bluuebunny/crossref_metadata_2025 huggingface dataset:
Ergodic Stationary Distribution of a Stochastic Hepatitis B Epidemic Model with Interval-Valued Parameters and Compensated Poisson Process
Authors: Kiouach Driss , Sabbar Yassine
Published: January 2020

Hepatitis B epidemic was and is still a rich subject that sparks the interest of epidemiological researchers. The dynamics of this epidemic is often modeled by a system with constant parameters. In reality, the parameters associated with the Hepatitis B model are not certain, but the interval in which it belongs to can readily be determined. Our paper focuses on an imprecise Hepatitis B model perturbed by Lévy noise due to unexpected environmental disturbances. This model has a global positive solution. Under an appropriate assumption, we prove the existence of a unique ergodic stationary distribution by using the mutually exclusive possibilities lemma demonstrated by Stettner in 1986. Our main effort is to establish an almost perfect condition for the existence of the stationary distribution. Numerical simulations are introduced to illustrate the analytical results.
Survey and Diagnostic Challenges after Transmission-Stop: Confirming Elimination of Schistosomiasis haematobium in Morocco
Authors: Fatima Amarir , Abdelaali Balahbib , Corstjens Paul L. A. M. , Abderrahim Sadak , El Bachir Adlaoui , Mohamed Rhajaoui
Published: January 2020

Clinical cases of Moroccan residents have been recorded since 2004, indicating successful interruption of transmission of S. haematobium infection at national level. The first national survey initiated in 2009 for Schistosomiasis haematobium among children born after 2004, applied diagnostic test was the HAMA-EITB, based on the Western blot technology, and molecular malacological diagnostic tools clearly confirm transmission stop. In 2015, a recent, small survey utilizing an HAI, ELISA tests and an ultrasensitive antigen test, FTCUP CAA, in a group of individual with a past history of infection. However, obviously follow-up surveys to prevent reemergency and for certification of the schistosomiasis elimination require vigilant diagnosis strategies. Here we discuss diagnosis story line in the national laboratory and challenges based on the available tools in relation to their clinical parameters (sensitivity/specificity; Sn/Sp), practicability and associated costs. When transmission stop has been achieved, survey cost and speed are likely to benefit from cost effective pooling strategies and ultrasensitive assays indicating active infection in all potential risk groups. Similarly molecular pooling strategies to monitor infections in the snail vectors.
Analysis of Clinical Factors, Bacterial Genotyping, and Drug Resistance for Spinal Tuberculosis in South‐Central China
Authors: Liu Zheng , Li Weiwei , Zhang Yilu , Wu Yunqi , Xiao Xiao , Sun Zhicheng , Yang Yan , Hu Wenkai , Wang Xiyang , Zeng Hao
Published: January 2020

Spinal tuberculosis (STB), which is the most frequent and serious form of skeletal TB, is seriously harmful to a patient’s life. However, very little research has been conducted on clinical isolates of STB. The purpose of this study was to genotype clinical isolates of Mycobacterium tuberculosis (MTB) from patients with STB, investigate their drug resistance profiles, and determine whether the genotypes and drug resistance patterns share any relationships with the demographic and clinical features of the patients. Preliminary species identification of the MTB strains was performed using a TCH/PNB culture method and multilocus polymerase chain reactions. Of the specimens collected from 85 hospital in‐patients with STB at Xiangya Hospital, China, the 56 culture‐positive MTB strains we identified were genotyped by spoligotyping. The strains were tested for resistance to anti‐tuberculosis drugs (ATDs), and the demographic and clinical features of the patients were analyzed in combination with the genotyping and drug resistance results. Of the 56, cases, 53 involved M. tuberculosis and 3 involved M. bovis. Spoligotyping revealed 27 Beijing‐type cases and 29 nonBeijing cases. When patients with STB were relapsing or experiencing systemic toxicity signs/symptoms (STS), the Beijing MTB‐type strains predominated (p < 0.05), but when the patients were receiving initial treatment or lacked STS, the nonBeijing type MTB strains dominated. The Beijing and nonBeijing types differed in their resistance patterns to 8 ATDs, and the resistance rate of the Beijing type was higher than that of the nonBeijing type (p < 0.05). The bacteriological features of STB, including genotype and drug resistance, shared close relationships with the clinical features of patients with STB. Our data provide a reference for the diagnosis and treatment of STB.
The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer
Authors: Cristea Sandra , Coles Garry L. , Hornburg Daniel , Gershkovitz Maya , Arand Julia , Cao Siqi , Sen Triparna , Williamson Stuart C. , Kim Jun W. , Drainas Alexandros P. , He Andrew , Cam Laurent Le , Byers Lauren Averett , Snyder Michael P. , Contrepois Kévin , Sage Julien
Published: January 2020

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5–ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in vitro and in vivo. Transcriptomics analyses identified a role for the MEK5–ERK5 axis in the metabolism of SCLC cells, including lipid metabolism. In-depth lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, including the mevalonate pathway that controls cholesterol synthesis. Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition of the mevalonate pathway by statins. These data identify a new MEK5–ERK5–lipid metabolism axis that promotes the growth of SCLC.

