bluuebunny/crossref_metadata_2025 huggingface dataset:
High occurrence of small intestinal bacterial overgrowth in primary biliary cholangitis
Authors: Liu Chen Kiow Jeremy , Vincent Catherine , Sidani Sacha , Bouin Mickael
Published: August 2019

Background

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease affecting mainly middle‐aged women. An alteration in intestinal motility has been well documented in cirrhosis predisposing to small intestinal bacterial overgrowth (SIBO). Patients with PBC frequently complain of various gastrointestinal symptoms compatible with SIBO. No study has specifically been published to this day to determine the occurrence of SIBO in PBC. Our objective was to determine the prevalence of SIBO in patients with PBC.

Methods

Retrospective study from 2010 to 2018. All patients diagnosed with PBC during this period had a systematic screening for SIBO in their diagnostic workup. The diagnosis of SIBO was made by a carbohydrate breath test (lactulose and/or glucose). Clinical and paraclinical factors of patients were compared with a control group of healthy subjects.

Key Results

Ninety‐eight subjects were included in the study (mean age 49, range 21‐88 years) including 58 patients with PBC and 40 healthy subjects. The PBC group was older than the control group (mean age 56, range 31‐88 vs 39, range 21‐62 years; P < .001), but identical for gender and body mass index. The prevalence of SIBO was higher in PBC versus controls (32.8% vs 2.5%; P < .001). The PBC group with SIBO had significantly more diarrhea (78.9% vs 35.9%; P < .05) than the PBC group without SIBO, but the prevalence of abdominal pain and bloating was similar.

Conclusions & Inferences

The high occurrence of SIBO in PBC may explain some of the frequently reported gastrointestinal symptoms. This study justifies the systematic screening for SIBO in PBC.
Intrafollicular and systemic serotonin, oestradiol and progesterone concentrations in cycling mares
Authors: Satué Katiuska , Fazio Esterina , Ferlazzo Adriana , Medica Pietro
Published: August 2019

The hypothesis that a local serotonergic network might also exist in the follicle of mares remains poorly documented, with exception for humans and laboratory species. For this reason, the aim of the present study was to clarify this possibility, investigating intrafollicular serotonin concentrations of the cycling mare at ovulation time. Sixty ovaries collected from 30 clinically healthy mares of slaughterhouse meat production with clinically normal reproductive tracts after slaughtering were evaluated. Blood samples were taken prior to sacrifice. Follicles were classified in three categories in relation to size, as small (20–30 mm), medium (31–40 mm) and large (>41 mm), and the follicular fluid samples were extracted from each follicle. Intrafollicular and systemic serotonin (5‐HT), oestradiol‐17β (E2) and progesterone (P4) were determined by means of enzyme‐linked immunosorbent assay and RIA, respectively. Intrafollicular 5‐HT, E2 and P4 concentrations were higher than systemic ones (p < .05). 5‐HT concentrations increased in larger compared to medium follicles, without differences compared to small size follicles (p < .05). 5‐HT and E2 (r = .79) and 5‐HT and P4 (r = .79; p < .05) were positively correlated. 5‐HT and P4 concentrations in follicular fluid increased progressively with the increase in follicular size (p < .05). Follicle diameter and E2 (r = .85) and P4 (r = .68) were correlated (p < .05). Since serotonin interacts with steroids, its role on steroidogenesis during growth of the dominant follicle may be suggested.
Linking fish trait responses to in‐stream habitat in reconstructed valley‐plugged stream reaches of the Coastal Plain, U.S.A.
Authors: Fore Jeffrey D. , Alford Amy B. , Blackwood David C. , Blanchard Tom A.
Published: August 2019

Valley‐plug formation is a challenging consequence of stream channelization especially in physiographic regions with highly erodible soils. Upstream channel degradation and incision results in accelerated sediment delivery processes wherein downstream aggradation decreases stream power and creates sand‐clogged channels. Channel reconstruction is now meeting hydrogeomorphic goals related to valley‐plug remediation, yet there exists a need to understand how this practice also facilitates ecological restoration. We evaluated fish trait response to in‐stream habitat conditions in channelized, recently restored, and “least‐disturbed” reference reaches of Coastal Plain streams in West Tennessee. Restored reaches were ecologically similar to channelized reaches, having higher proportions of nest‐guarding omnivores that were correlated with higher percentages of pool habitats and lower wetted width:depth ratios compared to reference reaches. Reference reaches had higher proportions of fast‐water dwelling and specialized insectivores that were correlated with high abundance of large woody debris, high‐wetted width:depth ratios, and low percentages of pool habitats. We conclude that in‐stream habitats in reconstructed channels have yet to promote reach‐scale ecological restoration relative to fish assemblage organization because trait‐habitat associations were not similar to reference conditions. However, our results lend to the development of ecological restoration targets that can be incorporated in future channel reconstruction projects in valley‐plugged, channelized streams of the Coastal Plain.
Airway inflammation in COPD: Is it worth measuring and is it clinically meaningful?
Authors: Simpson Jodie L.
Published: August 2019

See related Article
Cleansing‐induced changes in skin measured by in vivo confocal raman spectroscopy
Authors: Davies Mark A.
Published: August 2019

Background

One of the most important steps people can take in reducing the spread of bacteria and viruses is washing the hands with soap and water. Frequent washing, required in certain occupations, can lead to skin dryness, chapping, and itching.

