bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of L4 lymph node dissection on long-term survival in left-side operable non-small-cell lung cancer: a propensity score matching study
Authors: Yang Mu-Zi , Hou Xue , Li Ji-Bin , Cai Jing-Sheng , Yang Jie , Li Shuo , Long Hao , Fu Jian-Hua , Zhang Lan-Jun , Lin Peng , Rong Tie-Hua , Yang Hao-Xian
Published: January 2020

OBJECTIVES

We investigated the impact of level 4 (L4) lymph node dissection (LND) on overall survival (OS) in left-side resectable non-small-cell lung cancer (NSCLC), with the aim of guiding lymphadenectomy.

METHODS

A total of 1929 patients with left-side NSCLC who underwent R0 resection between 2001 and 2014 were included in the study. The patients were divided into a group with L4 LND (L4 LND+) and a group without L4 LND (L4 LND−). Propensity score matching was applied to minimize selection bias. The Kaplan–Meier method and Cox proportional hazards model were used to assess the impact of L4 LND on OS.

RESULTS

A total of 317 pairs were matched. Of the cohort of patients, 20.3% (391/1929) had L4 LND. Of these patients, 11.8% (46/391) presented with L4 lymph node metastasis. L4 lymph node metastasis was not associated with the primary tumour lobes (P = 0.61). Before propensity score matching, the 5-year OS was comparable between the L4 LND+ and L4 LND− groups (69.0% vs 65.2%, P = 0.091). However, after propensity score matching, the 5-year OS of the L4 LND+ group was much improved compared to that of the L4 LND− group (72.9% vs 62.3%, P = 0.002) and L4 LND was an independent factor favouring OS (hazard ratio 0.678, 95% confidence interval 0.513–0.897; P = 0.006). Subgroup analysis suggested that L4 LND was an independent factor favouring OS in left upper lobe tumours.

CONCLUSIONS

In patients with left-side operable NSCLC, L4 lymph node metastasis was not rare and L4 LND should be routinely performed.
Human iPSC-derived Down syndrome astrocytes display genome-wide perturbations in gene expression, an altered adhesion profile, and increased cellular dynamics
Authors: Ponroy Bally Blandine , Farmer W Todd , Jones Emma V , Jessa Selin , Kacerovsky J Benjamin , Mayran Alexandre , Peng Huashan , Lefebvre Julie L , Drouin Jacques , Hayer Arnold , Ernst Carl , Murai Keith K
Published: January 2020

Down syndrome (DS), caused by the triplication of human chromosome 21, leads to significant alterations in brain development and is a major genetic cause of intellectual disability. While much is known about changes to neurons in DS, the effects of trisomy 21 on non-neuronal cells such as astrocytes are poorly understood. Astrocytes are critical for brain development and function, and their alteration may contribute to DS pathophysiology. To better understand the impact of trisomy 21 on astrocytes, we performed RNA-sequencing on astrocytes from newly produced DS human induced pluripotent stem cells (hiPSCs). While chromosome 21 genes were upregulated in DS astrocytes, we found consistent up- and down-regulation of genes across the genome with a strong dysregulation of neurodevelopmental, cell adhesion and extracellular matrix molecules. ATAC (assay for transposase-accessible chromatin)-seq also revealed a global alteration in chromatin state in DS astrocytes, showing modified chromatin accessibility at promoters of cell adhesion and extracellular matrix genes. Along with these transcriptomic and epigenomic changes, DS astrocytes displayed perturbations in cell size and cell spreading as well as modifications to cell-cell and cell-substrate recognition/adhesion, and increases in cellular motility and dynamics. Thus, triplication of chromosome 21 is associated with genome-wide transcriptional, epigenomic and functional alterations in astrocytes that may contribute to altered brain development and function in DS.
Disruption of a RAC1-centred network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration
Authors: Kikuchi Masataka , Sekiya Michiko , Hara Norikazu , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi , Iijima Koichi M , Nakaya Akihiro
Published: January 2020

The molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, including Rac1, as key players in PDN collapse. Using publicly available as well as our own gene expression data, we confirmed that the mRNA expression level of the RAC1 gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilized Drosophila as a genetic model and found that modest knockdown of Rac1 in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator of RAC1 in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were increased specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y caused RAC1 downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.
A Family of Riesz Distributions for Differential Forms on Euclidian Space
Authors: Fischmann Matthias , Ørsted Bent
Published: January 2020