Significance:

This study is the first to investigate MEK5 and ERK5 in SCLC, linking the activity of these two kinases to the control of cell survival and lipid metabolism.
Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study
Authors: Burke Michael J. , Kostadinov Rumen , Sposto Richard , Gore Lia , Kelley Shannon M. , Rabik Cara , Trepel Jane B. , Lee Min-Jung , Yuno Akira , Lee Sunmin , Bhojwani Deepa , Jeha Sima , Chang Bill H. , Sulis Maria Luisa , Hermiston Michelle L. , Gaynon Paul , Huynh Van , Verma Anupam , Gardner Rebecca , Heym Kenneth M. , Dennis Robyn M. , Ziegler David S. , Laetsch Theodore W. , Oesterheld Javier E. , Dubois Steven G. , Pollard Jessica A. , Glade-Bender Julia , Cooper Todd M. , Kaplan Joel A. , Farooqi Midhat S. , Yoo Byunggil , Guest Erin , Wayne Alan S. , Brown Patrick A.
Published: January 2020

Purpose:

Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution.

Patients and Methods:

We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range, 1–21) were treated in this trial.

Results:

The most common grade 3–4 toxicities included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%). Three subjects experienced dose-limiting toxicities, which included cholestasis, steatosis, and hyperbilirubinemia (n = 1); seizure, somnolence, and delirium (n = 1); and pneumonitis, hypoxia, and hyperbilirubinemia (n = 1). Infectious complications were common with 17 of 23 (74%) subjects experiencing grade ≥3 infections including invasive fungal infections in 35% (8/23). Nine subjects (39%) achieved a complete response (CR + CR without platelet recovery + CR without neutrophil recovery) and five had stable disease (22%). Nine (39%) subjects were not evaluable for response, primarily due to treatment-related toxicities. Correlative pharmacodynamics demonstrated potent in vivo modulation of epigenetic marks, and modulation of biologic pathways associated with functional antileukemic effects.

Conclusions:

Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities. This study is registered at http://www.clinicaltrials.gov as NCT01483690.
First-in-Human Phase I Study of ABBV-838, an Antibody–Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma
Authors: Vij Ravi , Nath Rajneesh , Afar Daniel E.H. , Mateos María-Victoria , Berdeja Jesús G. , Raab Marc S. , Guenther Andreas , Martínez-López Joaquín , Jakubowiak Andrzej J. , Leleu Xavier , Weisel Katja , Wong Shekman , Gulbranson Scott , Sheridan James P. , Reddy Anita , Paiva Bruno , Singhal Anil , San-Miguel Jesús F. , Moreau Philippe
Published: January 2020

Purpose:

ABBV-838 is an antibody–drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM).

Patients and Methods:

Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel.

Results:

As of March 2017, 75 patients received at least one dose of ABBV-838. The most common any-grade treatment-emergent adverse events (TEAE) were neutropenia and anemia (28.0% each), fatigue (26.7%), and nausea (25.3%). Grade 3/4/5 TEAEs were reported in 73.3% of patients across all treatment groups; most common were neutropenia (20.0%), anemia (18.7%), and leukopenia (13.3%). Grade 3/4/5 ABBV-838–related TEAEs were reported by 40.0% of patients across all treatment groups. Overall, 4.0% of patients experienced TEAEs leading to death, none ABBV-838 related. The MTD was not reached; the selected recommended dose for the expansion cohort was 5.0 mg/kg Q3W. Pharmacokinetic analysis showed that exposure was approximately dose proportional. The overall response rate was 10.7%; very good partial responses and partial responses were achieved by 2 (2.7%) and 6 (8.0%) patients, respectively.

Conclusions:

These results demonstrate that ABBV-838 is safe and well-tolerated in patients with RRMM with a very limited efficacy.
CDKN1B Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer
Authors: Faisal Farzana A. , Murali Sanjana , Kaur Harsimar , Vidotto Thiago , Guedes Liana B. , Salles Daniela Correia , Kothari Vishal , Tosoian Jeffrey J. , Han Sumin , Hovelson Daniel H. , Hu Kevin , Spratt Daniel E. , Baras Alexander S. , Tomlins Scott A. , Schaeffer Edward M. , Lotan Tamara L.
Published: January 2020

Purpose:

The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population.

Experimental Design:

Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent of the genome with copy-number alterations (PGA). Cox proportional hazards analyses assessed the association of genomic alterations with risk of metastasis.

Results:

At RP, 71% (145/205) of patients had grade group ≥3 disease, and 49% (99/202) were non–organ confined. The median PGA was 3.7% (IQR = 0.9%–9.4%) and differed by pathologic grade (P < 0.001) and stage (P = 0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had increased risks of metastasis (multivariable: HR = 13.45; 95% CI, 2.55–70.86; P = 0.002). The most common somatic mutations were SPOP (11.2%), FOXA1 (8.3%), and TP53 (3.9%). The most common loci altered at the copy number level were CDKN1B (6.3%), CHD1 (4.4%), and PTEN (3.4%). TP53 mutations and deep deletions in CDKN1B were associated with increased risks of metastasis on multivariable analyses (TP53: HR = 9.5; 95% CI, 2.2–40.6; P = 0.002; CDKN1B: HR = 6.7; 95% CI, 1.3–35.2; P = 0.026).