Materials and methods

In vivo confocal Raman spectroscopy was used to study short‐term effects of hand washing on product deposition, lipid acyl chain structural disordering, and extraction of important skin components such as natural moisturizing factors, cholesterol, ceramides, amino acids, and changes in skin hydration. Effects of use of either soap, synthetic detergent, or triethanolamine (TEA)‐soap/ glycerin were compared at two water temperatures.

Results

Soap use resulted in significant deposition at all depths to 20 μm at 25°C and at the surface and 2 μm at 37°C. Significant decreases were observed in relative amounts of all skin components studied. NMF levels were not changed. Skin dehydration was observed for use of soap at 37°C.

Conclusions

Short‐term effects of frequent hand washing can be monitored with in vivo confocal Raman spectroscopy. Effects of frequent washing may be reduced with lower wash temperature and products. Skin dehydration is not associated with lipid chain disordering.
An Argument for the Law of Desire
Authors: Barnes Eric Christian
Published: August 2019

The law of desire has been proposed in several forms, but its essential claim is that agents always act on their strongest proximal action motivation. This law has threatening consequences for human freedom, insofar as it greatly limits agents’ ability to do otherwise given their motivational state. It has proven difficult to formulate a version that escapes counterexamples and some categorically deny its truth. Noticeable by its absence in the literature is any attempt to provide an argument for the law of desire – I propose such an argument here. It is noted that Sripada's “divided mind” theory of willpower provides a counterexample to the version of the law of desire my argument defends, but I note that a reformulated version of the law of desire survives this critique. I conclude that there is a serious case for the law of desire, and note the broader implications of this.
Experiential Explanation
Authors: Aronowitz Sara , Lombrozo Tania
Published: August 2019

People often answer why‐questions with what we call experiential explanations: narratives or stories with temporal structure and concrete details. In contrast, on most theories of the epistemic function of explanation, explanations should be abstractive: structured by general relationships and lacking extraneous details. We suggest that abstractive and experiential explanations differ not only in level of abstraction, but also in structure, and that each form of explanation contributes to the epistemic goals of individual learners and of science. In particular, experiential explanations support mental simulation and survive transitions across background theories; as a result, they support learning and help us translate between competing frameworks. Experiential explanations play an irreducible role in human cognition—and perhaps in science.
TRIX with treats: the considerable safety benefits of a transfusion medicine registry
Authors: Hauser Ronald G. , Hendrickson Jeanne E. , Tormey Christopher A.
Published: August 2019

See article on page 2559–2566, in this issue
Work‐up in the case of granulocyte antibodies
Authors: Flesch Brigitte
Published: August 2019

Granulocyte allo‐ and autoantibodies have been implicated in a variety of clinical conditions such as primary and secondary autoimmune neutropenia (AIN), alloimmune neutropenia (NAIN), transfusion‐related acute lung injury (TRALI) as well as febrile and severe pulmonary transfusion reactions. The classic granulocyte agglutination test (GAT) in combination with the granulocyte indirect immunofluorescence test (GIFT) can detect nearly all relevant antibodies. HNA‐1, ‐2, 4, 5 and HLA class I antibodies are clearly detectable in the GIFT while HNA‐3 antibodies strongly agglutinate neutrophils in the GAT. The glycoprotein‐specific and highly sensitive monoclonal antibody‐specific immobilization of granulocyte antigens (MAIGA) test detects all human neutrophil antigen (HNA) antibodies except for HNA‐3 but is time‐consuming and requires highly skilled personnel. For TRALI diagnostics, laboratory testing is completed by the indirect lymphocyte immunofluorescence test (LIFT), and HLA class I and II ELISAs or fluorescent bead‐based assays (Luminex). The latter also enable faster and more automated HNA antibody detection but to date not all specificities, especially HNA‐3, can be reliably detected so that still the classical tests have to complete the methodological spectrum. HNA allelotyping by PCR methods is the first choice for all HNA except for HNA‐2 because the molecular reason for the HNA‐2null phenotype is not completely understood. Establishing a PCR‐SSP reaction for the main CD177*787A>T polymorphism comprises the risk to miss other causes so that HNA‐2 is still typed serologically. Granulocyte serology even today is widely based on a variety of manual methods, requires experienced laboratory staff and profound knowledge of granulocyte immunobiology.
On some incomplete theta integrals
Authors: Funke Jens , Kudla Stephen
Published: August 2019

In this paper we construct indefinite theta series for lattices of arbitrary signature $(p,q)$ as ‘incomplete’ theta integrals, that is, by integrating the theta forms constructed by the second author with J. Millson over certain singular $q$-chains in the associated symmetric space $D$. These chains typically do not descend to homology classes in arithmetic quotients of $D$, and consequently the theta integrals do not give rise to holomorphic modular forms, but rather to the non-holomorphic completions of certain mock modular forms. In this way we provide a general geometric framework for the indefinite theta series constructed by Zwegers and more recently by Alexandrov, Banerjee, Manschot, and Pioline, Nazaroglu, and Raum. In particular, the coefficients of the mock modular forms are identified with intersection numbers.
Mercantilización del maíz en un contexto político y de cambio climático en el trópico subhúmedo mexicano
Authors: CASANOVA-PÉREZ LORENA , MARTÍNEZ-DÁVILA JUAN PABLO , LÓPEZ-ORTIZ SILVIA , ROSALES-MARTÍNEZ VERÓNICA
Published: August 2019

