bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of PopZ

At

activity in
Agrobacterium tumefaciens
by Deletion or Depletion Leads to Multiple Growth Poles, Minicells, and Growth Defects
Authors: Grangeon Romain , Zupan John , Jeon Yeonji , Zambryski Patricia C.
Published: November 2017

Agrobacterium tumefaciens
grows by addition of peptidoglycan (PG) at one pole of the bacterium. During the cell cycle, the cell needs to maintain two different developmental programs, one at the growth pole and another at the inert old pole. Proteins involved in this process are not yet well characterized. To further characterize the role of pole-organizing protein
A. tumefaciens
PopZ (PopZ

At

), we created deletions of the five PopZ

At

domains and assayed their localization. In addition, we created a
popZ

At

deletion strain (Δ
popZ

At

) that exhibited growth and cell division defects with ectopic growth poles and minicells, but the strain is unstable. To overcome the genetic instability, we created an inducible PopZ

At

strain by replacing the native ribosome binding site with a riboswitch. Cultivated in a medium without the inducer theophylline, the cells look like Δ
popZ

At

cells, with a branching and minicell phenotype. Adding theophylline restores the wild-type (WT) cell shape. Localization experiments in the depleted strain showed that the domain enriched in proline, aspartate, and glutamate likely functions in growth pole targeting. Helical domains H3 and H4 together also mediate polar localization, but only in the presence of the WT protein, suggesting that the H3 and H4 domains multimerize with WT PopZ

At

, to stabilize growth pole accumulation of PopZ

At

.

IMPORTANCE
Agrobacterium tumefaciens
is a rod-shaped bacterium that grows by addition of PG at only one pole. The factors involved in maintaining cell asymmetry during the cell cycle with an inert old pole and a growing new pole are not well understood. Here we investigate the role of PopZ

At

, a homologue of
Caulobacter crescentus
PopZ (PopZ

Cc

), a protein essential in many aspects of pole identity in
C. crescentus
. We report that the loss of PopZ

At

leads to the appearance of branching cells, minicells, and overall growth defects. As many plant and animal pathogens also employ polar growth, understanding this process in
A. tumefaciens
may lead to the development of new strategies to prevent the proliferation of these pathogens. In addition, studies of
A. tumefaciens
will provide new insights into the evolution of the genetic networks that regulate bacterial polar growth and cell division.
Biomarkers of tubulointerstitial damage and function in type 1 diabetes
Authors: de Boer Ian H , Gao Xiaoyu , Bebu Ionut , Hoofnagle Andrew N , Lachin John M , Paterson Andrew , Perkins Bruce A , Saenger Amy K , Steffes Michael W , Zinman Bernard , Molitch Mark E
Published: November 2017

Objective

To evaluate biomarkers of renal tubulointerstitial damage and function in type 1 diabetes with and without diabetic kidney disease.

Research design and methods

Cross-sectional case-control study of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants. Cases (N=43) had incident persistent estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2with urinary albumin excretion>300 mg/24 hour. Controls (N=43) had persistent eGFR>90 mL/min/1.73 m2and urinary albumin excretion <30 mg/24 hour. Urinary and plasma biomarkers reflecting tubular injury, inflammation, fibrosis, secretion, and synthetic function were measured from stored specimens collected at the first study visit with reduced eGFR (for case participants) or the corresponding study year (for control participants).

Results

Mean (SD) age was 51 (9) and 50 (8) years for case and control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5) years, respectively. Mean (SD) eGFR was 39 (14) and 103 (9) mL/min/1.73 m2for case and control participants, and mean (SD) albumin excretion rate was 1978 (2914) and 10 (7) mg/day, respectively. Comparing cases with controls, significant differences were observed in each measured biomarker, including urine epidermal growth factor (mean 5.3 vs 21.2 μg/g creatinine for case vs control participants, respectively), urine monocyte chemoattractant protein-1 (596 vs 123 ng/g creatinine), urine galectin-3 (168 vs 52 μg/g creatinine), plasma soluble tubular necrosis factor receptor-1 (3695 vs 1022 pg/mL), plasma galectin-3 (21.3 vs 11.0 ng/mL), urinary clearances of hippurate (70 vs 167 mL/min) and cinnamoylglycine (77 vs 317 mL/min), and plasma arginine-citrulline ratio (5.6 vs 7.7 μg/μg), each P<0.001.

Conclusions

Marked abnormalities in biomarkers of kidney tubular injury, inflammation, fibrosis, secretion, and synthetic function accompany reduced eGFR and albuminuria in type 1 diabetes.