Conclusions:

Overall, PGA, somatic TP53 mutations, and a novel finding of deep deletions in CDKN1B were associated with poor prognosis in AA men. These findings require confirmation in additional AA cohorts.
Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial
Authors: Graillon Thomas , Sanson Marc , Campello Chantal , Idbaih Ahmed , Peyre Matthieu , Peyrière Hadrien , Basset Noémie , Autran Didier , Roche Catherine , Kalamarides Michel , Roche Pierre-Hugues , Fuentes Stéphane , Tabouret Emeline , Barrie Maryline , Cohen Anita , Honoré Stéphane , Boucekine Mohamed , Baumstarck Karine , Figarella-Branger Dominique , Barlier Anne , Dufour Henry , Chinot Olivier Louis
Published: January 2020

Purpose:

Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas.

Patients and Methods:

Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1–28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety.

Results:

A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%–73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%–97.4%) and 75% (95% CI, 50.0%–88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003).

Conclusions:

The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.
Preclinical Activity of JNJ-7957, a Novel BCMA×CD3 Bispecific Antibody for the Treatment of Multiple Myeloma, Is Potentiated by Daratumumab
Authors: Frerichs Kristine A. , Broekmans Marloes E.C. , Marin Soto Jhon A. , van Kessel Berris , Heymans Martijn W. , Holthof Lisa C. , Verkleij Christie P.M. , Boominathan Rengasamy , Vaidya Bhavesh , Sendecki Jocelyn , Axel Amy , Gaudet Francois , Pillarisetti Kodandaram , Zweegman Sonja , Adams Homer C. , Mutis Tuna , van de Donk Niels W.C.J.
Published: January 2020

Purpose:

Multiple myeloma (MM) patients with disease refractory to all available drugs have a poor outcome, indicating the need for new agents with novel mechanisms of action.

Experimental Design:

We evaluated the anti-MM activity of the fully human BCMA×CD3 bispecific antibody JNJ-7957 in cell lines and bone marrow (BM) samples. The impact of several tumor- and host-related factors on sensitivity to JNJ-7957 therapy was also evaluated.

Results:

We show that JNJ-7957 has potent activity against 4 MM cell lines, against tumor cells in 48 of 49 BM samples obtained from MM patients, and in 5 of 6 BM samples obtained from primary plasma cell leukemia patients. JNJ-7957 activity was significantly enhanced in patients with prior daratumumab treatment, which was partially due to enhanced killing capacity of daratumumab-exposed effector cells. BCMA expression did not affect activity of JNJ-7957. High T-cell frequencies and high effector:target ratios were associated with improved JNJ-7957–mediated lysis of MM cells. The PD-1/PD-L1 axis had a modest negative impact on JNJ-7957 activity against tumor cells from daratumumab-naïve MM patients. Soluble BCMA impaired the ability of JNJ-7957 to kill MM cells, although higher concentrations were able to overcome this negative effect.

Conclusions:

JNJ-7957 effectively kills MM cells ex vivo, including those from heavily pretreated MM patients, whereby several components of the immunosuppressive BM microenvironment had only modest effects on its killing capacity. Our findings support the ongoing trial with JNJ-7957 as single agent and provide the preclinical rationale for evaluating JNJ-7957 in combination with daratumumab in MM.
Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort
Authors: Song Nan , Li Zhenghong , Qin Na , Howell Carrie R. , Wilson Carmen L. , Easton John , Mulder Heather L. , Edmonson Michael N. , Rusch Michael C. , Zhang Jinghui , Hudson Melissa M. , Yasui Yutaka , Robison Leslie L. , Ness Kirsten K. , Wang Zhaoming
Published: January 2020

Purpose:

We aimed to analyze and compare leukocyte telomere length (LTL) and age-dependent LTL attrition between childhood cancer survivors and noncancer controls, and to evaluate the associations of LTL with treatment exposures, chronic health conditions (CHC), and health behaviors among survivors.

Experimental Design:

We included 2,427 survivors and 293 noncancer controls of European ancestry, drawn from the participants in St. Jude Lifetime Cohort Study (SJLIFE), a retrospective hospital-based study with prospective follow-up (2007–2016). Common nonneoplastic CHCs (59 types) and subsequent malignant neoplasms (5 types) were clinically assessed. LTL was measured with whole-genome sequencing data.