En México, los efectos de los ajustes estructurales en los años 90 del siglo pasado y del cambio climático han provocado mayor vulnerabilidad en la agricultura del trópico subhúmedo. El estudio de este proceso requirió la realización de una encuesta y de entrevistas a profundidad, además de una revisión documental. Los resultados muestran que en el área de estudio se ha abandonado el cultivo de maíz nativo y se ha sustituido por maíz mejorado, cuya producción tiene como fin satisfacer la demanda nacional e internacional. Esto condujo a un proceso de individualización de la producción que ha roto la confianza y la solidaridad social, recursos valiosos para hacer frente al cambio climático.
The Biosphere Reserves of Spain during 2008-2014: Implementation and Key Aspects for its Management
Authors: Castaño-Quintero Paula Andrea , Gil-Cerezo María Victoria , Galán Soldevilla Carmen , Domínguez-Vilches Eugenio
Published: August 2019

The Spanish Network of Biosphere Reserves (SNBR) has a monitoring programme enabling its degree of consolidation to be ascertained, as well as the levels of implementation and territorial assimilation of the Biosphere Reserves that it comprises. The statistical analysis carried out on the results of the SNBR implementation indicators for the period 2008–2014 stand out three fundamental aspects: i) two phases of implementation, ii) the improvements in the indicator scores in the second phase, and iii) the influence of the indicators on the levels of implementation achieved. Some key aspects are noted that could contribute to the enhancement of the implementation of these reserves.
An Experimental Investigation of the Air-Side Pressure Drop Through a Bare Tube Bundle
Authors: du Plessis Jacques , Owen Michael
Published: August 2019

Presented in this paper is an experimental investigation of the steady-state air-side pressure drop through a delugable bare tube bundle. The tube bundle forms a part of a systematic investigation of the subcomponents of a hybrid dry/wet dephlegmator (HDWD), also known as a secondary steam condenser, used in direct dry-cooling. A modular bare tube bundle is designed and built to experimentally investigate the pressure drop in a counter-flow test facility with 19 mm and 25 mm tubes at various tube depths. The tests are conducted under both dry and wet (deluged) operating modes. The test results are used to develop empirical correlations for both dry and wet operating modes. The absolute average error is found to be 3.2% between the measured and predicted values for the dry correlation and for the wet correlation the absolute average error is found to be 4.5%. The newly developed correlation is used in a thermal case study to illustrate the effect of the under- and overprediction that the air-side pressure drop will have on a relatively small evaporative cooler where two cases corresponding to fan power consumptions of 1.1 kW and 5.5 kW were considered.
Coping as a Mediation Mechanism Between Severity of Spectator Dysfunctional Behavior and Revisit Intention: The Moderating Effects of Self-Construal in Sport Consumption
Authors: Kim Kyungyeol (Anthony) , Byon Kevin K. , Pedersen Paul M.
Published: August 2019

The stress and coping theory posits that in the face of negative consumption situations, individuals experience a sequential process: primary appraisal, secondary appraisal, and behavioral outcomes. Drawing on the theory, the purpose of the study is to test (a) the mediating effects of coping strategies (i.e., secondary appraisal) between the severity of spectator dysfunctional behavior (SDB; i.e., primary appraisal) and revisit intention and (b) the moderating effects of self-construal (i.e., interdependence vs. independence). Across two studies, using a survey experiment (Study 1) and a repeated-measures survey experiment (Study 2), the findings indicate that coping strategies (i.e., active, expressive, and denial coping) significantly and uniquely mediated the relationship between the severity of SDB (high vs. low) and revisit intention. Furthermore, in responding to highly severe SDB, spectators with interdependent self-construal engaged more in active and expressive coping, and less in denial coping and revisit intention than those with independent self-construal. Overall, the present study highlights (a) the importance of coping strategies for a clearer understanding of the SDB–revisit intention relationship and (b) a boundary condition of self-construal for the influences of SDB on coping strategies and revisit intention.
Resistance and Heteroresistance to Colistin in Pseudomonas aeruginosa Isolates from Wenzhou, China
Authors: Lin Jie , Xu Chunquan , Fang Renchi , Cao Jianming , Zhang Xiucai , Zhao Yajie , Dong Guofeng , Sun Yao , Zhou Tieli
Published: August 2019

The goal was to investigate the mechanisms of colistin resistance and heteroresistance in
Pseudomonas aeruginosa
clinical isolates. Colistin resistance was determined by the broth microdilution method. Colistin heteroresistance was evaluated by population analysis profiling. Time-kill assays were also conducted. PCR sequencing was performed to detect the resistance genes among (hetero)resistant isolates, and quantitative real-time PCR assays were performed to determine their expression levels.
Metabolite Cross-Feeding between Rhodococcus ruber YYL and Bacillus cereus MLY1 in the Biodegradation of Tetrahydrofuran under pH Stress
Authors: Liu Zubi , Huang Hui , Qi Minbo , Wang Xuejun , Adebanjo Omosalewa O. , Lu Zhenmei
Published: August 2019

Rhodococcus
species have been discovered in diverse environmental niches and can degrade numerous recalcitrant toxic pollutants. However, the pollutant degradation efficiency of these strains is severely reduced due to the complexity of environmental conditions and limitations in the growth of the pollutant-degrading microorganism. In our study,
Bacillus cereus
strain MLY1 exhibited strong stress resistance to adapt to various environments and improved the THF degradation efficiency of
Rhodococcus ruber
YYL by a metabolic cross-feeding interaction style to relieve the pH stress. These findings suggest that metabolite cross-feeding occurred in a complementary manner, allowing a pollutant-degrading strain to collaborate with a nondegrading strain in the biodegradation of various recalcitrant compounds. The study of metabolic exchanges is crucial to elucidate mechanisms by which degrading and symbiotic bacteria interact to survive environmental stress.
A Study Investigating Markers in PLeural Effusion (SIMPLE): a prospective and double-blind diagnostic study
Authors: Han Yan-Qiu , Yan Li , Li Peng , Zhang Lei , Ouyang Pei-Heng , Hu Zhi-De
Published: August 2019

Introduction

Serum and fluid laboratory markers are valuable for exploring the aetiologies of pleural effusion (PE) because of their relative non-invasiveness, low cost, objective result and short turnaround time. The diagnostic accuracy of these potential markers needs to be rigorously evaluated before their widespread application in clinical practice. Here, we plan to perform a Study Investigating Markers in PLeural Effusion (SIMPLE).