In this paper, we introduce a new family of operator-valued distributions on Euclidian space acting by convolution on differential forms. It provides a natural generalization of the important Riesz distributions acting on functions, where the corresponding operators are $(-\Delta )^{-\alpha /2}$, and we develop basic analogous properties with respect to meromorphic continuation, residues, Fourier transforms, and relations to conformal geometry and representations of the conformal group.
Results of the Italian infection-Carbapenem Resistance Evaluation Surveillance Trial (iCREST-IT): activity of ceftazidime/avibactam against Enterobacterales isolated from urine
Authors: Giani Tommaso , Antonelli Alberto , Sennati Samanta , Di Pilato Vincenzo , Chiarelli Adriana , Cannatelli Antonio , Gatsch Christopher , Luzzaro Francesco , Spanu Teresa , Stefani Stefania , Rossolini Gian Maria
Published: January 2020

Objectives

To assess the in vitro antibacterial activity of ceftazidime/avibactam against a recent Italian collection of carbapenem-resistant Enterobacterales (CRE) isolated from urine specimens.

Methods

Consecutive Gram-negative isolates from urine specimens, collected from inpatients in five Italian hospitals during the period October 2016 to February 2017, were screened for CRE phenotype using chromogenic selective medium and identified using MALDI-TOF MS. Antimicrobial susceptibility testing was performed by reference broth microdilution (BMD) and, for ceftazidime/avibactam, also by Etest® CZA. Results were interpreted according to the EUCAST breakpoints. All confirmed CRE were subjected to real-time PCR targeting blaKPC-type, blaVIM-type, blaNDM-type and blaOXA-48-type carbapenemase genes. Non-MBL-producing isolates resistant to ceftazidime/avibactam were subjected to WGS and their resistome and clonality were analysed.

Results

Overall, 318 non-replicate presumptive CRE were collected following screening of 9405 isolates of Enterobacterales (3.4%) on chromogenic selective medium. Molecular analysis revealed that 216 isolates were positive for a carbapenemase gene (of which 92.1%, 2.8%, 1.4% and 1.4% were positive for blaKPC-type, blaOXA-48-type, blaNDM-type and blaVIM-type, respectively). Against the confirmed carbapenemase-producing Enterobacterales (CPE), ceftazidime/avibactam was the most active compound, followed by colistin (susceptibility rates 91.6% and 69.4%, respectively). Compared with BMD, Etest® for ceftazidime/avibactam yielded consistent results (100% category agreement). All class B β-lactamase producers were resistant to ceftazidime/avibactam, while OXA-48 and KPC producers were susceptible, with the exception of seven KPC-producing isolates (4.2%). The latter exhibited an MIC of 16 to >32 mg/L, belonged to ST512, produced KPC-3 and showed alterations in the OmpK35 and Ompk36 porins.

Conclusions

Ceftazidime/avibactam showed potent in vitro activity against a recent Italian collection of CPE from urine.
A Green HPLC Method for Determination of Nine Sulfonamides in Milk and Beef, and Its Greenness Assessment with Analytical Eco-Scale and Greenness Profile
Authors: Duan Xiaoyun , Liu Xiaofeng , Dong Yue , Yang Jing , Zhang Jing , He Shujuan , Yang Fatang , Wang Zhen , Dong Yuming
Published: January 2020

Background

Sulfonamides have been widely used in the prevention and clinical treatment of bacterial diseases in livestock and poultry. The use of sulfonamides increases the risk of veterinary drug residues in animal derived foods. The traditional reversed phase liquid chromatography methods for sulfonamides residues detection in animal derived foods have the problem of high consumption of organic solvents.

Objective

The aim of this study was to establish a green high-performance liquid chromatography method for the detection of sulfonamides residues in different animal-origin foods.

Method

The sample extraction solutions were purified by the Agela Cleanert PEP-2 cartridge and analyzed by the high-performance liquid chromatography method using ethanol as the green alternative solvent.

Results

The proposed method was validated in terms of linear range (20–1000 μg/kg), limit of detection (3.0–12.3 μg/kg), limit of quantitation (10–43 μg/kg), accuracy (80.7–101.3%), and repeatability and reproducibility (RSD <5.9% and RSD <8.5% respectively).

Conclusions

The proposed method is an environmentally friendly, sensitive and reliable high-performance liquid chromatography method for simultaneous determination of sulfonamide residues in animal-origin foods.