Results:

After adjusting for age at DNA sampling, gender, genetic risk score based on 9 SNPs known to be associated with telomere length, and eigenvectors, LTL among survivors was significantly shorter both overall [adjusted mean (AM) = 6.20 kb; SE = 0.03 kb] and across diagnoses than controls (AM = 6.69 kb; SE = 0.07 kb). Among survivors, specific treatment exposures associated with shorter LTL included chest or abdominal irradiation, glucocorticoid, and vincristine chemotherapies. Significant negative associations of LTL with 14 different CHCs, and a positive association with subsequent thyroid cancer occurring out of irradiation field were identified. Health behaviors were significantly associated with LTL among survivors aged 18 to 35 years (Ptrend = 0.03).

Conclusions:

LTL is significantly shorter among childhood cancer survivors than noncancer controls, and is associated with CHCs and health behaviors, suggesting LTL as an aging biomarker may be a potential mechanistic target for future intervention studies designed to prevent or delay onset of CHCs in childhood cancer survivors.

See related commentary by Walsh, p. 2281
Are Obesity Indices Useful for Detecting Subclinical Atheromatosis in a Middle-Aged Population?
Authors: Sánchez Enric , Sánchez Marta , Betriu Àngels , Rius Ferran , Torres Gerard , Purroy Francesc , Pamplona Reinald , Ortega Marta , López-Cano Carolina , Hernández Marta , Bueno Marta , Fernández Elvira , Salvador Javier , Lecube Albert ,   ILERVAS project collaborators
Published: January 2020

Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53–63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra – Body Adiposity Estimator [CUN-BAE], and Deurenberg’s formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora’s equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. ­Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
Vaccination in Patients with Inflammatory Bowel Diseases
Authors: Manser Christine N. , Maillard Michel H. , Rogler Gerhard , Schreiner Philipp , Rieder Florian , Bühler Silja ,   on behalf of Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology
Published: January 2020

During the course of disease, a majority of inflammatory bowel disease (IBD) patients requires long-term immunosuppressive therapy with either immunomodulatory agents, biologics, or newer immunosuppressive therapies such as Vedolizumab, a selective α4β7 inhibitor, Ustekinumab, an IL 12/23 p40 inhibitor, or the Janus kinase inhibitor Tofacitinib. Due to this, they are at increased risk for infectious diseases, many of which are possible to prevent by vaccination. This review focuses on recommended vaccinations in IBD patients and stresses special issues which have to be paid attention to. The aim of the review is to increase gastroenterologists’ awareness of the importance of vaccination and to stress why especially the gastroenterologist should assess the vaccination status of the patient and initiate vaccination as soon as diagnosis is established.
Complement C3 and Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease Patients: A Pilot Study
Authors: Pan Binbin , Wan Xin , Ma Mengqing , Cao Changchun
Published: January 2020

Context: Evidences have suggested complement C3 is a biomarker for nonalcoholic fatty liver disease (NAFLD) in the general population. Objective: The present study was conducted to explore the predictive function of C3 for NAFLD in chronic kidney disease (CKD) patients. Design, Setting, and Participants: CKD patients were recruited for evaluation of their liver function, kidney function, serum lipids, glycated hemoglobin, blood, and immune function. The glomerular filtration rate was calculated using the CKD-EPI equation. NAFLD was diagnosed according to predefined ultrasonographic criteria. Results: A total of 648 consecutive CKD patients were included, with 216 (33.3%) patients diagnosed with NAFLD. The NAFLD group had significant higher levels of serum protein, serum albumin, triglycerides, glycated hemoglobin, complement C3, hemoglobin (p = 0.001), alanine aminotransferase (p = 0.002), estimated glomerular filtration rate (p = 0.007), and C4 (p = 0.043) and lower levels of cystatin C, β2-microglobulin, proteinuria (p = 0.001), and high-density lipoprotein cholesterol (p = 0.008). In a logistic regression model, only complement C3 (OR = 1.003; 95% CI 1.002–1.004, p = 0.001) was associated with a higher likelihood of being diagnosed with NAFLD. Finally, we constructed ROC curves for complement C3 for prediction of having NAFLD. The best cut-off for complement C3 was 993.5 mg/L and it yielded a sensitivity of 63.9% and a specificity of 70.1%. Conclusion: Our study revealed that complement C3 can be used as a surrogate biomarker of NAFLD in CKD patients.
Protective Effect of Fluoride Varnish Containing Trimetaphosphate against Dentin Erosion and Erosion/Abrasion: An in vitro Study
Authors: Danelon Marcelle , Pessan Juliano Pelim , Prado Kamila Miranda , Ramos Jéssica Paula , Emerenciano Nayara Gonçalves , Moretto Marcelo Juliano , Martinhon Cleide Cristina Rodrigues , Delbem Alberto Carlos Botazzo
Published: January 2020