Methods and analysis

This is a prospective and double-blind clinical trial which is being performed at the Affiliated Hospital of Inner Mongolia Medical University, China. Adult patients admitted for the evaluation of aetiology of PE from September 2018 to July 2021 will be enrolled after informed consent. Pleural fluid and serum specimens will be collected and stored at –80°C for the laboratory analysis. The final diagnosis will be concurred with further imaging, microbiology, cytology and biopsy if needed. The results of investigated laboratory markers will be unknown to the clinicians who will make diagnosis and the clinical diagnoses will be unknown to the laboratory technicians who will determine markers. The diagnostic accuracy of investigated markers will be assessed using receiver operating characteristics (ROC) curve analysis, multivariable logistic regression model, decision curve analysis (DCA), net reclassification index (NRI) and integrated discriminatory index (IDI).

Ethics and Dissemination

The study is approved by the Ethic Committee of the Affiliated Hospital of Inner Mongolia Medical University (NO: 2018011). The results of SIMPLE will be submitted to international scientific peer-reviewed journals or conferences in laboratory medicine or respiratory medicine, thoracic diseases.

Trial registration number

Chinese Clinical Trial Registry (ChiCTR1800017449); Pre-results.
Pilot study to build capacity for family medicine with abbreviated, low-cost training programme with minimal impact on patient care for a cohort of 84 general practitioners caring for Palestinian refugees in Jordan
Authors: Al Shdaifat Amjad , Zink Therese
Published: August 2019

Purpose

Studies document that primary care improves health outcomes and controls costs. In regions of the world where primary care is underdeveloped, building capacity is essential. Most capacity building programmes are expensive and take physicians away from their clinical settings. We describe a programme created, delivered and evaluated from 2013 to 2014 in Jordan.

Design

Cohort study.

Setting

Physicians providing primary care in the United Nations Relief and Works Agency for Palestine Refugees clinics in Jordan.

Participants

Eighty-four general practitioners (GPs) were invited to participate and completed the training and evaluation. GPs are physicians who have a license to practice medicine after completing medical school and a 1 year hospital-based rotating internship. Although GPs provide care in the ambulatory setting, their hospital-based education provides little preparation for delivering ambulatory primary care.

Intervention/Programme

This three-stage programme included needs assessment, didactics and on-the-job coaching. First, the learning needs and baseline knowledge of the trainees were assessed and the findings guided curriculum development. During the second stage, 48 hours of didactics covered topics such as communications skills and disease management. The third stage was delivered one on one in the trainee’s clinical setting for a 4 to 6-hour block. The first, middle and final patient interactions were evaluated.

Primary and secondary outcome measures

Preknowledge and postknowledge assessments were compared. The clinical checklist, developed for the programme, assessed eight domains of clinical skills such as communication and history taking on a five-point Likert scale during the patient interaction.

Results

Preknowledge and postknowledge assessments demonstrated significantly improved scores, 46% to 81% (p<0.0001). Trainee’s clinical checklist scores improved over the assessment intervals. Satisfaction with the training was high.

Conclusion

This programme is a potential model for building primary care capacity at low cost and with little impact on patient care that addresses both knowledge and clinical skills on the job.
Paediatric goal management training in patients with acquired brain injury: study protocol for a randomised controlled trial
Authors: Hypher Ruth Elizabeth , Brandt Anne Elisabeth , Risnes Kari , Rø Torstein Baade , Skovlund Eva , Andersson Stein , Finnanger Torun Gangaune , Stubberud Jan
Published: August 2019

Introduction

Compromised integrity of the brain due to paediatric acquired brain injury (pABI) has been associated with cognitive impairment, particularly executive dysfunction, in addition to somatic and emotional symptoms and reduced everyday function. Goal Management Training (GMT) is a cognitive rehabilitation intervention for improving executive function (EF) that has received empirical support in studies of adults with ABI. The purpose of the present study is to determine the efficacy of a recently developed paediatric version of GMT (pGMT) for children and adolescents with ABI and reported executive dysfunction.

Methods and analysis

This study protocol describes a parallel randomised controlled trial including allocation concealment and assessor blinding. Eighty survivors after pABI, aged 10–17 years at the time of intervention, will be recruited. Participants will be randomly allocated to either pGMT (n=40) or a psychoeducative control intervention (n=40; paediatric Brain Health Workshop). Both interventions consist of seven group sessions for participants and parents, followed by external cueing and telephone counselling. The study also includes involvement of teachers. Assessments will be performed at baseline, immediately postintervention and at 6 months’ follow-up. Primary outcome measure will be changes in daily life EF as reported by parents (The Behavior Rating Inventory of Executive Function). Secondary outcomes include other assessments of EF (neuropsychological tests and questionnaires). Furthermore, we aim to assess generalisation effects of pGMT on other cognitive functions, as well as emotional, behavioural, adaptive and family function, academic performance, fatigue and quality of life.