Trial registration number

NCT00360893,NCT00360815.
Estimating the need for inpatient neonatal services: an iterative approach employing evidence and expert consensus to guide local policy in Kenya
Authors: Murphy Georgina A V , Waters Donald , Ouma Paul O , Gathara David , Shepperd Sasha , Snow Robert W , English Mike
Published: November 2017

Universal access to quality newborn health services will be essential to meeting specific Sustainable Development Goals to reduce neonatal and overall child mortality. Data for decision making are crucial for planning services and monitoring progress in these endeavours. However, gaps in local population-level and facility-based data hinder estimation of health service requirements for effective planning in many low-income and middle-income settings.

We worked with local policy makers and experts in Nairobi City County, an area with a population of four million and the highest neonatal mortality rate amongst counties in Kenya, to address this gap, and developed a systematic approach to use available data to support policy and planning. We developed a framework to identify major neonatal conditions likely to require inpatient neonatal care and identified estimates of incidence through literature review and expert consultation, to give an overall estimate for the year 2017 of the need for inpatient neonatal care, taking account of potential comorbidities.

Our estimates suggest that almost 1 in 5 newborns (183/1000 live births) in Nairobi City County may need inpatient care, resulting in an estimated 24 161 newborns expected to require care in 2017. Our approach has been well received by local experts, who showed a willingness to work together and engage in the use of evidence in healthcare planning. The process highlighted the need for co-ordinated thinking on admission policy and referral care especially in a pluralistic provider environment helping build further appetite for data-informed decision making.
EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report
Authors: Bottai Matteo , Tjärnlund Anna , Santoni Giola , Werth Victoria P , Pilkington Clarissa , de Visser Marianne , Alfredsson Lars , Amato Anthony A , Barohn Richard J , Liang Matthew H , Singh Jasvinder A , Aggarwal Rohit , Arnardottir Snjolaug , Chinoy Hector , Cooper Robert G , Danko Katalin , Dimachkie Mazen M , Feldman Brian M , García-De La Torre Ignacio , Gordon Patrick , Hayashi Taichi , Katz James D , Kohsaka Hitoshi , Lachenbruch Peter A , Lang Bianca A , Li Yuhui , Oddis Chester V , Olesinka Marzena , Reed Ann M , Rutkowska-Sak Lidia , Sanner Helga , Selva-O’Callaghan Albert , Wook Song Yeong , Vencovsky Jiri , Ytterberg Steven R , Miller Frederick W , Rider Lisa G , Lundberg Ingrid E
Published: November 2017

Objective

To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.

Methods

An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach.

Results

The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.

Conclusions

The new EULAR/ACR classification criteria provide a patient’s probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.
Case of clinical canine leptospirosis in Uganda
Authors: Alinaitwe Lordrick , Kakooza Steven , Eneku Wilfred , Dreyfus Anou , Rodriguez‐Campos Sabrina
Published: November 2017

In this report, we present the first confirmed case of clinical leptospirosis in a dog in Uganda. A five‐year‐old entire male German shepherd dog from a kennel of 25 guard dogs was admitted to the animal clinic and presented hypothermia, lethargy and jaundice of the mucous membranes. The body temperature remained low during the three days post admission until death. The postmortem examination and histological findings led to suspicion of acute leptospirosis. The diagnosis was confirmed by demonstration of pathogenic Leptospira spp DNA in homogenates of the kidney, liver and lungs by real‐time PCR. This case highlights that accurate diagnostic methods are needed to clarify if clinical leptospirosis is to date underestimated in Uganda and if it has an impact on public health. Awareness should be raised among veterinarians to consider leptospirosis more often as a differential diagnosis as a consequence of the non‐specific signs observed in the presented case.
Universal aqueous synthesis of ultra-small polymer-templated nanoparticles: synthesis optimization methodology for counterion-collapsed poly(acrylic acid)
Authors: Kim Nari , Cheng Calvin C.H. , Goh M. Cynthia
Published: November 2017

A long polyelectrolyte chain collapses into a nano-sized particle upon the addition of counterions under appropriate solution conditions. This phenomenon forms the basis for a simple universal method for aqueous synthesis of ultra-small (<10 nm) metal, metal oxide, and other types of nanoparticles in the following manner: the counterion-collapsed polyelectrolyte chains are made stable by crosslinking, effectively trapping the counterions, which are subsequently chemically modified, to form metal nanoparticles via reduction or metal oxides nanoparticles via oxidation, within the collapsed polymer nanoparticle. This highly versatile platform methodology can be applied to almost any polyelectrolyte–counterion pair, making possible the rapid development of syntheses of different nanoparticles within the same chemical environment. Using poly(acrylic acid) as a model system, a methodology for the optimization of conditions for the polyelectrolyte collapse by various mono- and multi-valent metal cations is developed. The optimal counterion concentration did not correlate with ionic strength and metal ion valency and was highly variable from system to system. By monitoring the polyelectrolyte conformation using viscosity and turbidity measurements, the appropriate metal ion concentration for each nanoparticle system was determined.
Are Wearables Ready for Secure and Direct Internet Communication?
Authors: Kolamunna Harini , Chauhan Jagmohan , Hu Yining , Thilakarathna Kanchana , Perino Diego , Makaroff Dwight , Seneviratne Aruna
Published: November 2017