Highlights

In this work, we firstly developed a green high-performance liquid chromatography method for simultaneous determination of the residues of nine sulfonamides in milk and beef with ethanol as the green alternative solvent.
Embryological development of the freshwater crab Esanthelphusa nani (Naiyanetr, 1984) (Brachyura: Gecarcinucidae) using confocal laser scanning microscopy
Authors: Maneein Rachata , Martinand-Mari Camille , Claude Julien , Kitana Jirarach , Kitana Noppadon
Published: January 2020

We investigated the embryological development of Esanthelphusa nani (Naiyanetr, 1984), a common rice-field crab in northern Thailand, using confocal laser scanning microscopy. The development of E. nani can be completed in eggs within 12 d resulting in a hatchling stage corresponding to the megalopa stage. Pre-organogenetic stages were characterized by a superficial cleavage, including egg cleavage, egg blastula, and egg gastrula. Organogenesis stages were identified by the appearances of appendages and was divided into egg nauplius, egg zoea, and egg megalopa. Crabs metamorphose to juveniles after hatching. By providing new comparative data, our study shed some new light on the relationship between environment, phylogeny, and development, opening a potential area of research from the perspective of ecological, evolutionary, and developmental biology.
Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns
Authors: Rivera Donna R , Grothen Andrew , Ohm Bradley , McNeel Timothy S , Brennan Sean , Lam Clara J K , Penberthy Lynne , Enewold Lindsey , Petkov Valentina I
Published: January 2020

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED-National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immunotherapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I–IIIA (20 701) and stage IIIB–IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promoting more standardized and efficient treatment-related cancer research.
Supplying Allies: Political Economy of Coalition Warfare
Authors: Cappella Zielinski Rosella , Poast Paul
Published: January 2020

We outline a framework for understanding variation in cobelligerent resource coordination of money and material. An important feature of coalitional resource procurement is the role played by private firms and market forces. These shape the processes by which cobelligerents facilitate acquisition and distribution. At times, cobelligerents rely on themselves or the unilateral provision of resources from a major power supplier. At other times, cobelligerents pool their resources and create international institutions to coordinate the purchase of material. Our framework demonstrates that to understand the means by which coalitions supply themselves and, in turn, create wartime efficiencies in money and material, one must account for both classic determinants of alliance politics—namely the distribution of power between allies—as well as domestic and transnational market forces that can constrain or enable coalition members’ ability, individually and collectively, to procure war inputs.
Conditional Convergence and the Rise of China: A Political Economy Approach to Understanding Global Power Transitions
Authors: Beckley Michael
Published: January 2020

Many scholars predict that China will soon challenge the United States for global primacy. This prediction is largely based on power transition theory, which assumes that rising challengers inevitably “converge” economically and militarily with reigning hegemons. Economists, however, have shown that convergence is a conditional process: sometimes poor countries grow faster than rich countries, but sometimes they fall further behind. Determining whether a US-China power transition will occur in the years ahead, therefore, requires specifying the drivers of long-term economic growth and assessing each country's growth prospects in light of these factors. This article does exactly that. Drawing on recent research in economics, I show that there are three main growth drivers—geography, institutions, and demography—and that the United States scores highly across these factors whereas China suffers from critical weaknesses. These results suggest that a US-China power transition is unlikely.
Faculty Assessments in a Military Medical Field Practicum: Rater Experience and Gender Do Not Appear to Influence Scoring
Authors: Barry Erin S , Dong Ting , Durning Steven J , Schreiber-Gregory Deanna , Torre Dario , Grunberg Neil E
Published: January 2020

Introduction

Any implicit and explicit biases that exist may alter our interpretation of people and events. Within the context of assessment, it is important to determine if biases exist and to decrease any existing biases, especially when rating student performance to provide meaningful, fair, and useful input. The purpose of this study was to determine if the experience and gender of faculty members contribute to their ratings of students in a military medical field practicum. This information is important for fair ratings of students. Three research questions were addressed: Were there differences between new versus experienced faculty raters? Were there differences in assessments provided by female and male faculty members? Did gender of faculty raters impact ratings of female and male students?.

Materials and Methods

This study examined trained faculty evaluators’ ratings of three cohorts of medical students during 2015–2017 during a medical field practicum. Female (n = 80) and male (n = 161) faculty and female (n = 158) and male (n = 311) students were included. Within this dataset, there were 469 students and 241 faculty resulting in 5,599 ratings for each of six outcome variables that relate to overall leader performance, leader competence, and leader communication. Descriptive statistics were computed for all variables for the first four observations of each student. Descriptive analyses were performed for evaluator experience status and gender differences by each of the six variables. A multivariate analyses of variance was performed to examine whether there were differences between gender of faculty and gender of students.

Results

Descriptive analyses of the experience status of faculty revealed no significant differences between means on any of the rating elements. Descriptive analyses of faculty gender revealed no significant differences between female and male faculty ratings of the students. The overall MANOVA analyses found no statistically significant difference between female and male students on the combined dependent variables of leader performance for any of the four observations.