Ethics and dissemination

Results from this study will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals, in addition to presentations at scientific conferences. The study will be conducted in accordance with the Helsinki declaration and the Ethical Research Involving Children (ChildWatch International and Unicef). In accordance to Good Clinical Practice our study includes safety and quality monitoring guarantees in compliance with research ethics and safety. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials 2010 statement and Standard Protocol Items for Reporting in Trials recommendations, in addition to being registered at ClinicalTrials.gov. The study has been approved by the Regional Committees for Medical and Health Research Ethics Norway (2017/772).

Trial registration number

NCT03215342.
Protocol for a feasibility randomised controlled trial of a musculoskeletal exercise intervention versus usual care for children with haemophilia
Authors: Hashem Ferhana , Bladen Melanie , Carroll Liz , Dodd Charlene , Drechsler Wendy I , Lowery David , Patel Vishal , Pellatt-Higgins T , Saloniki Eirini , Stephensen David
Published: August 2019

Introduction

Haemophilia is a rare, inherited disorder in which blood does not clot normally, resulting in bleeding into joints and muscles. Long-term consequence is disabling joint pain, stiffness, muscle weakness, atrophy and reduced mobility. The purpose of this proposed feasibility of a randomised controlled trial (RCT) is to test the feasibility of an age-appropriate physiotherapy intervention designed to improve muscle strength, posture and the way boys use their joints during walking and everyday activities.

Methods and analysis

A small-scale two-centre RCT of a 12-week muscle strengthening exercise intervention versus usual care for young children with haemophilia will be conducted. Primary outcomes will be safety and adherence to the exercise intervention. Secondary outcomes will include recruitment, retention and adverse event rates, clinical data, muscle strength, joint biomechanics and foot loading patterns during walking, 6 min timed walk, timed-up-and-down-stairs, EQ-5D-Y, participants’ perceptions of the study, training requirements and relevant costs. Recruitment, follow-up, safety and adherence rates will be described as percentages. Participant diary and interview data will be analysed using a framework analysis. Demographic and disease variable distributions will be analysed for descriptive purposes and covariant analysis. Estimates of differences between treatment arms (adjusted for baseline) and 75% and 95% CIs will be calculated.

Ethics and dissemination

The study has ethical approval from the London—Fulham Research Ethics Committee (17/LO/2043) as well as Health Research Authority approval. As well as informing the design of the definitive trial, results of this study will be presented at local, national and international physiotherapy and haemophilia meetings as well as manuscripts submitted to peer-reviewed journals. We will also share the main findings of the study to all participants and the Haemophilia Society.
Hygrothermal performance of New Zealand wall constructions — meeting the durability requirements of the New Zealand Building Code
Authors: Overton G.
Published: August 2019

The New Zealand Building Code (NZBC) is performance based. From a durability perspective, compliance requires a practitioner to demonstrate that materials will remain functional for the minimum periods specified. The NZBC also states that buildings must be constructed to avoid the likelihood of fungal growth or the accumulation of contaminants on linings and other building elements. Currently, there is no recognised method for practitioners to use to demonstrate that a wall system can meet this requirement for the required design life. In this paper, we consider how hygrothermal modelling, in conjunction with the VTT mould index, may be used to form the basis of such a method. In the past, there has been a discrepancy between predicted failures and field evidence, but the VTT mould index appears to correlate much better with the successful in-service history of typical New Zealand construction.
ENTREPRENEURIAL ORIENTATION AND GROWTH POTENTIAL OF MICROENTERPRISES IN NORTHWEST, NIGERIA
Authors: GARBA ABUBAKAR S. , KABIR IBRAHIM , MAHMOUD MAHMOUD A.
Published: August 2019

The purpose of this study is to explore the entrepreneurial orientation (EO) and growth potential of microenterprises. To test the research hypotheses, multiple regression and multivariate analysis of variance (MANOVA) were used. Multiple regression was used in explaining how well EO predicts microenterprises growth potential. MANOVA compares the groups and indicates whether the mean differences between the groups on the combination of dependent variables are likely to have occurred by chance. Our study contributes to the literature by exploring the growth potential of the existing microenterprises and explains its relationship to owners’ EO in both urban and rural informal sectors.
Mitochondria-targeted tri-triphenylphosphonium substituted meso-tetra(4-carboxyphenyl)porphyrin(TCPP) by conjugation with folic acid and graphene oxide for improved photodynamic therapy
Authors: Yang Chen , Zhang Hongyue , Wang Zhiqiang , Wu Xiaodan , Jin Yingxue
Published: August 2019