Recent advances in wearable technology tend towards standalone wearables. Most of today's wearable devices and applications still rely on a paired smartphone for secure Internet communication, even though many current generation wearables are equipped with Wi-Fi and 3G/4G network interfaces that provide direct Internet access. Yet it is not clear if such communication can be efficiently and securely supported through existing protocols. Our findings show that it is possible to use secure and efficient direct communication between wearables and the Internet
Modeling Cancer in the CRISPR Era
Authors: Ventura Andrea , Dow Lukas E.
Published: November 2017

In just a few short years, CRISPR/Cas9 genome editing has fundamentally changed basic, agricultural, and biomedical research, but no field has felt a more profound impact than cancer research. The ability to quickly and precisely manipulate the genome has opened the floodgates for a new and more elaborate understanding of how genes and gene regulation influence disease. Here we review how the development and implementation of CRISPR-based technology is redefining the way we study cancer, and ultimately how it may be used to improve treatment outcomes.
Fast oscillation dynamics during hypsarrhythmia as a localization biomarker
Authors: Kim Min-Jee , Yum Mi-Sun , Yeh Hye-Ryun , Ko Tae-Sung
Published: November 2017

Hypsarrhythmia in West syndrome, although hard to define, is characterized by chaotic and disorganized electrical activity of the brain and is often regarded as a generalized EEG pattern without any localization value. Using event-related spectral perturbation (ERSP), we tried to determine the brain dynamics during hypsarrhythmia. Routine 1-h scalp EEGs were retrieved from 31 patients with infantile spasms and 20 age-matched controls. Using the EEGLAB toolbox of MATLAB 2015b, the ERSPs of fast oscillations (FOs; 20–100 Hz) of selected channels were analyzed and compared among groups according to their MRI lesions. FO-ERSP cutoff values for predicting the pathologic foci were estimated. The mean FO-ERSPs across all analyzed electrodes of patients with spasms were significantly higher than those of controls. When the patients were categorized into nonlesional, focal/multifocal, or diffuse lesional groups, the FO-ERSP of patients in the focal/multifocal lesional group was significantly lower than that of those in the nonfocal or diffuse lesional groups. In the focal/multifocal lesional group, seven patients (7/9, 77.8%) showed that the locations of channels with high FO-ERSPs were matched to the pathologic MRI lesions. Thus, the localization of high FO-ERSPs is closely associated with the location of pathologic brain lesions. Further research is required to prove the value of the FO-ERSP as an important quantitative localizing biomarker of West syndrome.

NEW & NOTEWORTHY The locations of high fast oscillation-event-related spectral perturbations (FO-ERSPs) are closely associated with brain pathologic lesions, and high FO-ERSPs can be used as a localization biomarker of pathologic brain lesions in patients with hypsarrhythmia. With further validation, FO-ERSP might be useful as a biomarker for the localization of hidden pathologies in conditions with generalized epileptiform activities such as West syndrome.
Abnormal visual gain control and excitotoxicity in early-onset Parkinson’s disease Drosophila models
Authors: Himmelberg Marc M. , West Ryan J. H. , Elliott Christopher J. H. , Wade Alex R.
Published: November 2017

The excitotoxic theory of Parkinson’s disease (PD) hypothesizes that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD (EOPD) Drosophila models DJ-1αΔ 72, DJ-1βΔ 93, and PINK15. We used an electroretinogram to record steady-state visually evoked potentials driven by temporal contrast stimuli. At 1 day of age, all EOPD mutants had a twofold increase in response amplitudes compared with w̄ controls. Furthermore, we found that excitotoxicity occurs in older EOPD models after increased neural activity is triggered by visual stimulation. In an additional analysis, we used a linear discriminant analysis to test whether there were subtle variations in neural gain control that could be used to classify Drosophila into their correct age and genotype. The discriminant analysis was highly accurate, classifying Drosophila into their correct genotypic class at all age groups at 50–70% accuracy (20% chance baseline). Differences in cellular processes link to subtle alterations in neural network operation in young flies, all of which lead to the same pathogenic outcome. Our data are the first to quantify abnormal gain control and excitotoxicity in EOPD Drosophila mutants. We conclude that EOPD mutations may be linked to more sensitive neuronal signaling in prodromal animals that may cause the expression of PD symptomologies later in life.

