bluuebunny/crossref_metadata_2025 huggingface dataset:
Enterococci and Their Interactions with the Intestinal Microbiome
Authors: Dubin Krista , Pamer Eric G.
Published: November 2017

The
Enterococcus
genus comprises over 50 species that live as commensal bacteria in the gastrointestinal (GI) tracts of insects, birds, reptiles, and mammals. Named “entero” to emphasize their intestinal habitat,
Enterococcus faecalis
and
Enterococcus faecium
were first isolated in the early 1900s and are the most abundant species of this genus found in the human fecal microbiota. In the past 3 decades, enterococci have developed increased resistance to several classes of antibiotics and emerged as a prevalent causative agent of health care-related infections. In U.S. hospitals, antibiotic use has increased the transmission of multidrug-resistant enterococci. Antibiotic treatment depletes broad communities of commensal microbes from the GI tract, allowing resistant enterococci to densely colonize the gut. The reestablishment of a diverse intestinal microbiota is an emerging approach to combat infections caused by antibiotic-resistant bacteria in the GI tract. Because enterococci exist as commensals, modifying the intestinal microbiome to eliminate enterococcal clinical pathogens poses a challenge. To better understand how enterococci exist as both commensals and pathogens, in this article we discuss their clinical importance, antibiotic resistance, diversity in genomic composition and habitats, and interaction with the intestinal microbiome that may be used to prevent clinical infection.
Individualised advance care planning in children with life-limiting conditions
Authors: Loeffen Erik A H , Tissing Wim J E , Schuiling-Otten Meggi A , de Kruiff Chris C , Kremer Leontien C M , Verhagen A A Eduard
Published: November 2017

Introduction

In 2013, the Pediatric Association of the Netherlands launched an evidence-based guideline ‘Palliative care for children’. To promote implementation in daily practice and hereby improve quality of paediatric palliative care, we aimed to develop a functional individualised paediatric palliative care plan (IPPCP) that covers physical, psychological, spiritual and social functioning, with great emphasis on the guideline’s recommendations, advance care planning and patients’ and parents’ preferences and desires.

Methods

A Dutch working group (28 individuals) with a strong multidisciplinary character developed a draft IPPCP, which was piloted retrospectively and prospectively. In the pilots we completed, the IPPCPs for patients who were recently diagnosed with a life-threatening or life-limiting condition and evaluated completeness, usability and user-friendliness.

Results

The final IPPCP comprised five domains: (1) IPPCP data, (2) basics, (3) social, (4) psychosocial and spiritual and (5) physical care. Each domain covered various components. In both pilots, the IPPCP was considered a comprehensive document that covered all areas of paediatric palliative care and was experienced as an improvement to the present situation. However, the current form was regarded to lack user-friendliness.

Conclusion

We propose a set of essential components of a comprehensive IPPCP for paediatric palliative care with extra attention for advance care planning and anticipatory action. Patients’ and parents’ preferences and desires are included next to the recommendations of the evidence-based guideline ‘Palliative care for children’.
Objective cardiovascular assessment in the neonatal intensive care unit
Authors: Dempsey Eugene M , El-Khuffash Afif Faisal
Published: November 2017

Traditionally, cardiovascular well-being was essentially based on whether the mean blood pressure was above or below a certain value. However, this singular crude method of assessment provides limited insight into overall cardiovascular well-being. Echocardiography has become increasingly used and incorporated into clinical care. New objective modality assessments of cardiovascular status continue to evolve and are being evaluated and incorporated into clinical care. In this review article, we will discuss some of the recent advances in objective assessment of cardiovascular well-being, including the concept of multimodal monitoring. Sophisticated haemodynamic monitoring systems are being developed, including mechanisms of data acquisition and analysis. Their incorporation into clinical care represents an exciting next stage in the management of the infant with cardiovascular compromise.
Nephrotic syndrome and acute kidney injury induced by malathion toxicity
Authors: Yokota Kei , Fukuda Masamichi , Katafuchi Ritsuko , Okamoto Tadashi
Published: November 2017

We treated a case of acute kidney injury and nephrotic syndrome after malathion inhalation. A 69-year-old Japanese man presented with oedema 15 days after inhalation of malathion, a widely used pesticide. Serum albumin was 2.4 g/dL, urinary protein 8.6 g/gCr and serum creatinine 2.5 mg/dL. Kidney biopsy revealed tubular cell damage, epithelial cell damage in glomeruli and diffuse foot process effacement in electron microscopy. Acute kidney injury progressed to treatment with dialysis. Renal function recovered after corticosteroid administration from the 43rd day after admission. Malathion inhalation should be ruled out as a differential diagnosis in individuals who develop acute kidney injury and nephrotic syndrome, especially in rural-dwelling patients.
Radiation retinopathy treated successfully with aflibercept
Authors: Pooprasert Pakinee , Young-Zvandasara Tafadzwa , Al-bermani Ayad
Published: November 2017