Conclusions

The study revealed that there were no differences in ratings of student leader performance based on faculty experience. In addition, there were no differences in ratings of student leader performance based on faculty gender.
Ethical Decision-Making at Intersections of Spirituality and Music Therapy in End-of-Life Care
Authors: Potvin Noah , Flynn Cathleen , Storm Jillian
Published: January 2020

Music therapists in end-of-life care settings are commonly requested by patients to self-disclose their spiritual beliefs and to participate in explicit spiritual practices or rituals. Four potential courses of action available to music therapists will be framed using an integrative ethical decision-making model in context of the American Music Therapy Association Code of Ethics. Stakeholdership, moderating obligations, and ethical values are concepts integral to this examination, providing music therapists dynamic constructs to continuously utilize when determining effective, culturally responsive ethical decisions. Specific ethical principles and codes are provided for additional points of reference, and recommendations are provided to guide future explorations into the ethical dimensions of music therapy and spirituality.
Identification of Meningioma Patients at High Risk of Tumor Recurrence Using MicroRNA Profiling
Authors: Slavik Hanus , Balik Vladimir , Vrbkova Jana , Rehulkova Alona , Vaverka Miroslav , Hrabalek Lumir , Ehrmann Jiri , Vidlarova Monika , Gurska Sona , Hajduch Marian , Srovnal Josef
Published: January 2020

BACKGROUND

Meningioma growth rates are highly variable, even within benign subgroups, with some remaining stable, whereas others grow rapidly.

OBJECTIVE

To identify molecular-genetic markers for more accurate prediction of meningioma recurrence and better-targeted therapy.

METHODS

Microarrays identified microRNA (miRNA) expression in primary and recurrent meningiomas of all World Health Organization (WHO) grades. Those found to be deregulated were further validated by quantitative real-time polymerase chain reaction in a cohort of 172 patients. Statistical analysis of the resulting dataset revealed predictors of meningioma recurrence.

RESULTS

Adjusted and nonadjusted models of time to relapse identified the most significant prognosticators to be miR-15a-5p, miR-146a-5p, and miR-331-3p. The final validation phase proved the crucial significance of miR-146a-5p and miR-331-3p, and clinical factors such as type of resection (total or partial) and WHO grade in some selected models. Following stepwise selection in a multivariate model on an expanded cohort, the most predictive model was identified to be that which included lower miR-331-3p expression (hazard ratio [HR] 1.44; P < .001) and partial tumor resection (HR 3.90; P < .001). Moreover, in the subgroup of total resections, both miRNAs remained prognosticators in univariate models adjusted to the clinical factors.

CONCLUSION

The proposed models might enable more accurate prediction of time to meningioma recurrence and thus determine optimal postoperative management. Moreover, combining this model with current knowledge of molecular processes underpinning recurrence could permit the identification of distinct meningioma subtypes and enable better-targeted therapies.
A Deeper Dive Into Antibiotic Stewardship Needs: A Multihospital Survey
Authors: Vaughn Valerie M , Petty Lindsay A , Flanders Scott A , Malani Anurag N , Patel Twisha , Bernstein Steven J , Hsaiky Lama M , Thyagarajan Rama , Osterholzer Danielle , McLaughlin Elizabeth , Horowitz Jennifer K , Gandhi Tejal N
Published: January 2020

In a 2016 survey of 46 Michigan hospitals, we identified four key needs for antibiotic stewardship: clinically-relevant antibiotic data, monitoring compliance, syndrome-specific interventions, and discharge stewardship. A stewardship initiative now addresses these needs within the Michigan Hospital Medicine Safety Consortium.
Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia
Authors: Gouel-Cheron Aurelie , Nason Martha , Rupert Adam , Sheikh Virginia , Robby Greg , Fahle Gary A , Sereti Irini
Published: January 2020

Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event.

ClinicalTrials.gov Identifier . NCT00286767.
Impact of Raltegravir or Efavirenz on Cell-Associated Human Immunodeficiency Virus-1 (HIV-1) Deoxyribonucleic Acid and Systemic Inflammation in HIV-1/Tuberculosis Coinfected Adults Initiating Antiretroviral Therapy
Authors: Delagreverie Héloïse M , Bauduin Claire , De Castro Nathalie , Grinsztejn Beatriz , Chevrier Marc , Jouenne Fanélie , Mourah Samia , Kalidi Issa , Pilotto Jose Henrique , Brites Carlos , Tregnago Barcellos Nemora , Amara Ali , Wittkop Linda , Molina Jean-Michel , Delaugerre Constance
Published: January 2020

Background

In view of the fast viremia decline obtained with integrase inhibitors, we studied the respective effects of initiating efavirenz (EFV) or raltegravir (RAL)-based antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV)-1 deoxyribonucleic acid (DNA) levels and inflammation biomarkers in the highly inflammatory setting of advanced HIV-1 disease with tuberculosis (TB) coinfection.