NEW & NOTEWORTHY Steady-state visually evoked potential response amplitudes to multivariate temporal contrast stimuli were recorded in early-onset PD Drosophila models. Our data indicate that abnormal gain control and a subsequent visual loss occur in these PD mutants, supporting a broader excitotoxicity hypothesis in genetic PD. Furthermore, linear discriminant analysis could accurately classify Drosophila into their correct genotype at different ages throughout their lifespan. Our results suggest increased neural signaling in prodromal PD patients.
Exposure to Workplace Bullying: The Role of Coping Strategies in Dealing with Work Stressors
Authors: Van den Brande Whitney , Baillien Elfi , Vander Elst Tinne , De Witte Hans , Van den Broeck Anja , Godderis Lode
Published: November 2017

Studies investigating both work- and individual-related antecedents of workplace bullying are scarce. In reply, this study investigated the interaction between workload, job insecurity, role conflict, and role ambiguity (i.e., work-related antecedents), and problem- and emotion-focused coping strategies (i.e., individual-related antecedents) in association with exposure to workplace bullying. Problem-focused coping strategies were hypothesised to decrease (i.e., buffer) the associations between workload, job insecurity, role conflict, and role ambiguity and exposure to bullying, while emotion-focused coping strategies were hypothesised to increase (i.e., amplify) these associations. Results for a heterogeneous sample (N= 3,105) did not provide evidence for problem-focused coping strategies as moderators. As expected, some emotion-focused coping strategies amplified the associations between work-related antecedents and bullying: employees using “focus on and venting of emotions” or “behavioural disengagement” in dealing with job insecurity, role conflict, or role ambiguity were more likely to be exposed to bullying. Similarly, “seeking social support for emotional reasons” and “mental disengagement” amplified the associations of role ambiguity and the associations of both role conflict and role ambiguity, respectively. To prevent bullying, organisations may train employees in tempering emotion-focused coping strategies, especially when experiencing job insecurity, role conflict, or role ambiguity.
Effects of Equipment-Structure-Soil Interaction on Seismic Response of Equipment and Structure via Real-Time Dynamic Substructuring Shaking Table Testing
Authors: Zhang Chongxiang , Jiang Nan
Published: November 2017

Equation of motion for an equipment-structure-soil (ESS) interaction system was derived using the branch substructure method. After rearrangement, this equation was applied to real-time dynamic substructuring shaking table (RTDSST) testing of the ESS system. This method adopts the equipment-structure (ES) subsystem as the experimental substructure and a modal reduced soil model as the numerical substructure: the former is tested via the shaking table, and the latter is numerically simulated, while real-time data communication occurs between the two substructures during testing. A scale model of the ESS system was designed and underwent an RTDSST test. The experimental data were found to be consistent with the numerical calculation results, which corroborates the reliability and validity of the proposed testing method. A comparison of the experimental results from different earthquake stages implies that seismic responses of the equipment and structure decreased in general due to the intervention of soil, but the soil effect weakened with earthquake intensity.
Households’ Preference for Local Rice in the Upper East Region, Ghana
Authors: Sedem Ehiakpor Dennis , Apumbora Justice , Danso-Abbeam Gideon , Adzawla William
Published: November 2017

Considering the increasing demand in the rice industry, the study was undertaken to determine the factors influencing household preference for locally produced rice in the Upper East Region, Ghana. Primary data was obtained from a sample of 180 households with the aid of a structured questionnaire. Probit model and Kendall’s coefficient of concordance were used to analyze the data. Significant socioeconomic factors include income, age, sex, and marital status, whereas the quality factors such as the absence of foreign materials, packaging, and aroma were also significant determinants of preference for local rice. The top three traits consumers consider in their choice for local rice were good-looking grains, excellent packaging, and absence of foreign materials in the rice. There was an evidence of an increased preference for quality local rice. Hence, increased investment in the rice value chain, particularly the processing stage where quality standards remain the topmost priority, will help boost consumers’ confidence in the local rice market.
Secular Changes of Adiposity in Czech Children Aged from 3 to 6 Years: Latent Obesity in Preschool Age
Authors: Sedlak Petr , Pařízková Jana , Procházková Lucie , Cvrčková Lucie , Dvořáková Hana
Published: November 2017

BMI, skinfold thickness, and circumferential measures were assessed in groups of normal healthy Czech boys (n=1764) and girls (n=1762) 3–6 years of age in the late 1950s and 1960s (sample C), in the 1990s (sample B), and in 2014–2016 (sample A). During these decades BMI has not changed significantly, and in selected groups (boys 3, 5, and 6, girls 3 and 6 years) it was most recently found to be significantly lower (P≤0.05). Subscapular, suprailiac, triceps, midthigh, and above patella skinfold thicknesses significantly increased in sample A as compared to sample C (P≤0.001). Comparison of the same skinfolds measured in the nineties (sample B) and more recently (sample A) showed similar increase of subcutaneous fat (P≤0.001). The increase of adiposity characterized by skinfolds occurring in spite of not markedly changed BMI indicates significant changes of body composition—latent (also hidden) obesity. The increase of adiposity was relatively greatest on the trunk (P≤0.001)—which is considered a marker of the greatest health risk. The decrease of femoral circumference (P≤0.05) along with simultaneous increase of thigh skinfold (P≤0.01) revealed the decrease of muscle mass in the lower extremity, obviously due to the reduction of weight-transferring physical activity.
Source and Ecological Risk Characteristics of PAHs in Sediments from Qinhuai River and Xuanwu Lake, Nanjing, China
Authors: Zhao Zhenhua , Qin Zhirui , Cao JingJing , Xia Liling
Published: November 2017