This in vitro study evaluated the protective effect of fluoride varnishes containing sodium trimetaphosphate (TMP) against dentin erosion and abrasion. Specimens of coronal dentin were divided into: placebo, 2.5% NaF, 5% NaF, 2.5% NaF + 5% TMP, and 5% NaF + 5% TMP groups (n =24/group). After single application of the varnishes, the samples were immersed in citric acid (0.05 mol/L, pH = 3.2, 5 min) followed or not by brushing, and the dentin wear was assessed after 5 days. Varnishes containing fluoride + TMP led to the lowest wear. TMP varnishes showed a superior effect against dentin erosive wear.
Usefulness of the ACTEL Score to Predict Atrial Fibrillation in Patients with Cryptogenic Stroke
Authors: Muscari Antonio , Barone Pietro , Faccioli Luca , Ghinelli Marco , Pastore Trossello Marco , Puddu Giovanni M. , Spinardi Luca , Zoli Marco
Published: January 2020

Introduction: To assess the probability of undetected atrial fibrillation (AF) in patients with ischemic stroke, we previously compared patients who were first diagnosed with AF with patients with large or small artery disease and obtained the MrWALLETS 8-item scoring system. In the present study, we utilized cryptogenic strokes (CS) as the control group, as AF is normally sought among CS patients. Methods: We retrospectively examined 191 ischemic stroke patients (72.5 ± 12.6 years), 68 with first diagnosed AF and 123 with CS, who had undergone 2 brain CT scans, echocardiography, carotid/vertebral ultrasound, continuous electrocardiogram monitoring and anamnestic/laboratory search for cardiovascular risk factors. Results: In logistic regression, 5 variables were independently associated with AF, forming the “ACTEL” score: Age ≥75 years (OR 2.42, 95% CI 1.18–4.96, p = 0.02; +1 point); hyperCholesterolemia (OR 0.38, 95% CI 0.18–0.78, p = 0.009; –1 point); Tricuspid regurgitation ≥ mild-to-moderate (OR 4.99, 95% CI 1.63–15.27, p = 0.005; +1 point); left ventricular End-diastolic volume <65 mL (OR 7.43, 95% CI 2.44–22.6, p = 0.0004; +1 point); Left atrium ≥4 cm (OR 4.57, 95% CI 1.97–10.62, p = 0.0004; +1 point). The algebraic sum of these points may range from –1 to +4. For AF identification, the area under the receiver operating characteristic curve was 0.80 (95% CI 0.73–0.87). With a cutoff of ≥2, positive predictive value was 80.8%, specificity 92.7% and sensitivity 55.9%. Conclusions: The ACTEL score, a simplified and improved version of the MrWALLETS score, allows the identification of patients with first diagnosed AF, in the context of CSs, with a high positive predictive value.
Molecular Blood Group Screening in Donors from Arabian Countries and Iran Using High-Throughput MALDI-TOF Mass Spectrometry and PCR-SSP
Authors: Flesch Brigitte Katharina , Scherer Vanessa , Just Burkhard , Opitz Andreas , Ochmann Oswin , Janson Anne , Steitz Monika , Zeiler Thomas
Published: January 2020

Background and Aims: Only little is known about blood groups other than ABO blood groups and Rhesus factors in Arabian countries and Iran. During the last years, increased migration to Central Europe has put a focus on the question how to guarantee blood supply for patients from these countries, particularly because hemoglobinopathies with the need of regular blood support are more frequent in patients from that region. Therefore, blood group allele frequencies should be determined in individuals from Arabian countries and Iran by molecular typing and compared to a German rare donor panel. Methods: 1,111 samples including 800 individuals from Syria, 147 from Iran, 123 from the Arabian Peninsula, and 41 from Northern African countries were included in a MALDI-TOF MS assay to detect polymorphisms coding for Kk, Fy(a/b), Fynull, Cw, Jk(a/b), Jo(a+/a–), Lu(a/b), Lu(8/14), Ss, Do(a/b), Co(a/b), In(a/b), Js(a/b), Kp(a/b), and variant alleles RHCE*c.697C>G and RHCE*c.733C>G. Yt(a/b), S–s–U–, Velnull, Conull, and RHCE*c.667G>T were tested by PCR-SSP. Results: Of the Arabian donors, 2% were homozygous for the FY*02.01N allele (Fynull), and 15.7% carried the heterozygous mutation. However, 0.8% of the German donors also carried 1 copy of the allele. 3.6% of all and 29.3% of Northern African donors were heterozygous for the RHCE*c.733C>G substitution, 0.4% of the Syrian probands were heterozygous for DO*01/DO*01.-05, a genotype that was lacking in German donors. Whereas the KEL*02.06 allele coding for the Js(a) phenotype was missing in Germans; 0.8% of the Syrian donors carried 1 copy of this allele. 1.8% of the Syrian but only 0.3% of the German donors were negative for YT*01. One donor from Northern Africa homo­zygously carried the GYPB*270+5g>tmutation, inducing the S–s–U+w phenotype, and in 2 German donors a GYPB*c.161G>A exchange, which induces the Mit+ phenotype, caused a GYPB*03 allele dropout in the MALDI assay. The overall failure rate of the Arabian panel was 0.4%. Conclusions: Some blood group alleles that are largely lacking in Europeans but had been described in African individuals are present in Arabian populations at a somewhat lower frequency. In single cases, it could be challenging to provide immunized Arabian patients with compatible blood.
Higher Postdialysis Lactic Acid Is Associated with Postdialysis Fatigue in Maintenance of Hemodialysis Patients
Authors: Zu Yuan , Lu Xiangxue , Yu Qian , Yu Ling , Li Han , Wang Shixiang
Published: January 2020