Aflibercept (aflibercept) is a novel anti-vascular endothelial growth factor drug indicated for wet age-related macular degeneration and macular oedema secondary to retinal vein occlusion and diabetic macular oedema. While only newly introduced on the market, it is growing in popularity and over 5.5 million doses have been prescribed worldwide. Due to its versatile mechanism, it is indicated for numerous eye pathologies, and in particular, has been adapted to treat various types of retinopathy. To our knowledge, this is the first case report of solely using aflibercept to treat cystoid macular oedema in radiation retinopathy.
Effect of regular exercise training on changes in HbA1c, BMI and VO2max among patients with type 2 diabetes mellitus: an 8-year trial
Authors: Najafipour Farzad , Mobasseri Majid , Yavari Abbas , Nadrian Haidar , Aliasgarzadeh Akbar , Mashinchi Abbasi Naimeh , Niafar Mitra , Houshyar Gharamaleki Jalil , Sadra Vahideh
Published: November 2017

Objective

The effects of regular exercise on the health promotion of patients with type 2 diabetes mellitus (T2DM) have been well documented. The present study investigated the long-term effects of regular exercise training on biological indicators among these patients.

Methods

In this quasi-experimental trial with pretest-post-test design, 65 patients with T2DM aged 33–69 years (experiment (35), control (30)) participated. After 8 years of conducting the program, the data on 30 patients (experiment (15), control (15)) were entered into analysis. The training program included aerobic exercise three sessions per week, 90 min, 50%–80% VO2max. Before and after the intervention, the biological indicators (hemoglobin A1c (HbA1c), body mass index (BMI) and VO2max) were measured. Data were analyzed using multivariate analysis of covariance.

Results

Our long-term exercise training program had a significant effect on HbA1C, BMI and Vo2max (P<0.05). Compared with patients in the control group, HbA1c was significantly reduced and BMI and VO2max were significantly improved among the experiment group.

Conclusions

Long-term regular physical activity training was found to be helpful in improving glycemic control, body composition and cardiovascular fitness among patients with T2DM. Long-term continuous physical activity offsets the deteriorations of biological indicators found in the control group. Further research, with a particular focus on practical and real-world programming, is needed to determine the responsive health outcomes of such long-term programs on the patients.
Exploring the characteristics of the high-cost population from the family perspective: a cross-sectional study in Jiangsu Province, China
Authors: Miao Yudong , Qian Dongfu , Sandeep Sandeep , Ye Ting , Niu Yadong , Hu Dan , Zhang Liang
Published: November 2017

Background

Across a range of healthcare settings, 5% of the population accounts for half of healthcare spending: these patients are identified as a ‘high-cost population’. Characterising high-cost users is essential for predicting potential high-cost patients and the development of appropriate interventions to improve the management and financing of these patients.

Objective

This cross-sectional study aimed to explore the characteristics of this high-cost population from a family perspective in China and provide suggestions for social health insurance policy development.

Methods

This study used data from the Fifth Health Service Investigation of Jiangsu Province (2013), and 12 600 families were enrolled for analysis. Households whose medical expenditures were among the top 5% were identified to be high-cost families. A t-test, a Χ2test, and a binary logistic regression were used.

Results

High-cost families (n=631, 5%) accounted for 44.9% of the total medical expenditure of sampled families. High-cost families had 3.2 members and 1.2 chronic disease patients per household, which is significantly more than the 2.9 members and 0.7 people in the remaining families, respectively (p<0.05). Bi-weekly emergency department visits and annual hospitalisations preceding the household investigation of high-cost families were 1.19 and 0.98 per household, which is significantly more than the 0.68 and 0.17 of the remaining families, respectively (p<0.05). A binary logistic regression indicated that the number of family members (OR 1.152), the number of chronic disease patients (OR 1.508), bi-weekly emergency department visits (OR 1.218), and annual hospitalisations (OR 4.577) were associated with high costs.

Conclusion

The 5% high-cost families in Jiangsu Province accounted for approximately half of medical expenditures. The effectiveness of Chinese Social Health Insurance in lowering high-cost families’ risk of catastrophic health expenditure was modest. Policymakers need to ascertain the priority of lowering the burden of high-cost families’ out-of-pocket expenses through improving the reimbursement proportion and reducing avoidable medical services.
London Transfer Project: improving handover documentation from long-term care homes to hospital emergency departments
Authors: Carson Joseph , Gottheil Stephanie , Gob Alan , Lawson Sherri
Published: November 2017