Methods

We followed cell-associated HIV-1 DNA, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), soluble CD14 and D-Dimer levels for 48 weeks after ART initiation in the participants to the ANRS12-180 REFLATE-TB study. This phase II open-label randomized study included ART-naive people with HIV and TB treated with rifampicin to receive RAL 400 mg twice daily (RAL400), RAL 800 mg twice daily (RAL800) or EFV 600 mg QD with tenofovir and lamivudine.

Results

In 146 participants, the median (interquartile range [IQR]) week (W)0 HIV-1 DNA level was 4.7 (IQR, 4.3–5.1) log10 copies/106 CD4+, and the reduction by W48 was −0.8 log10 copies/106 CD4+ on EFV, −0.9 on RAL400, and −1.0 on RAL800 (P = .74). Baseline median (IQR) hsCRP, IL-6, sCD14, and D-Dimer levels were 6.9 (IQR, 3.3–15.6) mg/L, 7.3 (IQR, 3.5–12.3) pg/mL, 3221 (IQR, 2383–4130) ng/mL, and 975 (IQR, 535–1970) ng/mL. All biomarker levels decreased over the study: the overall W0–W48 mean (95% confidence interval) fold-change on ART was 0.37 (IQR, 0.28–0.48) for hsCRP, 0.42 (IQR, 0.35–0.51) for IL-6, 0.51 (IQR, 0.47–0.56) for sCD14, and 0.39 (IQR, 0.32–0.47) for D-Dimers. There were no differences in biomarker reduction across treatment arms.

Conclusions

In participants with HIV and TB, EFV, RAL400, or RAL800 effectively and equally reduced inflammation and HIV-1 DNA levels.
Lymphedema Signs, Symptoms, and Diagnosis in Women Who Are in Minority and Low-Income Groups and Have Survived Breast Cancer
Authors: Flores Ann Marie , Nelson Jason , Sowles Lee , Stephenson Rebecca G , Robinson Kathryn , Cheville Andrea , Sander Antoinette P , Blot William J
Published: January 2020

Background

Breast cancer–related lymphedema (BCRL) is a well-known side effect of cancer and its treatment with wide-ranging prevalence estimates.

Objective

This study describes associations between breast cancer–related lymphedema (BCRL) signs, symptoms, and diagnosis for women who were African American, white, or had a low income and survived breast cancer.

Design

This is a cross-sectional, observational study that used a computer-assisted telephone interview.

Methods

Women who had survived breast cancer were queried on the presence of 5 lymphedema signs and symptoms (edema in the breast, axilla, arm, and/or hand; tissue fibrosis; pitting; hemosiderin staining; heaviness) and whether they had a diagnosis of BCRL. Relationships between signs/symptoms and diagnosis for each group were evaluated with kappa and chi-square statistics.

Results

The study sample included 528 women who had survived breast cancer (266 white and 262 African American), with 514 reporting complete data on household income; 45% of the latter reported an annual household income of ≤$20,000. Women who were African American or had a low income were nearly twice as likely as women who were white to have any of 8 signs/symptoms of BCRL. Regardless of race and income, >50% of women with all BCRL signs and symptoms reported that they were not diagnosed with BCRL.

Limitations

The main limitations of our study are the lack of medical chart data and longitudinal design.

Conclusions

Women who were African American or had a low income and had survived breast cancer had a greater burden of BCRL signs and symptoms than women who were white. The lack of a strong association between BCRL signs, symptoms, and diagnosis suggests that BCRL may be underdiagnosed. These findings suggest that more rigorous screening and detection of BCRL—especially for women who are African American or have a low income—may be warranted. Cancer rehabilitation programs may be able to fill this gap.
Agile predators: private equity and the spread of shareholder value strategies to US for-profit colleges
Authors: Eaton Charlie
Published: January 2020

