
Authors: Cross Robert W. , Bornholdt Zachary A. , Prasad Abhishek N. , Geisbert Joan B. , Borisevich Viktoriya , Agans Krystle N. , Deer Daniel J. , Melody Kevin , Fenton Karla A. , Feldmann Heinz , Sprecher Armand , Zeitlin Larry , Geisbert Thomas W.
Published: March 2020

A replication-competent, vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic1. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP showed promise in animals and EBOV patients when administered therapeutically2-6. Given the large number of at-risk humans being prophylactically vaccinated with rVSV-ZEBOV there is uncertainty regarding whether vaccination would preclude use of antibody treatments in the event of a known exposure of a recent vaccinee. To model a worst-case scenario, we performed a study using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. One day after vaccination, animals were challenged with a uniformly lethal dose of EBOV. Five vaccinated animals and five unvaccinated animals were then treated with the anti-EBOV GP mAb-based therapeutic MIL77 starting 3 days postexposure. Additionally, five vaccinated macaques received no therapeutic intervention. All five macaques that were vaccinated and subsequently treated with MIL77 showed no evidence of clinical illness and survived challenge. In contrast, all five animals that only received the rVSV-ZEBOV vaccine became ill and 2/5 survived; all five macaques that only received MIL77 only also became ill and 4/5 survived. Enhanced efficacy of vaccinated animals that were treated with MIL77 was associated with delayed EBOV viremia attributed to the vaccine. These results suggest that rVSV-ZEBOV augments immunotherapy.Authors Robert W. Cross, Zachary A. Bornholdt, and Abhishek N. Prasad contributed equally to this work.