About one-quarter of all long-term care (LTC) residents are transferred to an emergency department (ED) every 6 months in Ontario, Canada. When residents are unable to describe their health issues, ED staff rely on LTC transfer reports to make informed decisions. However, transfer information gaps are common, and may contribute to unnecessary tests, unwanted treatments and longer ED length of stay. London Health Sciences Centre, an academic hospital system in London, Ontario, partnered with 10 LTC homes to improve emergency reporting of their residents' reason for transfer and baseline cognition. After conducting a root cause analysis, 7 of 10 homes implemented a standard minimum set of currently available transfer forms, including a computer-generated summary of resident’s most recent interRAI functional assessment. Results were analysed using statistical process control charts and data were posted on a public website (LondonTransferProject.com). The documentation rate of ‘reason for transfer’ improved from 61% to 84%, and ‘baseline cognitive status’ improved from 4% to 56% across all 10 homes. These results suggest that transfer communication can be improved by codesigning and implementing solutions with ED and LTC staff, which build upon current reporting practices shared across multiple LTC organisations.
Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2
Authors: Seyerle Amanda A , Lin Henry J , Gogarten Stephanie M , Stilp Adrienne , Méndez Giráldez Raul , Soliman Elsayed , Baldassari Antoine , Graff Mariaelisa , Heckbert Susan , Kerr Kathleen F , Kooperberg Charles , Rodriguez Carlos , Guo Xiuqing , Yao Jie , Sotoodehnia Nona , Taylor Kent D , Whitsel Eric A , Rotter Jerome I , Laurie Cathy C , Avery Christy L
Published: November 2017

Objective

PR interval (PR) is a heritable electrocardiographic measure of atrial and atrioventricular nodal conduction. Changes in PR duration may be associated with atrial fibrillation, heart failure and all-cause mortality. Hispanic/Latino populations have high burdens of cardiovascular morbidity and mortality, are highly admixed and represent exceptional opportunities for novel locus identification. However, they remain chronically understudied. We present the first genome-wide association study (GWAS) of PR in 14 756 participants of Hispanic/Latino ancestry from three studies.

Methods

Study-specific summary results of the association between 1000 Genomes Phase 1 imputed single-nucleotide polymorphisms (SNPs) and PR assumed an additive genetic model and were adjusted for global ancestry, study centre/region and clinical covariates. Results were combined using fixed-effects, inverse variance weighted meta-analysis. Sequential conditional analyses were used to identify independent signals. Replication of novel loci was performed in populations of Asian, African and European descent. ENCODE and RoadMap data were used to annotate results.

Results

We identified a novel genome-wide association (P<5×10−8) with PR at ID2 (rs6730558), which replicated in Asian and European populations (P<0.017). Additionally, we generalised 10 previously identified PR loci to Hispanics/Latinos. Bioinformatics annotation provided evidence for regulatory function in cardiac tissue. Further, for six loci that generalised, the Hispanic/Latino index SNP was genome-wide significant and identical to (or in high linkage disequilibrium with) the previously identified GWAS lead SNP.

Conclusions

Our results suggest that genetic determinants of PR are consistent across race/ethnicity, but extending studies to admixed populations can identify novel associations, underscoring the importance of conducting genetic studies in diverse populations.
Can reference images improve interobserver agreement in reporting liver fibrosis?
Authors: German Alyn L , Fleming Kenneth , Kaye Philip , Davies Susan , Goldin Robert , Hubscher Stefan G , Tiniakos Dina , McGregor Angus , Wyatt Judith I
Published: November 2017

Staging of fibrosis in medical liver biopsies has inherent interobserver variability. There are a number of disease-specific scoring systems available. While recognising the importance of these scoring systems, there is scope to consider how concordance amongst histopathologists could be improved using a generic fibrosis staging system.

Using virtual slides, we approached both specialist liver histopathologists and general histopathologists from the UK to assess the degree of fibrosis against a proposed four-tiered reporting system. Example reference images were then produced and distributed to the same responders who were asked to rate a second set of slides to assess if the use of reference images improved concordance between pathologists.

The use of reference images eliminated spread across three categories (from 15% to 0%). Overall, agreement was already good; our study showed an improved agreement amongst all participants for percentage agreement (67.79% to 70.08%) and interobserver agreement improved (Fleiss’ Kappa 0.55 to 0.59).
Homozygous mutation inCEP19,a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly
Authors: Yıldız Bölükbaşı Esra , Mumtaz Sara , Afzal Muhammad , Woehlbier Ute , Malik Sajid , Tolun Aslıhan
Published: November 2017

Background

Bardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype.

Methods

SNP genotype data were used for linkage analysis and exome sequencing to identify mutations. Modelling and in silico analysis were performed to predict mutation severity.