Mitochondria are extensively researched as target sites to maximize photodynamic therapy (PDT) effects because they play crucial roles in metabolism. Here, a mitochondria targeting PDT agent, tri-triphenylphosphonium substituted meso-tetra(4-carboxyphenyl)porphyrin (TCPP-TPP) is prepared for the first time. Considering that many porphyrin derivatives are quick to aggregate, thereby reducing the PDT effect, our photosensitizer (PS) was loaded on a folic acid (FA) decorated graphene oxide (GO) nanosystem, called GF@TCPP-TPP, by electrostatic and [Formula: see text]–[Formula: see text] stacking or hydrophobic cooperative interactions, to improve the transportation of photosensitizers and enhance the therapeutic effect. Herein, we have performed a detailed study of photodynamic activity of GF@TCPP-TPP nanocomposites and evaluated their potential as a photosensitizer in PDT. An MTT assay showed that GF@TCPP-TPP inhibited HeLa cells in a concentration-dependent manner under light (650 ± 10 nm, 5 mW [Formula: see text] and 10 min), and presented remarkably improved PDT efficiency (IC[Formula: see text] g [Formula: see text] mL[Formula: see text] of equivalent TCPP-TPP) over free TCPP (IC[Formula: see text] after irradiation. Furthermore, our research indicated that Type I mechanisms (the generation of hydroxyl radicals) play a predominant role in the GF@TCPP-TPP induced PDT process. This coincides with the low singlet oxygen (1O[Formula: see text] quantum yield ([Formula: see text] [Formula: see text] 33.6%) in a DMF solution. Moreover, cell morphological changes after GF@TCPP-TPP PDT further demonstrated that GF@TCPP-TPP could induce damage and apoptotic cell death efficiently. In particular, precise delivery of photosensitizers to mitochondria was proven by organelle localization.
Optimized protocols for isolation, fixation, and flow cytometric characterization of leukocytes in ischemic hearts
Authors: Covarrubias Roman , Ismahil Mohamed Ameen , Rokosh Gregg , Hamid Tariq , Accornero Federica , Singh Harpreet , Gumina Richard J. , Prabhu Sumanth D. , Bansal Shyam S.
Published: August 2019

Immune activation post-myocardial infarction is an orchestrated sequence of cellular responses to effect tissue repair and healing. However, excessive and dysregulated inflammation can result in left ventricular remodeling and pathological alterations in the structural and mechanical attributes of the heart. Identification of key pathways and critical cellular mediators of inflammation is thus essential to design immunomodulatory therapies for myocardial infarction and ischemic heart failure. Despite this, the experimental approaches to isolate mononuclear cells from the heart are diverse, and detailed protocols to enable maximum yield of live cells in the shortest time possible are not readily available. Here, we describe optimized protocols for the isolation, fixation, and flow cytometric characterization of cardiac CD45+leukocytes. These protocols circumvent time-consuming coronary perfusion and density-mediated cell-separation steps, resulting in high cellular yields from cardiac digests devoid of contaminating intravascular cells. Moreover, in contrast to methanol and acetone, we show that cell fixation using 1% paraformaldehyde is most optimal as it does not affect antibody binding or cellular morphology, thereby providing a considerable advantage to study activation/infiltration-associated changes in cellular granularity and size. These are highly versatile methods that can easily be streamlined for studies requiring simultaneous isolation of immune cells from different tissues or deployment in studies containing a large cohort of samples with time-sensitive constraints.

NEW & NOTEWORTHY In this article, we describe optimized protocols for the isolation, fixation, and flow cytometric analysis of immune cells from the ischemic/nonischemic hearts. These protocols are optimized to process several samples/tissues, simultaneously enabling maximal yield of immune cells in the shortest time possible. We show that the low-speed centrifugation can be used as an effective alternative to lengthy coronary perfusion to remove intravascular cells, and sieving through 40-μm filter can replace density-mediated mononuclear cell separation which usually results in 50–70% cell loss in the sedimented pellets. We also show that cell fixation using 1% paraformaldehyde is better than the organic solvents such as methanol and acetone for flow cytometric analysis.
Medial prefrontal cortex in neurological diseases
Authors: Xu Pan , Chen Ai , Li Yipeng , Xing Xuezhi , Lu Hui
Published: August 2019

The medial prefrontal cortex (mPFC) is a crucial cortical region that integrates information from numerous cortical and subcortical areas and converges updated information to output structures. It plays essential roles in the cognitive process, regulation of emotion, motivation, and sociability. Dysfunction of the mPFC has been found in various neurological and psychiatric disorders, such as depression, anxiety disorders, schizophrenia, autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, and addiction. In the present review, we summarize the preclinical and clinical studies to illustrate the role of the mPFC in these neurological diseases.
Characterization of eQTLs associated with androstenone by RNA sequencing in porcine testis
Authors: Drag Markus H. , Kogelman Lisette J. A. , Maribo Hanne , Meinert Lene , Thomsen Preben D. , Kadarmideen Haja N.
Published: August 2019

Characterization of genetic variants affecting genome-wide gene expression levels (expression quantitative trait loci or eQTLs) in pig testes may improve our understanding of genetic architecture of boar taint (an animal welfare trait) and helps in genome-assisted or genomic selection programs. The aims of this study were to identify eQTLs associated with androstenone, to find candidate eQTLs for low androstenone, and to validate the top eQTL by reverse transcriptase quantitative PCR (RT-qPCR). Gene expression profiles were obtained by RNA sequencing in testis from Danish cross-bred pigs and genotype data by 80K single nucleotide polymorphism panel. A total of 262 eQTLs [false discovery rate (FDR) < 0.05] were identified by using two software packages: Matrix eQTL and Krux eQTL. Of these, 149 cis-acting eQTLs were significantly associated with androstenone concentrations and gene expression (FDR < 0.05). The eQTLs were associated with several genes of boar taint relevance including CYP1A2, CYB5D1, and SPHK2. One eQTL gene, AMPH, was differentially expressed (FDR < 0.05) and affected by chicory. Five candidate eQTLs associated with low androstenone concentrations were discovered, including the top eQTL associated with CYP1A2. RT-qPCR confirmed target gene expression to be significantly ( P < 0.05) different based on eQTL genotypes. Furthermore, eQTLs were enriched as QTLs for 15 boar taint related traits from the PigQTLdb. This is the first study to report eQTLs in testes of commercial crossbred pigs used in pork production and to reveal genetic architecture of boar taint. Potential applications include development of a DNA test and in advanced genomic selection models for boar taint.
Sensory Processing at Ribbon Synapses in the Retina and the Cochlea
Authors: Moser Tobias , Grabner Chad P. , Schmitz Frank
Published: August 2019