In order to investigate the residual characteristics, sources, and ecological risk of PAHs in sediment from urban rivers, the sediments of 15 typical sites from Qinhuai River and Xuanwu Lake, which are typical urban rivers and lake, were collected from October 2015 to July 2016; the sources of PAHs in sediment were also identified by several methods. Results showed that ∑PAHs concentration in sediment ranged from 796.2 ng/g to 10,470 ng/g with an average of 2,713.8 ng/g. High molecular weight PAHs with 4-5 rings were most prominent in the sediment during all four seasons. Source characterization studies based on the analysis of diagnostic ratio (triangular plot method), cluster analysis, and positive factor matrix analysis suggested that the PAHs of Qinhuai River Basin were mainly from pyrogenic origin (biomass and coal combustion and vehicular emission), and the petroleum source also cannot be ignored (specially in summer). Most individual PAHs occasionally affect the aquatic organisms. The highest benzo[a]pyrene-equivalent doses (BaPeq dose) appear at the sites of sewage discharge and heavy traffic. So, the PAHs pollution sources of urban water body have obvious seasonal-dependent and human activities-dependent characteristics.
Q Fever Presented as a Large Retroperitoneal Pseudotumoral Mass
Authors: Nowroozizadeh Behdokht , Haghighi Mehmandari Negar , Gallegos Nicolas , Perez-Rosendahl Mari , Lu Di
Published: November 2017

Background. Q fever is an infection caused by Coxiella burnetii, an intracellular organism. Acute infection is most often a benign and asymptomatic process; however, some individuals may go on to develop subacute and persistent localized symptomatic Q fever. As such, the clinical and histopathologic findings of Q fever are widely variable and may be missed if clinical suspicion is not high. Case Presentation. Herein we report the first case of C. burnetii infection presenting as an isolated retroperitoneal mass. A 61-year-old male underwent axillary-bifemoral bypass surgery. His postoperative course was complicated by the discovery of a large retroperitoneal mass. Conclusion. Clinical and histopathologic findings of Coxiella burnetii infection are variable and can be deceiving. These are often nonspecific, especially in its persistent localized infectious stages.
CD60b: Enriching Neural Stem/Progenitor Cells from Rat Development into Adulthood
Authors: Gubert Fernanda , Zaverucha-do-Valle Camila , Furtado Michelle , Pimentel-Coelho Pedro M. , Mortari Nicoli , Leão Ana C. M. , Hayashi Elize A. , Nobrega Alberto , Mendez-Otero Rosalia , Santiago Marcelo F.
Published: November 2017

CD60b antigens are highly expressed during development in the rat nervous system, while in the adult their expression is restricted to a few regions, including the subventricular zone (SVZ) around the lateral ventricles—a neurogenic niche in the adult brain. For this reason, we investigated whether the expression of C60b is associated with neural stem/progenitor cells in the SVZ, from development into adulthood. We performedin vitroandin vivoanalyses of CD60b expression at different stages and identified the presence of these antigens in neural stem/progenitor cells. We also observed that CD60b could be used to purify and enrich a population of neurosphere-forming cells from the developing and adult brain. We showed that CD60b antigens (mainly corresponding to ganglioside 9-O-acetyl GD3, a well-known molecule expressed during central nervous system development and mainly associated with neuronal migration) are also present in less mature cells and could be used to identify and isolate neural stem/progenitor cells during development and in the adult brain. A better understanding of molecules associated with neurogenesis may contribute not only to improve the knowledge about the physiology of the mammalian central nervous system, but also to find new treatments for regenerating tissue after disease or brain injury.
Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells
Authors: Mellado-López Maravillas , Griffeth Richard J. , Meseguer-Ripolles Jose , Cugat Ramón , García Montserrat , Moreno-Manzano Victoria
Published: November 2017

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.
Connections between Certain Subclasses of Analytic Univalent Functions Based on Operators
Authors: Ezhilarasi R. , Sudharsan T. V. , Haji Mohd Maisarah , Subramanian K. G.
Published: November 2017

In this paper, by applying the Hohlov linear operator, connections between the class SD(α),  α≥0, and two subclasses of the class A of normalized analytic functions are established. Also an integral operator related to hypergeometric function is considered.
Sirolimus Ointment for Facial Angiofibromas in Individuals with Tuberous Sclerosis Complex
Authors: Amin S. , Lux A. , Khan A. , O’Callaghan F.
Published: November 2017