I argue that growth in private equity and publicly traded ownership of US for-profit colleges has created new shareholder-value pressures for schools to maximize returns for investors. Privately held firms, which had long dominated the sector, were converted to private equity ownership through 88 buyouts since 1987. Private equity managers then used IPOs to establish 20 of 35 publicly traded firms that operated in the sector. I use longitudinal panel analyses of 14,212 federally qualified colleges to show that schools under these ownership forms featured unusually high debts and low graduation rates for students. The results (a) provide some of the most robust evidence to date that shareholder value strategies of cost-cutting and implicit contract violations can adversely affect non-labor stakeholders; and (b) help to theorize the growing but understudied role of private equity as a transitional ownership form that spreads shareholder value strategies to privately held firms.
Global assessment of genetic paradigms of Pvmdr1 mutations in chloroquine-resistant Plasmodium vivax isolates
Authors: Spotin Adel , Mahami-Oskouei Mahmoud , Ahmadpour Ehsan , Parsaei Mahdi , Rostami Ali , Emami Shima , Gholipour Saba , Farmani Mostafa
Published: January 2020

Background

Chloroquine (CQ) is generally prescribed as the front-line antimalarial drug of choice to treat Plasmodium vivax infections; however, some clinical CQ-resistant P. vivax isolates have been indigenously reported around the world during the last decade.

Methods

In this study, P. vivax isolates (n=52) were obtained from autochthonous samples in southeast Iran during 2015–2017. The genomic DNA of samples was extracted, amplified (nested PCR) and sequenced by targeting the multidrug-resistance 1 gene. To verify the global genetic diversity of CQ-resistant P. vivax strains, the sequences of Pvmdr1 originating from Asia and the Americas were retrieved.

Results

A total of 46 haplotypes were grouped into three distinct geographical haplogroups. The haplotype diversity and occurrence rates of Pvmdr1 976F/1076L mutations indicate that the efficacy of CQ is being compromised in Mexico, China, Nicaragua, Thailand, Brazil (2016), Ethiopia, Mauritania (2012) and southwest India in the near future. The cladistic phylogenetic tree showed that Pvmdr1 sequences isolated from the southeast Asian clade has a partial sister relationship with the American clade.

Conclusions

The current findings will serve as a basis to develop appropriate malaria control strategies and public health policies in symptomatic imported malaria cases or plausible CQ-resistant P. vivax strains.
The conformational distribution of a major facilitator superfamily peptide transporter is modulated by the membrane composition
Authors: Male Tanya Lasitza , Bartels Kim , Wiggers Felix , Rosenblum Gabriel , Jungwirth Jakub , Hofmann Hagen , Löw Christian
Published: January 2020

While structural biology aims at explaining the biological function of membrane proteins with their structure, it is unclear how these proteins are modulated by the complex lipid composition of membranes. Here, we address this question by mapping the conformational distribution of the bacterial oligopeptide transporter DtpA using single-molecule fluorescence spectroscopy. We show that DtpA populates ensembles of conformers that respond sensitively to the environment. Detergents trap the transporter in an inward-open ensemble in which the substrate binding site faces the cytosol. However, re-constitution in Saposin nanoparticles with different lipid compositions, reveal a plethora of alternative conformations, including a fully inward-open ensemble whose existence had not been anticipated before. The relative abundance of these ensembles depends on the lipid composition of the nanoparticles. Our results therefore demonstrate that membranes sensitively affect the structural distribution of DtpA and we expect this to be a general property of membrane proteins.
Decoding differential gene expression
Authors: Tasaki Shinya , Gaiteri Chris , Mostafavi Sara , Wang Yanling
Published: January 2020

Identifying the molecular mechanisms that control differential gene expression (DE) is a major goal of basic and disease biology. Combining the strengths of systems biology and deep learning in a model called DEcode, we are able to predict DE more accurately than traditional sequence-based methods, which do not utilize systems biology data. To determine the biological origins of this accuracy, we identify the most predictive regulators and types of regulatory interactions in DEcode, contrasting their roles across many human tissues. Diverse systems biology, ontological and disease-related assessments all point to the predominant influence of post-translational RNA-binding factors on DE. Through the combinatorial gene regulation that is captured in DEcode, it is even possible to predict relatively subtle person-to-person variation in gene expression. We demonstrate the broad applicability of these clinically-relevant predictions by predicting drivers of aging throughout the human lifespan, gene coexpression relationships on a genome-wide scale, and frequent DE in diverse conditions. Researchers can freely access DEcode to utilize genomic big data in identifying influential molecular mechanisms for any human expression data - www.differentialexpression.org.
Population Analysis of Extracellular Vesicles in Microvolumes of Biofluids
Authors: Maia Joana , Batista Silvia , Couto Nuno , Gregório Ana C. , Bodo Cristian , Elzanowska Julia , Moraes Maria Carolina Strano , Costa-Silva Bruno
Published: January 2020