In recent years, sensory neuroscientists have made major efforts to dissect the structure and function of ribbon synapses which process sensory information in the eye and ear. This review aims to summarize our current understanding of two key aspects of ribbon synapses: 1) their mechanisms of exocytosis and endocytosis and 2) their molecular anatomy and physiology. Our comparison of ribbon synapses in the cochlea and the retina reveals convergent signaling mechanisms, as well as divergent strategies in different sensory systems.
A Fatty Acid Oxidation-dependent Metabolic Shift Regulates the Adaptation of BRAF-mutated Melanoma to MAPK Inhibitors
Authors: Aloia Andrea , Müllhaupt Daniela , Chabbert Christophe D. , Eberhart Tanja , Flückiger-Mangual Stefanie , Vukolic Ana , Eichhoff Ossia , Irmisch Anja , Alexander Leila T. , Scibona Ernesto , Frederick Dennie T. , Miao Benchun , Tian Tian , Cheng Chaoran , Kwong Lawrence N. , Wei Zhi , Sullivan Ryan J. , Boland Genevieve M. , Herlyn Meenhard , Flaherty Keith T. , Zamboni Nicola , Dummer Reinhard , Zhang Gao , Levesque Mitchell P. , Krek Wilhelm , Kovacs Werner J.
Published: August 2019

Purpose:

Treatment of BRAFV600E-mutant melanomas with MAPK inhibitors (MAPKi) results in significant tumor regression, but acquired resistance is pervasive. To understand nonmutational mechanisms underlying the adaptation to MAPKi and to identify novel vulnerabilities of melanomas treated with MAPKi, we focused on the initial response phase during treatment with MAPKi.

Experimental Design:

By screening proteins expressed on the cell surface of melanoma cells, we identified the fatty acid transporter CD36 as the most consistently upregulated protein upon short-term treatment with MAPKi. We further investigated the effects of MAPKi on fatty acid metabolism using in vitro and in vivo models and analyzing patients' pre- and on-treatment tumor specimens.

Results:

Melanoma cells treated with MAPKi displayed increased levels of CD36 and of PPARα-mediated and carnitine palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO). While CD36 is a useful marker of melanoma cells during adaptation and drug-tolerant phases, the upregulation of CD36 is not functionally involved in FAO changes that characterize MAPKi-treated cells. Increased FAO is required for BRAFV600E-mutant melanoma cells to survive under the MAPKi-induced metabolic stress prior to acquiring drug resistance. The upfront and concomitant inhibition of FAO, glycolysis, and MAPK synergistically inhibits tumor cell growth in vitro and in vivo.

Conclusions:

Thus, we identified a clinically relevant therapeutic approach that has the potential to improve initial responses and to delay acquired drug resistance of BRAFV600E-mutant melanoma.
Tumor Growth Rate as a Validated Early Radiological Biomarker Able to Reflect Treatment-Induced Changes in Neuroendocrine Tumors: The GREPONET-2 Study
Authors: Lamarca Angela , Ronot Maxime , Moalla Salma , Crona Joakim , Opalinska Marta , Lopez Lopez Carlos , Pezzutti Daniela , Najran Pavan , Carvhalo Luciana , Bezerra Regis Otaviano Franca , Borg Philip , Vietti Violi Naik , Vidal Trueba Hector , de Mestier Louis , Scaefer Niklaus , Baudin Eric , Sundin Anders , Costa Frederico , Pavel Marianne , Dromain Clarisse
Published: August 2019

Purpose:

Tumor growth rate (TGR) represents the percentage change in tumor volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR3m) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in neuroendocrine tumors (NET).

Experimental Design:

Patients from 7 centers with advanced grade (G) 1/2 NETs from the pancreas (P)/small bowel (SB) initiating ST/WW were eligible. Computed tomography (CT)/MRI performed at prebaseline, baseline, and 3(±1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (ΔTGR3m-BL; paired T test), and Aim-2: validate TGR3m (<0.8%/m vs. ≥0.8%/m) as an early biomarker in an independent cohort (Kaplan–Meier/Cox regression).

Results:

Of 785 patients screened, 127 were eligible. Mean (SD) TGR0 and TGR3m were 5.4%/m (14.9) and −1.4%/m (11.8), respectively. Mean (SD) ΔTGR3m-BL paired-difference was −6.8%/m (19.3; P < 0.001). Most marked ΔTGR3m-BL [mean (SD)] were identified with targeted therapies [−11.3%/m (4.7); P = 0.0237] and chemotherapy [−7.9%/m (3.4); P = 0.0261]. Multivariable analysis confirmed the absence of previous treatment (OR = 4.65; 95% CI, 1.31–16.52; P = 0.018) and low TGR3m (continuous variable; OR 1.09; 95% CI, 1.01–1.19; P = 0.042) to be independent predictors of radiologic objective response. When the multivariable survival analysis for PFS (Cox regression) was adjusted to grade (P = 0.004) and stage (P = 0.017), TGR3m ≥ 0.8 (vs. <0.8) maintained its significance as a prognostic factor (P < 0.001), whereas TGR0 and ΔTGR3m-BL did not. TGR3m ≥ 0.8%/m was confirmed as an independent prognostic factor for PFS [external validation; Aim-2; multivariable HR 2.21 (95% CI, 1.21–3.70; P = 0.003)].