Background. Facial angiofibromas affect most patients with tuberous sclerosis complex. They tend to progress, can cause recurrent bleeding and facial disfigurement, and have significant psychological effects. We reviewed the effectiveness and safety of topical sirolimus ointment 0.1%. We also assessed the effect of treatment on quality of life. Methods. We report our experience in using sirolimus ointment in 14 patients with TSC (9 children and 5 adults). The impact of sirolimus ointment was monitored with digital photography, dermatological review using a validated Facial Angiofibroma Severity Index (FASI), and quality of life assessments using the questionnaires PedsQL for children and SF36 for adults. Results. The FASI scores were improved in 12/14 cases after six months’ treatment, and improvement was more likely in children (median FASI scores of improvement after treatment were 3 points for children and 1 for adults). Proxy-reported PedsQL scores for the total psychosocial domain improved significantly in the children in the cohort with treatment. Conclusions. Sirolimus ointment 0.1% administered once a day was effective in treating facial angiofibromas. It appears to be safe and well tolerated and to have a positive impact on patients’ quality of life. It appeared to be most beneficial when started in childhood.
Description and Validation of TAVIApp: A Novel Mobile Application for Support of Physicians in the Management of Aortic Stenosis—Management of Aortic Stenosis with TAVIApp
Authors: Indolfi Ciro , Sabatino Jolanda , De Rosa Salvatore , Mongiardo Annalisa , Ricci Pietrantonio , Spaccarotella Carmen
Published: November 2017

Background. Aortic stenosis (AS) is the most common heart valve disease in developed countries. The advent of transcatheter aortic valve implantation (TAVI) significantly improved patients’ outcome but made clinical management more complex. The aim of the present study was to describe TAVIApp, a mobile app we developed to guide the management of AS, and test its efficacy. Methods and Results. Clinical cases comprising 42 patients with AS were blindly evaluated by (A) an interventional cardiologist, assisted by the Heart Team (EXPERT), (B) young residents in cardiology, and (C) a young resident supported by TAVIApp. There was poor concordance between Group A and Group B with low performance by young residents (k=0.52; p<0.001). However, concordance increased to an optimal value when young residents were supported by TAVIApp (k=1.0; p<0.001) for the diagnosis of severe AS and eligibility assessment. Furthermore, regarding the selection of the most appropriate prosthesis size, concordance to Group A was poor without TAVIApp support (Group B) (k=0.78; p=0.430), but excellent with TAVIApp (k=1.0; p<0.001). Conclusions. This study is the first describing and validating a new mobile application to support the management of AS. TAVIApp supports cardiologists in the evaluation of stenosis severity, eligibility for TAVI or AVR, and selection of the most appropriate prosthesis size in individual patients.
Atypical G Protein β5 Promotes Cardiac Oxidative Stress, Apoptosis, and Fibrotic Remodeling in Response to Multiple Cancer Chemotherapeutics
Authors: Chakraborti Sreemoyee , Pramanick Arnab , Saha Sudipta , Roy Somnath Singha , Chaudhuri Arnab Ray , Das Madhusudan , Ghosh Sujoy , Stewart Adele , Maity Biswanath
Published: November 2017

The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. Though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium correlating with oxidative stress, myocyte apoptosis, and the accumulation of proinflammatory and profibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII proapoptotic signaling cascades. In addition, Gβ5 loss allowed for maintenance of Δψm, basal mitochondrial calcium uniporter expression, and mitochondrial Ca2+ levels, effects likely to preserve functional myocyte excitation–contraction coupling. The deleterious effects of Gβ5 are not restricted to VCM, however, as Gβ5 knockdown also reduces chemotherapy-induced release of proinflammatory cytokines (e.g., TNFα), hypertrophic factors (e.g., ANP), and profibrotic factors (e.g., TGFβ1) from both VCM and ventricular cardiac fibroblasts, with the most dramatic reduction occurring in cocultured cells. Our experiments suggest that Gβ5 facilitates the myofibroblast transition, the persistence of which contributes to pathologic remodeling and heart failure. The convergence of Gβ5-mediated, ROS-dependent signaling pathways in both cell types represents a critical etiological factor in the pathogenesis of chemotherapy-induced cardiotoxicity. Indeed, intracardiac injection of Gβ5-targeted shRNA allowed for heart-specific protection against the damaging impact of chronic chemotherapy. Together, our results suggest that inhibition of Gβ5 might represent a novel means to circumvent cardiotoxicity in cancer patients whose treatment regimens include anthracyclines, taxanes, or fluoropyrimidines.