Results

Patients had postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver. The 4.57 Mb disease locus harboured homozygous, truncatingCEP19c.194_195insA (p.Tyr65*) mutation. We also foundglioma-associated oncogene homolog1(GLI1) c.820G>C (p.Gly274Arg) in the homozygous state in most patients. In silico modelling strongly suggests that it is damaging. Also, different combinations of four possible modifier alleles in BBS-related genes were detected. Two are known modifier alleles for BBS, splicing variantCCDC28Bc.330C>T and missenseMKKS/BBS6p.Ile339Val, and the others areC8ORF37/BBS21p.Ala178Val andTMEM67/BBS14 modifierp.Asp799Asp. Some patients carry all those five known/possible modifier alleles. Such variants are highly significantly more abundant in our patients than in a control group.

Conclusion

CEP19encodes a centrosomal and ciliary protein, as all BBS genes do. Another truncating mutation p.Arg82* has been reported as responsible for morbid obesity in a family; however, in the family we present, not all homozygotes are obese, although some are severely obese. The variant inGLI1, encoding a transcription factor that localises to the primary cilium and nucleus and is a mediator of the sonic hedgehog pathway, possibly exacerbates disease severity when in the homozygous state.
What is your client thinking and why should you care?
Authors: Belshaw Zoe
Published: November 2017

Zoe Belshaw is coordinating our new series that gives an insight into what clients’ experiences are and how you can help them. Here, she outlines how the series came into being
A pilot study investigating reactive oxygen species production in capillary blood after a marathon and the influence of an antioxidant-rich beetroot juice
Authors: Clifford Tom , Bowman Amy , Capper Tess , Allerton Dean M. , Foster Emma , Birch-Machin Mark , Lietz Georg , Howatson Glyn , Stevenson Emma J.
Published: November 2017

We report that reactive oxygen species (ROS), as measured in capillary blood taken from the finger-tip, increased after a marathon (+128% P < 0.01; effect size = 1.17), indicating that this collection method might be useful for measuring ROS in field settings. However, mitochondrial DNA damage remained unchanged. Beetroot juice, taken before and after exercise, was unable to mitigate exercise-induced ROS production, questioning its use an antioxidant-rich food.
Catalytic asymmetric Friedel–Crafts synthesis of 1,1′-diaryl-2-substituted 4-pentenes enables stereoselective access to functionalized tetrahydronaphthalenes
Authors: Chénard Étienne , Cusson Jean-Philippe , Hanessian Stephen
Published: November 2017

A series of electron-rich arenes were reacted with 1-alkyl or 1-aryl 1′-allyl benzylic alcohols to give the corresponding 1,1′-diarylalkanes, in the presence of Lewis and Brønsted acids as catalysts. In the presence of HBF4, 1,1′-diarylalkanes containing an allylic chain were shown to form tetrahydronaphthalenes through a rearrangement involving spirocyclic intermediates. The mechanism of the cyclization is discussed.
Core-polarization corrected relativistic energies and radiative data for one-electron spectra of Bi V through U XIV
Authors: Migdalek J.
Published: November 2017

The relativistic core-polarization corrected Dirac–Fock energy levels, oscillator strength, and lifetimes are predicted for highly ionized spectra of gold isoelectronic sequence from Bi V through U XIV. It is demonstrated that core polarization (core–valence electron correlation) strongly affects oscillator strengths and lifetimes of 6s–6p, 6p–5d, and 6d–5f transitions (the latter particularly in the vicinity of the collapse region) even for highly ionized systems of gold isoelectronic sequence.
Stability in quadratic torsion theories
Authors: Vasilev Teodor Borislavov , Cembranos Jose A. R. , Valcarcel Jorge Gigante , Martín-Moruno Prado
Published: November 2017

We revisit the definition and some of the characteristics of quadratic theories of gravity with torsion. We start from a Lagrangian density quadratic in the curvature and torsion tensors. By assuming that General Relativity should be recovered when the torsion vanishes and investigating the behaviour of the vector and pseudo-vector torsion fields in the weak-gravity regime, we present a set of necessary conditions for the stability of these theories. Moreover, we explicitly obtain the gravitational field equations using the Palatini variational principle with the metricity condition implemented via a Lagrange multiplier.
Usefulness of Chinese Herbal Medicines as Host-Directed Therapeutics against Mycobacterial Infections: A Review
Authors: Tomioka Haruaki
Published: November 2017

The high incidence of tuberculosis (TB) in developing countries, the resurgence of TB in industrialized countries, and the worldwide increase in the prevalence of Mycobacterium avium complex infections have prompted the quest for new antimycobacterial drugs. However, the development of such chemotherapeutics is currently making very slow progress. It therefore appears that devising improved administration protocols for clinical treatment against intractable mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of novel antimycobacterial drugs. The modulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. Particularly, the mild and long-term up-regulation of host immune reactions against mycobacterial pathogens using Chinese herbal medicines (CHMs) may be beneficial for immunoadjunctive therapy. This review focuses on the current status and future prospects regarding the development of CHMs that can be useful for the clinical control of intractable mycobacterial infections.
Melaleuca alternifolia Induces Heme Oxygenase-1 Expression in Murine RAW264.7 Cells through Activation of the Nrf2-ARE Pathway
Authors: Lee Shih-Yu , Chen Po-Yu , Lin Jung-Chun , Kirkby Nicholas S. , Ou Ching-Huei , Chang Tsu-Chung
Published: November 2017