Extracellular Vesicles (EVs), membrane vesicles released by all cells, are emerging mediators of cell-cell communication. By carrying biomolecules from tissues to biofluids, EVs have attracted attention as non-invasive sources of clinical biomarkers in liquid biopsies. Although frequently employed for content characterization of EVs, the study of bulk preparations lacks information on sub-populations and the intrinsic heterogeneity of vesicles. Importantly, these strategies also difficult the characterization of EVs from small quantities of samples. We here present a Flow Cytometry strategy that enables detailed population analysis of EVs, at the same time decreasing sample volume requirements and accelerating the overall processing time. We show its unique application for quality control of isolates of EVs by comparing the proportion of vesicular and non-vesicular particles in samples prepared by different protocols. In addition, we demonstrate its suitability for the study of populations of EVs from samples characterized by challenging small volumes. To illustrate that, we perform longitudinal non-lethal analysis of EVs in mouse plasma and in single-animal collections of murine vitreous humor. By allowing for the analysis of EVs from minimal amounts of sample, our Flow Cytometry strategy has an unexplored potential in the study of EVs in clinical samples with intrinsically limited volumes. When compared to conventional methods, it also multiplies by several times the number of different analytes that can be studied from a single collection of biofluid.
Dendritic integration in olfactory bulb granule cells: Thresholds for lateral inhibition and role of active conductances upon simultaneous activation
Authors: Müller Max , Egger Veronica
Published: January 2020

The inhibitory axonless olfactory bulb granule cells (GCs) form reciprocal dendrodendritic synapses with mitral and tufted cells via large spines, mediating recurrent and lateral inhibition. Rat GC dendrites are excitable by local Na+spine spikes and global Ca2+- and Na+-spikes. To investigate the transition from local to global signaling without Na+channel inactivation we performed simultaneous holographic two-photon uncaging in acute brain slices, along with whole-cell recording and dendritic Ca2+imaging. Less than 10 coactive reciprocal spines were sufficient to generate diverse regional and global signals that also included local dendritic Ca2+- and Na+-spikes (D-spikes). Individual spines could sense the respective signal transitions as increments in Ca2+entry. Dendritic integration was mostly linear until a few spines below global Na+-spike threshold, where often D-spikes set in. NMDARs strongly contributed to active integration, whereas morphological parameters barely mattered. In summary, thresholds for GC-mediated bulbar lateral inhibition are low.
Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cellsin vitro
Authors: Salcedo-Jiménez Ramés , Koenig Judith , Lee Olivia , Gibson Thomas W.G. , Madan Pavneesh , Koch Thomas G.
Published: January 2020

Extracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapiesin vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory propertiesin vitro.Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties.In vivostudies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.
Differential risk of incident cancer in patients with heart failure: A nationwide population-based cohort study
Authors: Kwak Soongu , Kwon Soonil , Lee Seo-Young , Yang Seokhun , Lee Hyun-Jung , Lee Heesun , Park Jun-Bean , Han Kyungdo , Kim Yong-Jin , Kim Hyung-Kwan
Published: January 2020

Background

Heart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database.

Methods and findings

This study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015. During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%,p<0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.61 - 1.68). The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05 - 1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF.

Conclusions

Cancer incidence is higher in patients with HF than in the general population. Active surveillance of coexisting malignancy needs to be considered in these patients.
Learning from invariants predicts upcoming behavioral choice from spiking activity in monkey V1
Authors: Koren Veronika , Andrei Ariana R. , Hu Ming , Dragoi Valentin , Obermayer Klaus
Published: January 2020

Animals frequently make decisions based on sensory cues. In such a setting, the overlap in the information on the stimulus and on the choice is crucial for the formation of informed behavioral decisions. Yet, how the information on the stimulus and on the choice interact in the brain is poorly understood. Here, we study the representation of a binary decision variable in the primary visual cortex (V1) while macaque monkeys perform delayed match-to-sample task on naturalistic visual stimuli close to psychophysical threshold. Using population vectors, we demonstrate the overlap in decoding spaces on binary stimulus classes “match/non-match” and binary choices “same /different” of the animal. Leveraging this overlap, we use learning from the invariant information across the two classification problems to predict the choice of the animal as a time-dependent population signal. We show the importance of the across-neuron organization and the temporal structure of spike trains for the decision signal and suggest how noise correlations between neurons with similar decoding selectivity are helpful for the accumulation of the decision signal. Finally, we show that decision signal is primarily carried by bursting neurons in the superficial layers of the cortex.