Significance: These findings suggest that inhibiting an atypical G-protein might provide a strategy to limit the cardiotoxicity in cancer patients treated with anthracyclines, taxanes, or fluoropyrimidines. Cancer Res; 78(2); 528–41. ©2017 AACR.
MYC Overexpression at the Protein and mRNA Level and Cancer Outcomes among Men Treated with Radical Prostatectomy for Prostate Cancer
Authors: Pettersson Andreas , Gerke Travis , Penney Kathryn L. , Lis Rosina T. , Stack Edward C. , Pértega-Gomes Nelma , Zadra Giorgia , Tyekucheva Svitlana , Giovannucci Edward L. , Mucci Lorelei A. , Loda Massimo
Published: November 2017

Background: The proto-oncogene MYC is implicated in prostate cancer progression. Whether MYC tumor expression at the protein or mRNA level is associated with poorer prognosis has not been well studied.

Methods: We conducted a cohort study including 634 men from the Physicians' Health Study and Health Professionals Follow-up Study treated with radical prostatectomy for prostate cancer in 1983–2004 and followed up for a median of 13.7 years. MYC protein expression was evaluated using IHC, and we used Cox regression to calculate HRs and 95% confidence intervals (CIs) of its association with lethal prostate cancer (distant metastases/prostate cancer–related death). We assessed the association between MYC mRNA expression and lethal prostate cancer in a case–control study, including 113 lethal cases and 291 indolent controls.

Results: MYC nuclear protein expression was present in 97% of tumors. MYC protein expression was positively correlated with tumor proliferation rate (r = 0.37; P < 0.001) and negatively correlated with apoptotic count (r = −0.17; P < 0.001). There were no significant associations between MYC protein expression and stage, grade, or PSA level at diagnosis. The multivariable HR for lethal prostate cancer among men in the top versus bottom quartile of MYC protein expression was 1.09 (95% CI, 0.50–2.35). There was no significant association between MYC mRNA expression and lethal prostate cancer.

Conclusions: Neither MYC protein overexpression nor MYC mRNA overexpression are strong prognostic markers in men treated with radical prostatectomy for prostate cancer.

Impact: This is the largest study to examine the prognostic role of MYC protein and mRNA expression in prostate cancer. Cancer Epidemiol Biomarkers Prev; 27(2); 201–7. ©2017 AACR.
Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium
Authors: Harris Holly R. , Babic Ana , Webb Penelope M. , Nagle Christina M. , Jordan Susan J. , Risch Harvey A. , Rossing Mary Anne , Doherty Jennifer A. , Goodman Marc T. , Modugno Francesmary , Ness Roberta B. , Moysich Kirsten B. , Kjær Susanne K. , Høgdall Estrid , Jensen Allan , Schildkraut Joellen M. , Berchuck Andrew , Cramer Daniel W. , Bandera Elisa V. , Wentzensen Nicolas , Kotsopoulos Joanne , Narod Steven A. , Phelan Catherine M. , McLaughlin John R. , Anton-Culver Hoda , Ziogas Argyrios , Pearce Celeste L. , Wu Anna H. , Terry Kathryn L.
Published: November 2017

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies.

Methods: We analyzed data from 14 case–control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression.

Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58–0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76–0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65–1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001).

Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype.

Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174–82. ©2017 AACR.
The Effects of Resistance Exercise on Biomarkers of Breast Cancer Prognosis: A Pooled Analysis of Three Randomized Trials
Authors: Winters-Stone Kerri M. , Wood Lisa J. , Stoyles Sydnee , Dieckmann Nathan F.
Published: November 2017

Background: Using a secondary data analysis from randomized controlled trials comparing one year of resistance exercise (n = 109) to a placebo control condition (n = 106) in postmenopausal, posttreatment breast cancer survivors, we investigated the influence of resistance training and changes in body composition on markers associated with cancer progression.

Methods: Measures included serum levels of insulin, IGF-1, IGFBP1-3, leptin, serum amyloid A (SAA), adiponectin, C-reactive protein (CRP), IL1β, TNFα, IL6, and IL8, and body composition (total, lean and fat mass in kg) by DXA at baseline, 6, and 12 months. Linear mixed effects models were used to examine the association between group, biomarkers, and body composition and whether or not changes in muscle strength or body composition influenced the effect of exercise on biomarkers.

Results: CRP decreased over time among women participating in resistance training compared with increases in controls (P = 0.045). In stratified analyses and compared with increases in controls, women who gained strength reduced CRP (P = 0.003) and maintained levels of IL1β and IL6. Among exercisers who lost weight (≥2 kg), CRP (P = 0.045), leptin (P < 0.01), and SAA (P = 0.029) decreased, whereas IGF-BP1 (P = 0.036) increased compared with controls.

Conclusions: Resistance training may lower inflammation and improve insulin pathway profiles, but the magnitude and degree of benefit from exercise may depend upon whether or not women gained strength, a possible marker of compliance with training, and/or lost weight during exercise.