Melaleuca alternifolia concentrate (MAC) is the refined essential oil of the Australian native plant Melaleuca alternifolia. MAC has been reported to suppress the production of pro-inflammatory cytokines in both murine RAW264.7 macrophages and human monocytes stimulated with lipopolysaccharide (LPS). However, the mechanisms involved in this effect remain unclear. This study aims to delineate the molecular mechanisms that drive the anti-inflammatory activity of MAC and its active component, terpinen-4-ol, in macrophages. The effects of MAC on RAW264.7 cells were studied using western blotting, real-time PCR, an electrophoretic mobility shift assay (EMSA), and NF-[Formula: see text]B luciferase reporter assays. Our results showed that MAC significantly increased both the mRNA and protein levels of heme oxygenase-1 (HO-1) via p38 and JNK MAPK activation. In addition, we showed that MAC significantly increased the activation and nuclear translocation of NF-E2-related factor 2 (Nrf2), a key transcription factor regulating HO-1 induction. MAC was also associated with significant inhibition of iNOS expression, NO production, and NF-[Formula: see text]B activation. HO-1 was required for these anti-inflammatory effects as tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the effects of MAC on LPS-induced iNOS, NO, and NF-[Formula: see text]B activation. Our results indicate that MAC induces HO-1 expression in murine macrophages via the p38 MAPK and JNK pathways and that this induction is required for its anti-inflammatory activity.
Carnosol-Induced ROS Inhibits Cell Viability of Human Osteosarcoma by Apoptosis and Autophagy
Authors: Lo Yu-Cheng , Lin Yung-Chi , Huang Yi-Fu , Hsieh Chen-Pu , Wu Chia-Chieh , Chang Ing-Lin , Chen Chiu-Liang , Cheng Chun-Hsiang , Chen Hsin-Yao
Published: November 2017

Carnosol is an anti-oxidant and anti-inflammatory compound from rosemary. In this paper, we investigated antitumor activity of carnosol against human osteosarcoma cells. We found the viability of human osteosarcoma MG-63 cells was significantly decreased in the presence of carnosol (cell viabilities: 17.2% for 20[Formula: see text]μg/ml of CS vs. 100% for control, [Formula: see text]). Carnosol induced apoptosis and cell cycle arrest in a dose-dependent manner in MG-63 cells. Furthermore, carnosol exposure increased the levels of reactive oxygen species (ROS). The pre-treatment of NAC, the ROS scavenger, blocked the inhibition of cell viability in the carnosol treatment, indicating that ROS is important in the antiproliferation effect. Moreover, we demonstrated that carnosol significantly induced autophagy and co-administration of autophagy inhibitor reduced the antiproliferating effect of carnosol. This result exhibited the cytotoxic effect of autophagy induced by carnosol in MG-63 cells. Interestingly, the treatment of NAC decreased carnosol-induced autophagy. Collectively, these data indicate that carnosol suppresses the viability of human osteosarcoma MG-63 cells by upregulation of apoptosis and autophagy, which are both mediated by ROS. Thus, carnosol might serve as a potential therapeutic agent against osteosarcoma.
Prostate Cancer Xenograft Inhibitory Activity and Pharmacokinetics of Decursinol, a Metabolite of Angelica gigas Pyranocoumarins, in Mouse Models
Authors: Wu Wei , Tang Su-Ni , Zhang Yong , Puppala Manohar , Cooper Timothy K. , Xing Chengguo , Jiang Cheng , Lü Junxuan
Published: November 2017

We have previously shown that the ethanol extract of dried Angelica gigas Nakai (AGN) root exerts anticancer activity against androgen receptor (AR)-negative human DU145 and PC-3 prostate cancer xenografts and primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The major pyranocoumarin isomers decursin (D) and decursinol angelate (DA), when provided at equi-molar intake to that provided by AGN extract, accounted for the inhibitory efficacy against precancerous epithelial lesions in TRAMP mice. Since we and others have shown in rodents and humans that D and DA rapidly and extensively convert to decursinol, here we tested whether decursinol might be an in vivo active compound for suppressing xenograft growth of human prostate cancer cells expressing AR. In SCID-NSG mice carrying subcutaneously inoculated human LNCaP/AR-Luc cells overexpressing the wild type AR, we compared the efficacy of 4.5[Formula: see text]mg decursinol per mouse with equi-molar dose of 6[Formula: see text]mg D/DA per mouse. The result showed that decursinol decreased xenograft tumor growth by 75% and the lung metastasis, whereas D/DA exerted a much less effect. Measurement of plasma decursinol concentration, at 3[Formula: see text]h after the last dose of respective dosing regimen, showed higher circulating level in the decursinol-treated NSG mice than in the D/DA-treated mice. In a subsequent single-dose pharmacokinetic experiment, decursinol dosing led to 3.7-fold area under curve (AUC) of plasma decursinol over that achieved by equi-molar D/DA dosing. PK advantage notwithstanding, decursinol represents an active compound to exert in vivo prostate cancer growth and metastasis inhibitory activity in the preclinical model.
Quenching and room-temperature annealing effects on the conductivity of underdoped HoBa2Cu3O7−δ
Authors: Khadzhai G. Ya. , Vovk R. V. , Vovk N. R. , Boiko Yu. I. , Kamchatnaya S. N. , Pinto Simoes V. M. , Dobrovolskiy O. V.
Published: November 2017