Background: Postdialysis fatigue (PDF) is not an unusual symptom among hemodialysis (HD) patients; however, its causes remain unclear. The aim of this study was to analyze the factors responsible for PDF in maintenance HD patients. Methods: This was a single-center cross-sectional study conducted between March 2018 and March 2019 at the Department of Blood Purification, Beijing Chao-Yang Hospital, Capital Medical University. One hundred and fifteen HD patients were enrolled. Clinical data on demographics, comorbidities, and the primary cause of end-stage renal disease were obtained by questionnaires. Laboratory data were collected pre- and post-HD. Participants were divided into 3 groups according to PDF degree. Results: The prevalence of PDF in participants was 60% (n = 69); 26.09% had mild PDF; and 33.91% had severe PDF. In the severe PDF group, the prevalence of intradialytic hypotension (IDH) was 38.46%, significantly higher than in the no PDF group (no-PDF; 8.70%) and mild-PDF (16.67%; p = 0.01 for both) groups. In the severe-PDF group, Charlson comorbidity index score and ultrafiltration rate were significantly higher than those in the no-PDF group (p = 0.040, p = 0.020, respectively). In the severe-PDF group, postdialysis lactic acid (Lac) level was significantly higher than that in the no-PDF or mild-PDF groups (p = 0.013 for both). And in the severe-PDF group, postdialysis sodium (Na) was significantly lower than that in the no-PDF or mild-PDF groups (p = 0.026 for both). It was shown by unconditional logistic regression analysis that IDH occurrence (OR 3.821, 95% CI 1.330–10.975), ultrafiltration rates (OR 1.142, 95% CI 1.018–1.281), lower postdialysis Na level (OR 0.724, 95% CI 0.556–0.942), and higher postdialysis Lac level (OR 2.465, 95% CI 1.126–5.397) were associated with PDF (p = 0.013, p = 0.024, p = 0.016, and p = 0.024, respectively). Conclusions: The prevalence of PDF was high among our study participants. PDF incidence was correlated with the IDH occurrence and higher postdialysis Lac and lower postdialysis Na levels. The level of Lac was a significant influencing factor for the fatigue of patients. More attention should thus be paid to PDF.
Intraoperative Ultrasound during Fertility-Sparing Surgery: A Systematic Review and Practical Applications
Authors: Galazis Nicolas , Saso Srdjan , Sorbi Flavia , Jones Benjamin , Landolfo Chiara , Al-Memar Maya , Ben-Nagi Jara , Smith J. Richard , Yazbek Joseph
Published: January 2020

Fertility-sparing surgery (FSS) is an established concept within operative gynaecology. Intraoperative ultrasound (IOUS) has the potential of assessing lesion margins, allowing complete resection with minimal damage to the surrounding healthy tissue and could potentially play a major role in FSS for benign or malignant gynaecological pathologies. In this paper, we review the current literature on the use of IOUS in gynaecological FSS. We also propose technical guidance on the IOUS during FSS. The findings of this review demonstrate that IOUS can assist in the safe resection of disease with high rates of completion, low rates of recurrence and without damage to the nearby healthy reproductive organs. Improved training in transvaginal ultrasonography and minimal access surgery are likely to facilitate the application of IOUS in FSS.
Relationship between Coronary Artery Calcification and Central Chorioretinal Thickness in Patients with Subclinical Atherosclerosis
Authors: Kim Jin Hyung , Kim Seong Eun , Kim Seo Hee , Choi Byoung Wook , Rim Tyler Hyungtaek , Byeon Suk Ho , Kim Sung Soo
Published: January 2020

Purpose: To evaluate the relationship between coronary artery calcification and subfoveal thicknesses of individual chorioretinal layers in subjects with subclinical atherosclerosis by using enhanced-depth imaging optical coherence tomography. Methods: In this retrospective, noninterventional, cross-sectional study, we included 193 eyes from 193 subjects and divided them into three cardiovascular (CV) risk groups based on coronary artery calcification (CAC) scores calculated from cardiac-gated computed tomography: low (CAC = 0; n = 77), intermediate (CAC = 1–300; n = 83), and high (CAC >300; n = 33). Central macula individual retinal layer thicknesses and subfoveal choroidal thickness were measured and compared among groups. Multivariate linear regression was used to evaluate associations of subfoveal choroidal thickness or central retinal thickness with CAC scores. Results: Average subfoveal choroidal thickness differed significantly among low, intermediate, and high CV risk groups (all p < 0.05). There were no statistically significant changes in segmented retinal layer thickness of the central macula. Multivariate regression analyses showed that higher CAC scores were significantly negatively associated with subfoveal choroidal thickness (β = –2.169, p < 0.001). Conclusions: Higher CAC scores were significantly associated with subfoveal choroidal thinning in subjects with subclinical atherosclerosis. Prominent reductions in the subfoveal choroidal layer could provide a useful biomarker for predicting CV risk in patients of advanced age with subclinical atherosclerosis.
iPatrimônio
Authors: Soster Sandra Schmitt , Pratschke Anja
Published: January 2020