Impact: Future resistance training trials should consider these potential influencing factors as they may determine how well exercise can slow cancer progression and prevent disease recurrence. Cancer Epidemiol Biomarkers Prev; 27(2); 146–53. ©2017 AACR.
Connections of Anterior Thalamic Visual Centers in the Leopard Frog, Rana pipiens
Authors: Recktenwald Eric W. , Dudkin Elizabeth A. , Skorina Laura K. , Saidel William M. , Gruberg Edward R.
Published: November 2017

The amphibian retina projects to two discrete regions of neuropil in the anterior thalamus: the neuropil of Bellonci and the corpus geniculatum. These retinorecipient areas are encompassed within a larger zone of surrounding neuropil we call the NCZ (for neuropil of Bellonci/corpus geniculatum zone). The NCZ is characterized electrophysiologically by a distinctive tonic oscillatory response to blue light; it appears to be a visual module involved in processing the stationary visual environment. Using horseradish peroxidase (HRP), we mapped the connections of the NCZ. Retrogradely labeled cell bodies are found in: (1) the contralateral anterior thalamus; (2) both retinas; and (3) the posterior medial dorsal thalamus (PMDT). Anterogradely labeled fibers are found in: (1) the contralateral anterior thalamus; (2) the ipsilateral PMDT; (3) the ipsilateral neuropil lateral to the posterior tuberculum in the ventrolateral posterior thalamus; and (4) the ipsilateral anterior medulla. There are no direct connections between the NCZ and the telencephalon, the tectum, or the suprachiasmatic nucleus. Applying HRP to the PMDT, we found that its inputs are limited to the contralateral and ipsilateral NCZ and the contralateral PMDT. Thus, PMDT appears to be a satellite of the NCZ. Blue light elicits tonic oscillatory electrical responses in the PMDT quite similar to the responses to blue light in the NCZ. We discuss how the leopard frog NCZ and the mammalian ventral lateral geniculate nucleus share anatomical and physiological properties.
A Retrospective Study Comparing K101 Nail Solution as a Monotherapy and in Combination with Oral Terbinafine or Itraconazole for the Treatment of Toenail Onychomycosis
Authors: Shemer Avner , Gupta Aditya K. , Babaev Meir , Barzilai Aviv , Farhi Renata , Daniel III C. Ralph
Published: November 2017

Background: Onychomycosis is a difficult-to-treat fungal infection of the nails. The efficacy of monotherapy is not ideal, and combination therapies provide an alternative that may increase treatment efficacy. Method: A retrospective analysis of data from 91 patients was undertaken. Treatment for toenail onychomycosis occurred between 2014 and 2016 and consisted of combination therapy with oral terbinafine (250 mg/day for 12 weeks) or itraconazole (3 pulses, 400 mg/day for 7 days) + K101 nail solution daily, or K101 nail solution monotherapy. Efficacy outcomes at 12 and 15 months were analyzed. Results: At 12 months, the clinical cure rate for combination of terbinafine + K101 solution was significantly higher than that for K101 monotherapy (p = 0.008). Patients receiving this combination also showed significant improvement in percent of affected nail at 3 months (p = 0.029), while patients receiving itraconazole + K101 solution demonstrated improvement in percent of affected nail at 6 months (p = 0.037). At 15 months, there was no significant difference between treatments for complete, clinical, and mycological cure. Conclusion: Combination therapy with oral terbinafine or itraconazole and K101 nail solution results in clearance of infected nail earlier than that with topical K101 alone. These combinations may encourage compliance and be effective for patients with moderate onychomycosis.
From the Judaean Desert to the Great Sea: Qumran in a Mediterranean Context
Authors: Mizzi Dennis
Published: November 2017

The time when Qumran was studied in splendid isolation is long gone, but much work remains to be done when it comes to situating the site in its wider context. In this paper, Qumran is contextualized, on the one hand, within the larger ecological history of the Mediterranean and, on the other, within the Mediterranean world of classical antiquity. Questions regarding the functions of the Qumran settlement are addressed from the perspective of “marginal zones” in the Mediterranean, which provides an ideal backdrop through which to illumine aspects of daily life at Qumran. Furthermore, it is shown how comparative case studies from the Graeco-Roman Mediterranean help us to nuance the discussion concerning “Hellenization” or “Romanization” with regard to Qumran. Finally, a new understanding of L4, which is here interpreted primarily as a dining room, is proposed on the basis of archaeological parallels from the Graeco-Roman world. A pan-Mediterranean perspective, therefore, allows us to generate new insights on old questions and novel interpretations.
Louis Lamm (1871–1943): A Short Biography of a Dedicated Judaica Publisher and Bookseller
Authors: Freudenthal Gad
Published: November 2017

Louis Lamm was a famed bookseller and publisher of Judaica in Berlin and Amsterdam during the four decades preceding his assassination in 1943. Yet even Internet fails to provide elementary biographical details about his life and work. The aim of this short paper is to partially fill this lacuna and contribute to the perpetuation of the memory of a dedicated lover of Jewish books.