The effects of quenching from 600[Formula: see text]C and subsequent room-temperature annealing on the basal-plane electrical resistivity of underdoped HoBa2Cu3O[Formula: see text] single crystals are investigated. Regions with different superconducting transition temperatures, [Formula: see text], have been revealed in the sample after quenching and attributed to a non-uniform distribution of the labile oxygen in the sample volume. Room-temperature annealing has been revealed to lead to an increase of [Formula: see text] of all regions and a decrease of their number, attributed to the coalescence of clusters of oxygen vacancies. The temperature dependence of the resistance in the normal state is characterized by a decrease of the residual resistivity and the phonon scattering coefficient.
BDSDE with Poisson jumps under stochastic Lipschitz and linear growth conditions
Authors: Sow Ahmadou Bamba , Sagna Yaya
Published: November 2017

In this paper, we deal with a backward doubly stochastic differential equations with jumps. Under stochastic Lipschitz conditions on the coefficients, we prove the existence and uniqueness of solution and provide a comparison theorem. Using this comparison theorem, we show the existence of a minimal solution when the drift satisfy a stochastic growth condition.
A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion
Authors: Avruch James H. , Bruinsma Bote G. , Weeder Pepijn D. , Sridharan Gautham V. , Porte Robert J. , Yeh Heidi , Markmann James F. , Uygun Korkut
Published: November 2017

Machine perfusion-based organ preservation techniques are prudently transitioning into clinical practice. Although experimental data is compelling, the outcomes in the highly variable clinical donation-transplantation setting are unpredictable. Here, we offer an intermediate tool for pre-clinical assessment of human donor livers. We present a model for ex situ reperfusion of discarded human livers and report on its application in three human livers that have undergone subnormothermic (21[Formula: see text]C) machine perfusion as an experimental preservation method. During reperfusion, the livers macroscopically reperfused in the first 15 minutes, and remained visually well-perfused for 3 hours of ex situ reperfusion. Bile production and oxygen consumption were observed throughout ex situ reperfusion. ATP levels increased 4.25-fold during SNMP. Between the end of SNMP and the end of reperfusion ATP levels dropped 45%. ALT levels in blood increased rapidly in the first 30 minutes and ALT release continued to taper off towards the end of perfusion. Release of CRP, TNF-[Formula: see text], IL-1[Formula: see text], and IL-12, IFN-[Formula: see text] was sustained during reperfusion. These findings support the use of this model for the evaluation of novel human liver preservation techniques.
Geology and hydrocarbon potential of offshore SE Somalia
Authors: Davidson L. M. , Arthur T. J. , Smith G. F. , Tubb S.
Published: November 2017

Interpretation of a 20 550 line km 2D seismic survey acquired in 2014 by Soma Oil and Gas in the deep water offshore area of SE Somalia has identified three previously undocumented sedimentary provinces – Jubba Deep, Mogadishu Deep and Mid Somalia High – all of which have distinctive geological characteristics. Well and stratigraphic controls are limited, with inferred lithologies largely based on seismic stratigraphic interpretation.

The Jubba Deep has a thick Late Cretaceous–Early Tertiary deltaic section deformed by major gravitational collapses in the Paleocene-age Kismaayo Thrust Belt (KTB) and the Pliocene-age Baraawe Thrust Belt (BTB). It is proposed that the KTB has significant hydrocarbon potential in deltaic and pro-delta sands trapped in thrust anticlines and sourced with oil from Mid-Cretaceous mobile shales.

The Mogadishu Deep Basin has a thick Mesozoic and Tertiary section but is missing the thick deltaics seen in the Jubba Basin. Volcanics are present in this basin.

The Mid Somalia High has a relatively thinner sedimentary section where Cretaceous and Jurassic reservoirs and potential source rocks are at moderate burial depths. An extensive post-rift Mid–Late Jurassic carbonate platform is developed here with potential hydrocarbon targets in interpreted reefs and shoal facies.