Conclusions:

TGR has a role as a biomarker for monitoring response to therapy for early identification of treatment-induced changes and for early prediction of PFS and radiologic objective response.
Antitumor T-cell Homeostatic Activation Is Uncoupled from Homeostatic Inhibition by Checkpoint Blockade
Authors: Marshall Netonia , Hutchinson Keino , Marron Thomas U. , Aleynick Mark , Hammerich Linda , Upadhyay Ranjan , Svensson-Arvelund Judit , Brown Brian D. , Merad Miriam , Brody Joshua D.
Published: August 2019

T-cell transfer into lymphodepleted recipients induces homeostatic activation and potentiates antitumor efficacy. In contrast to canonical T-cell receptor–induced activation, homeostatic activation yields a distinct phenotype and memory state whose regulatory mechanisms are poorly understood. Here, we show in patients and murine models that, following transfer into lymphodepleted bone marrow transplant (BMT) recipients, CD8+ T cells undergo activation but also simultaneous homeostatic inhibition manifested by upregulation of immune-checkpoint molecules and functional suppression. T cells transferred into BMT recipients were protected from homeostatic inhibition by PD-1/CTLA4 dual checkpoint blockade (dCB). This combination of dCB and BMT—”immunotransplant”—increased T-cell homeostatic activation and antitumor T-cell responses by an order of magnitude. Like homeostatic activation, homeostatic inhibition is IL7/IL15-dependent, revealing mechanistic coupling of these two processes. Marked similarity in ex vivo modulation of post-BMT T cells in mice and patients is promising for the clinical translation of immunotransplant (NCT03305445) and for addressing homeostatic inhibition in T-cell therapies.

Significance:

For optimal anticancer effect, T-cell therapies including chimeric antigen receptor T-cell, tumor-infiltrating lymphocyte, and transgenic T-cell therapies require transfer into lymphodepleted recipients and homeostatic activation; however, concomitant homeostatic inhibition mitigates T-cell therapies' efficacy. Checkpoint blockade uncouples homeostatic inhibition from activation, amplifying T-cell responses. Conversely, tumors nonresponsive to checkpoint blockade or BMT are treatable with immunotransplant.

See related commentary by Ansell, p. 1487.

This article is highlighted in the In This Issue feature, p. 1469
POUR LA TRADUCTION
Authors: Riaudel Michel
Published: August 2019

Dans le présent exposé, nous traiterons des voies possibles que nous offre la traduction : parler dans sa langue, dans la langue de l’autre ; parler dans ma langue ; adopter une langue tierce, une sorte de lingua franca. Comprendre la langue de l’autre ne peut nous dispenser de traduire, c’est-à-dire d’acclimater, de s’approprier, mais de mobiliser et de confronter des épistémologies, faire jouer des mondes entre eux et contre eux. Pour ce faire, nous convoquerons, d’un côté, l’anthropologie d’Eduardo Viveiros de Castro et le concept de « transduction » et, de l’autre, Antoine Berman et le lien entre le travail critique d’interprétation et la traduction.
EROS E A GRÉCIA NO CORAÇÃO DE TRÊS CONTOS DE MARGUERITE YOURCENAR
Authors: Chauvel Thaïs
Published: August 2019

Este artigo propõe analisar o tratamento da temática eróticoamorosa nas seguintes nouvelles de Marguerite Yourcenar: “Le sourire de Marko”, “Le dernier amour du prince Genghi” e “La veuve Aphrodissia”. Escritas e publicadas originalmente de forma separada, em 1938 essas narrativas foram reunidas numa antologia organizada pela autora e intitulada Nouvelles Orientales. Trata-se de uma de suas obras de juventude na qual eros é um dos temas principais. O objetivo desse estudo é mostrar de que maneira a paixão e o amor retratados por Yourcenar nestes textos dialoga intimamente com representação de eros na poesia grega arcaica, notadamente com a lírica de Safo, no intuito de verificar o modo como a escritora apropria-se, em pleno século XX, de uma representação clássica do amor, legitimando, assim, o tratamento da paixão e do amor carnal.
AS IMAGENS DO BRASIL NO ROMANCE “LÀ OÙ LES TIGRES SONT CHEZ EUX” E EM SUA TRADUÇÃO
Authors: Camargo Raquel Peixoto do Amaral
Published: August 2019

O presente trabalho, fruto do andamento de uma pesquisa de doutorado, busca investigar imagensdo Brasil no romance de Jean-Marie Blàs de Roblès, Làoùles tigres sont chez eux, e na sua tradução brasileira, Lá onde os tigres se sentem em casa, de Maria de Fátima Oliva do Coutto e Mauro Pinheiro.A partir da seleção de imagotipos – conceito caro à Imagologia e que difere dos estereótipos por se referir a imagens menos cristalizadas –explicitaremos algumas ideias que estão por trás das imagens veiculadas no romance francês e observaremos as suas refrações na tradução brasileira. Nós nos ateremos, principalmente, às passagens do livro de Roblès que evidenciam encontros entre culturas e nas quais a presença da alteridade se dá de forma marcante. Pretende-se, com a análise dos imagotipos literários levantados, descreveras diferenças entre umas e outras imagens e perceber a extensão do campo semântico dessas diferenças.