De acordo com a Constituição Federal, cabe unir esforços entre Poder Público e comunidade para a promoção e a proteção do patrimônio cultural nacional. Para tanto, é necessário que existam canais de informação e comunicação entre os agentes mencionados. O presente artigo busca mostrar a importância da centralização da informação sobre os bens tombados e registrados pelos vários órgãos de preservação e o papel do georreferenciamento nesse contexto. Por meio de ampla coleta de listas e informações em websites oficiais, foi organizada uma plataforma online chamada iPatrimônio para auxiliar na divulgação do patrimônio cultural brasileiro. Durante a coleta de informações, constatou-se que, quando se trata da divulgação de informação pelos diversos órgãos de preservação: 1. vários órgãos não possuem sites próprios; 2. órgãos que possuem sites próprios nem sempre disponibilizam a lista de bens tombados ou informação sobre eles; e 3. os canais de comunicação com os órgãos não funcionam. Além disso, a plataforma iPatrimônio será analisada em comparação com o INDE e o SICG.
És Tácito ou Plínio? (Plin. Ep. 9.23.3.2)
Authors: Freitas João Victor Lanna de
Published: January 2020

A correspondência de Plínio, o Jovem é uma fonte essencial para compreendermos melhor a sociedade romana durante o governo do imperador Trajano, principalmente as relações sociais entre as aristocracias. Plínio vai se comunicar regularmente com alguns personagens importantes daquela época, inclusive com o próprio imperador. Dentre os aristocratas, o historiador Cornélio Tácito é seu destinatário mais frequente. Neste artigo nos propusemos a analisar a correspondência pliniana à Tácito. Nosso objetivo foi, através dessa documentação, oferecer um cenário mais lúcido quanto à disposição e atuação das elites aristocráticas na política e sociedade romana no início do século II d.C. Para isso, tivemos em conta as estratégias de inserção e consolidação de uma nova aristocracia – provincial e municipal – no centro político do poder – Roma – tendo em vista os lugares sociais ocupados por nossos personagens e as relações estabelecidas entre eles e outros agentes sociais do período.
O Escravismo Estoico de Columella
Authors: Lourenço Helton
Published: January 2020

Este artigo pretende abordar as prescrições sobre a administração e controle do trabalho escravo presentes no pensamento de Columella em seu tratado Sobre as Coisas do Campo (De Re Rustica). Deste modo, nossa hipótese é de que influenciado pela filosofia estoica estas prescrições tem por objetivo estimular a hierarquia dentro do plantel de escravos por meio da competição. Por um lado a competição permite que a distribuição dos cargos e benefícios seja pautada por critérios de capacidade técnica dos escravos, por outro lado acaba por reforçar o poder destes proprietários evitando assim a formação de uma ação conjunta destes trabalhadores contra os interesses dos proprietários e, por conseguinte, por melhores condições de trabalho que não se restringiam apenas promoção individualizada, mas também coletiva.
Slavery and Athens’ Economic Efflorescence
Authors: Porter Jason Douglas
Published: January 2020

Following a recent wave of literature arguing for significant growth in the ancient Greek economy, several ground-breaking books have sought to explain this phenomenon through the lens of New Institutional Economics (NIE). The undeniable prevalence of slavery throughout ancient Greek history, however, has not been substantially integrated into these new analyses. This essay intends to address this problem, by elucidating some of the ways in which slavery contributed to the economic efflorescence of Greece’s late archaic and classical period (600–300 BC) within an institutionally focused approach. Examining specifically the state of Athens, this study contends that not only did the system of slavery import a vast amount of labour from other areas of the Mediterranean into the Athenian polity, but it also directed labour towards economically productive aims that were otherwise  limited by Athens’ societal framework. The use of slaves in milling operations provides a key and often overlooked example, which will here be used as a case study.
"Santa Evita": o cadáver do centro da narrativa
Authors: Clímaco Adriana Ortega
Published: January 2020

O tema do presente artigo é a representação de Evita Perón no romance Santa Evita (1995), de Tomás Eloy Martínez (1934-2010), escritor argentino. Apresenta-se o romance e seu autor, destacando o enredo – a vida de María Eva Duarte de Perón (1919-1952), sua morte, o sequestro e desaparecimento de seu cadáver embalsamado – e sua composição genericamente híbrida. A partir da reflexão de Gajano (2006), Silva (2008), Certeau (2008) e Jolles (1976) sobre o gênero hagiografia, discute-se a representação de Eva Perón realizada no romance. Conclui-se que tal representação é feita de modo hagiográfico, centralizando na narrativa o cadáver embalsamado de Evita.
Sobre el estilo de Unamuno
Authors: Rodríguez John Lionel O´Kuinghttons
Published: January 2020