Supplementary material
: Additional seismic examples and map figures are available at
https://doi.org/10.6084/m9.figshare.c.3902650
SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux
Authors: Shen Wen-Jun , Azhar Salman , Kraemer Fredric B.
Published: November 2017

The scavenger receptor, class B type 1 (SR-B1), is a multiligand membrane receptor protein that functions as a physiologically relevant high-density lipoprotein (HDL) receptor whose primary role is to mediate selective uptake or influx of HDL-derived cholesteryl esters into cells and tissues. SR-B1 also facilitates the efflux of cholesterol from peripheral tissues, including macrophages, back to liver. As a regulator of plasma membrane cholesterol content, SR-B1 promotes the uptake of lipid soluble vitamins as well as viral entry into host cells. These collective functions of SR-B1 ultimately affect programmed cell death, female fertility, platelet function, vasculature inflammation, and diet-induced atherosclerosis and myocardial infarction. SR-B1 has also been identified as a potential marker for cancer diagnosis and prognosis. Finally, the SR-B1–linked selective HDL-cholesteryl ester uptake pathway is now being evaluated as a gateway for the delivery of therapeutic and diagnostic agents. In this review, we focus on the regulation and functional significance of SR-B1 in mediating cholesterol movement into and out of cells.
Therapeutic potential of microRNAs for the treatment of renal fibrosis and CKD
Authors: Lv Wenshan , Fan Fan , Wang Yangang , Gonzalez-Fernandez Ezekiel , Wang Chen , Yang Lili , Booz George W. , Roman Richard J.
Published: November 2017

Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD. MicroRNAs (miRNAs) are small noncoding RNA molecules, 18–22 nucleotides in length, that control many developmental and cellular processes as posttranscriptional regulators of gene expression. Emerging evidence suggests that miRNAs targeted against genes involved in renal fibrosis might be potential candidates for the development of antifibrotic therapies for CKD. This review will discuss some of the miRNAs, such as Let-7, miR-21,-29, -192, -200,-324, -132, -212, -30, -126, -433, -214, and -199a, that are implicated in renal fibrosis and the potential to exploit these molecular targets for the treatment of CKD.
A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy
Authors: Jungmann Sven , Ludwig Wolf-Dieter , Schönfeld Nicolas , Blum Torsten-Gerriet , Großwendt Claudia , Boch Christian , Rehbock Beate , Griff Sergej , Schmittel Alexander , Bauer Torsten T.
Published: November 2017

We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.
Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer
Authors: Janjigian Yelena Y. , Sanchez-Vega Francisco , Jonsson Philip , Chatila Walid K. , Hechtman Jaclyn F. , Ku Geoffrey Y. , Riches Jamie C. , Tuvy Yaelle , Kundra Ritika , Bouvier Nancy , Vakiani Efsevia , Gao Jianjiong , Heins Zachary J. , Gross Benjamin E. , Kelsen David P. , Zhang Liying , Strong Vivian E. , Schattner Mark , Gerdes Hans , Coit Daniel G. , Bains Manjit , Stadler Zsofia K. , Rusch Valerie W. , Jones David R. , Molena Daniela , Shia Jinru , Robson Mark E. , Capanu Marinela , Middha Sumit , Zehir Ahmet , Hyman David M. , Scaltriti Maurizio , Ladanyi Marc , Rosen Neal , Ilson David H. , Berger Michael F. , Tang Laura , Taylor Barry S. , Solit David B. , Schultz Nikolaus
Published: November 2017

The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability–high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein–Barr virus–positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance.

Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49–58. ©2017 AACR.

See related commentary by Sundar and Tan, p. 14.

See related article by Pectasides et al., p. 37.

This article is highlighted in the In This Issue feature, p. 1
Soluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytes
Authors: Horn Lucas A. , Long Tiha M. , Atkinson Ryan , Clements Virginia , Ostrand-Rosenberg Suzanne
Published: November 2017

Tumor cells use various immune-suppressive strategies to overcome antitumor immunity. One such method is tumor expression of programmed death ligand-1 (PD-L1), which triggers apoptotic death or anergy upon binding programmed death-1 (PD-1) on T cells. Our previous in vitro cellular studies with human and mouse PD-L1+ tumor cells demonstrated that a soluble form of the costimulatory molecule CD80 prevented PD-L1–mediated immune suppression and restored T-cell activation by binding PD-L1 and blocking interaction with PD-1. We now report that in vivo treatment of established syngeneic PD-L1+ CT26 colon carcinoma and B16F10 melanoma tumors with CD80-Fc delays tumor growth and promotes tumor-infiltrating T cells. Studies with PD-1−/− and CD28−/− mice demonstrate that soluble CD80 acts in vivo by simultaneously neutralizing PD-1 suppression and activating through CD28. We also report that soluble CD80 mediates its effects by activating transcription factors EGR1-4, NF-κB, and MAPK, downstream signaling components of the CD28 and T-cell receptor pathways. Soluble CD80 binds to CTLA-4 on activated human peripheral blood mononuclear cells. However, increasing quantities of CTLA-4 antagonist antibodies do not increase T-cell activation. These results indicate that soluble CD80 does not suppress T-cell function through CTLA-4 and suggest that CTLA-4 acts as a decoy receptor for CD80, rather than functioning as a suppressive signaling receptor. Collectively, these studies demonstrate that soluble CD80 has therapeutic efficacy in vivo in mouse tumor systems and that its effects are due to its ability to inhibit PD-1–mediated suppression while concurrently activating T cells through CD28. Cancer Immunol Res; 6(1); 59–68. ©2017 AACR.
MRI Signal Abnormalities of the Inferior Olivary Nuclei in Spinocerebellar Ataxia Type 2
Authors: Yoshii Fumihito , Tomiyasu Hitoshi , Watanabe Ryo , Ryo Masafuchi
Published: November 2017

