bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundIn 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.MethodsWe 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.ResultsIn 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.ConclusionsIn 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

Abstract

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, &gt;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

AbstractI 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

Abstract

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

AbstractWhile 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.
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

AbstractExtracellular 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

AbstractThe 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

AbstractExtracorporeal 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

ABSTRACTBackgroundHeart 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 findingsThis 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.ConclusionsCancer 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

AbstractAnimals 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 summaryV1 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

ABSTRACTBackgroundDuring 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.ResultsHere, 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.ConclusionsAltogether, 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

ABSTRACTProgressive 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.