Author summary

V1 is necessary for normal visual processing and is known to process features of visual stimuli such as orientation, but whether V1 also encodes behavioral decisions is an unresolved issue, with conflicting evidence. Here, we demonstrate that V1 encodes a mixed variable that contains the information about the stimulus as well as about the choice. We learn the structure of population responses in trials pertaining to the variable “stimulus+choice”, and apply the resulting population vectors to trials that differ only about the choice of the animal, but not about the stimulus class. Moreover, we learn structure of population responses on time-averaged data and then apply it on time-dependent (spiking) data. During the late phase of the trial, this procedure allows to predict the upcoming choice of the animal with a time-dependent population signal. The spiking signal of small neural population is sparse, and we hypothesize that positive correlations between neurons in the same decoding pool help the transmission of the decision-related information downstream. We find that noise correlations in the same decoding pool are significantly stronger than across coding pools, which corroborates our hypothesis on the benefit of noise correlations for the read-out of a time-dependent population signal.
Ephrin-B2 Paces Neuronal Production in the Developing Neocortex
Authors: Kischel Anthony , Audouard Christophe , Fawal Mohamad-Ali , Davy Alice
Published: January 2020

Background

During mammalian cerebral cortex development, different types of projection neurons are produced in a precise temporal order and in stereotypical numbers. The mechanisms regulating timely generation of neocortex projection neurons and ensuring production in sufficient numbers of each neuronal identity is only partially understood.

Results

Here, we show that ephrin-B2, a member of the Eph:ephrin cell-to-cell communication pathway, sets the neurogenic tempo in the neocortex. Indeed, conditional mutant embryos for ephrin-B2 exhibit a transient delay in neurogenesis and acute stimulation of Eph signaling by in utero injection of synthetic ephrin-B2 led to a transient increase in neuronal production. Using genetic approaches we show that ephrin-B2 acts on neural progenitors to control their differentiation in a juxtacrine manner. Unexpectedly, we observed that perinatal neuron numbers recovered following both loss or gain of ephrin-B2, highlighting the ability of neural progenitors to adapt their behavior to the state of the system in order to produce stereotypical numbers of neurons.

Conclusions

Altogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasizes the plasticity of neuronal production in the neocortex.
Akt/Foxo pathway activation switches apoptosis to senescence in short telomere zebrafish
Authors: El-Maï Mounir , Marzullo Marta , de Castro Inês Pimenta , Ferreira Miguel Godinho
Published: January 2020

Progressive telomere shortening during lifespan is associated with increased genome instability, block to cell proliferation and aging. Apoptosis and senescence are the two main cellular outcomes upon irreversible cell damage. In this study, we show a transition between apoptosis to senescence in cells of two independent tissues in telomerase zebrafish mutants. In young mutants, proliferative tissues exhibit defects in cell proliferation and p53-dependent apoptosis, but no senescence. Progressively, these tissues display signs of tissue dysfunction, loss of cellularity and increased senescence. These alterations are accompanied by an activation of pro-proliferative stimulus mediated by AKT. Consequently, FoxO1 and FoxO4 transcriptional factors are inactivated, reducing SOD2 levels, causing an increase in ROS. These alterations elicit the activation of the zebrafish p16/15 and senescence. Thus, upon telomere shortening in aging, early apoptosis induces compensatory proliferation. However, progressive decline in cell proliferation results in tissue damage and proliferative signals, promoting a switch to senescence.
Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach
Authors: Sarkar Bishajit , Ullah Md. Asad
Published: January 2020

Herpes Simplex Virus (HSV) is an infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV viruses, HSV-1 and HSV-2, are the most dangerous HSV viruses. Every year, millions of people get infected with this menacing virus, however, no satisfactory treatment or vaccine has not yet been discovered to fight against HSV. Although there are some anti-viral therapies, however, studies have showed that such anti-viral therapies may also fail to provide good impact. In this study, a possible subunit vaccine against HSV-1, strain-17, was designed using the tools and reverse vaccinology and bioinformatics. Three potential antigenic envelope glycoproteins were selected from nine envelope glycoproteins, for possible vaccine construction. Potential epitopes capable of inducing high immunogenic response and at the same time have non-allergenicity and conservancy across other strains and species, were selected by some robust analysis, for vaccine construction. Finally, three possible vaccines were designed. Each of the vaccine construct differ from each other only in their adjuvant sequences and based on molecular docking analysis, one best vaccine construct was selected for molecular dynamics simulation study and in silico codon adaptation. The experiment showed that the selected best vaccine should be good candidate against HPV-1, strain-17. However, wet lab study should be conducted on the suggested vaccine(s) for confirming their potentiality, safety and efficacy.