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant spinocerebellar degeneration, associated with extended repeats of the trinucleotide CAG in the ATXN2 gene on the long arm of chromosome 12. Magnetic resonance imaging (MRI) of SCA2 showed significant atrophies of the brainstem, middle cerebellar peduncles, and cerebellum. We report two genetically proven SCA2 patients who showed hypertrophy of the inferior olivary nuclei on proton density- and T2-weighted MRI. This pattern has never been reported in patients with SCA1, SCA3, or SCA6, and may make it possible to differentiate SCA2 from other hereditary spinocerebellar ataxias.
Intracranial Epidural Haematoma following Surgical Removal of a Giant Lumbosacral Schwannoma: A Case Report and Literature Review
Authors: Nemir Jakob , Peterković Vjerislav , Trninić Ines , Domazet Ivan , Barić Hrvoje , Vukić Miroslav
Published: November 2017

Postoperative intracranial epidural haematoma (EDH) is an extremely rare complication following spinal surgery, with only a handful of cases described in the literature. We report the case of a 16-year-old girl who underwent a successful subtotal resection of a giant lumbosacral schwannoma (L2-S2 level). Recovery from general anaesthesia was uneventful; however, her neurological status deteriorated rapidly within 24 h after surgery. A head computed tomography scan revealed a large right frontoparietal EDH with midline shift. An immediate frontotemporoparietal osteoplastic craniotomy and evacuation of the EDH were performed. At 1 year postoperatively, the patient regained full neurological recovery with no radiological signs of growth of the residual tumour.
Ультраструктурний стан пародонта при удосконаленні клаптевої операції у лікуванні хворих на генералізований пародонтит
Authors: Ohiienko S. A. , Piuryk V. P. , Popadynets O. H.
Published: November 2017

Among all surgical dental diseases periodontal disease occupies one of the leading places, taking into account the prevalence of this pathology among the population and its negative consequences (loss of teeth and impaired functions of the tooth-jaw system). The severity of GP, frequent relapses and complications leads to a decrease in the quality of life of patients, signifi cant socio-economic losses, impaired chewing and speech.The aim of the study – to increase the effectiveness of surgical treatment of patients with GP III degree of severity by improving certain technological steps in the operations of Tseshynskyi-Widman-Neimann.Materials and Methods. We operated 46 patients with chronic generalized paradontitis (GP) of the III degree, divided into two groups: group I (20 people), which was the traditional modifi ed operation of Tseshynskyi-Vidman-Neimann; Patients of the group II (26 persons) – modifi ed operation of Teshynskyi-Vidman-Neimann, improved by the method of periost penetration with medical correction (using oral trays with miramistin and applications of methyluracil ointment with miramistin on periodontal tissues and postoperative sutures with application in the postoperative periods of the preparation “Glutargin “(First in injections No. 5 intravenous 5 ml (2 g) per 200 ml of 0.9 % sodium chloride solution 2 times a day and then in tablets – 4 tablets of 0.75 mg 3 times a day for a month).Results and Discussion. After the treatment, it was found that the average rate of the Schiller-Pysariev sample was higher in patients of group I (2.5 ± 0.05%) compared with the corresponding index of group II (0.95±0.04 %). After treatment, the average index of bleeding index was (0.77±0.04) points in the group I and (0.32±0.04) points in the group II. The ultrastructural state of periodontal undergoes positive transformations in shorter terms in patients of the group II. Thus, the use of peristaltic penetration with medical correction in the surgical treatment of patients with a GP of the III degree has advantages over traditional treatment.Conclusions. As a result of the research, the technological chain of the modifi ed Tseshynskyi-Vidman-Neimann operation was improved for the treatment of GP patients with a chronic course of the third degree through periosteal penetration. Ultrastructurally up to the twelfth month after operative intervention in the periodontitis of patients of the fi rst and second groups, a positive dynamics is observed; however, better morphological transformations occur in the periodontitis of patients who underwent periosteal penetration in combination with drug correction.