Este ensayo tiene como objetivo reflexionar sobre el estilo de Miguel de Unamuno, dar algunas características de su prosa e identificar ciertas dificultades con que el traductor de su libro Del sentimiento trágico de la vida puede depararse. Para que dicha reflexión no quede disociada del contenido del libro reviso sucintamente el meollo de las atenciones que atarearon al escritor español en torno al tema de la trascendencia humana.
Frontera Afuera
Authors: Barão Giulia Ribeiro
Published: January 2020

Poema
A doença e a dissolução do sujeito, em Fruta Podrida, de Lina Meruane. O que pode o corpo escrito?
Authors: Francini Ana Carolina Macena
Published: January 2020

O romance contemporâneo Fruta podrida (2008), da escritora chilena Lina Meruane, narra a história de duas irmãs que vivem no campo:  María- a mais velha-, especialista em pesticidas, e Zoila – irmã mais nova-, diagnosticada com diabete. Chama a atenção o fato de a narrativa girar em torno do corpo doente de Zoila o qual, sem estar sob o controle do “sujeito da consciência” da personagem, acaba por ser subjugado pela medicina que, legitimada pelo saber científico, detém o monopólio sobre o corpo enfermo.  Tendo isso em vista, o objetivo deste trabalho é analisar de que modo o romance, ao pôr em foco o corpo doente- seus sofrimentos e suas potencialidades-, problematiza a categoria de ‘pessoa’ ou de ‘sujeito da consciência/de direito’, como única forma possível/reconhecível do ser. A categoria de pessoa pensada para este trabalho é a que está presente em discursos jurídicos, filosóficos e políticos e que sustenta as reivindicações dos direitos humanos, contraditoriamente, tão em voga na contemporaneidade, conforme teorizou o filósofo italiano Roberto Esposito, em seus livros Tercera persona (2009) e Dispositivo de la persona (2011). Dessa forma, será pertinente investigar também como a dissolução da hierarquia binária mente/corpo, no romance de Meruane, pode – como ato político- permear o sensível (RANCIÈRE, 1995), desestabilizar os dispositivos de controle da biopolítica (FOUCAULT, 2004, 2011 ) e instigar por novas formas de liberar e pensar a vida para além da -exclusiva e excludente- categoria de pessoa.
Bypassing the Closest Stroke Center for Thrombectomy Candidates
Authors: Schlemm Ludwig , Endres Matthias , Nolte Christian H.
Published: January 2020

Background and Purpose—

Patients with acute ischemic stroke who have large vessel occlusion benefit from direct transport to a comprehensive stroke center (CSC) capable of endovascular therapy. To avoid harm for patients without large vessel occlusion from delayed access to intravenous thrombolysis (IVT), it has been suggested to only redirect patients with high likelihood of large vessel occlusion for whom the additional delay to intravenous thrombolysis (IVT) caused by transport to the CSC is below a certain threshold. However, which threshold achieves the greatest clinical benefit is unknown.

Methods—

We used mathematical modeling to calculate additional-delay-to-IVT thresholds associated with the greatest reduction in disability-adjusted life years in abstracted 2-stroke center and multiple-stroke center scenarios. Model parameters were extracted from recent meta-analyses or large prospective cohort studies. Uncertainty was quantified in probabilistic and 2-way univariate sensitivity analyses.

Results—

Assuming ideal treatment time performance metrics, transport to the nearest CSC was the preferred strategy irrespective of additional delay-to-IVT when the transfer time between primary stroke center and CSC was <40 minutes (95% credible interval: 25–66 minutes); otherwise, the optimal additional delay-to-IVT-threshold ranged from 28 to 139 minutes. In multiple-stroke center scenarios, optimal additional-delay-to-IVT thresholds were 30 to 54 minutes in urban and 49 to 141 minutes in rural settings; use of optimal thresholds as compared with a 15 minute-threshold saved 0 to 0.11 and 0 to 0.37 disability-adjusted life years per triage case, respectively. Assuming slower treatment times at primary stroke centers and CSCs yielded longer permissible additional delays.

Conclusions—

Our results suggest that patients with acute ischemic stroke with suspected large vessel occlusion should be redirected to a CSC if the additional delay to IVT is <30 minutes in urban and 50 minutes in rural settings.
Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke
Authors: Kunz Wolfgang G. , Almekhlafi Mohammed A. , Menon Bijoy K. , Saver Jeffrey L. , Hunink Myriam G. , Dippel Diederik W.J. , Majoie Charles B.L.M. , Liebeskind David S. , Jovin Tudor G. , Davalos Antoni , Bracard Serge , Guillemin Francis , Campbell Bruce C.V. , Mitchell Peter J. , White Philip , Muir Keith W. , Brown Scott , Demchuk Andrew M. , Hill Michael D. , Goyal Mayank ,   for the HERMES Collaborators
Published: January 2020

Background and Purpose—

The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society.

Methods—

A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy–treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence.

Results—

Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy–treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively.

Conclusions—

Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.