bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune modulation attenuates infantile neuronal ceroid lipofuscinosis in mice before and after disease onset
Authors: Groh Janos , Berve Kristina , Martini Rudolf 
Published: March 2021

AbstractTargeting neuroinflammation in models for infantile and juvenile forms of neuronal ceroid lipofuscinosis (NCL, CLN disease) with the clinically established immunomodulators fingolimod and teriflunomide significantly attenuates the neurodegenerative phenotype when applied preventively, i.e. before the development of substantial neural damage and clinical symptoms. Here, we show that in a mouse model for the early onset and rapidly progressing CLN1 form, more complex clinical phenotypes like disturbed motor coordination and impaired visual acuity are also ameliorated by immunomodulation. Moreover, we show that the disease outcome can be attenuated even when fingolimod and teriflunomide treatment starts after disease onset, i.e. when neurodegeneration is ongoing and clinical symptoms are detectable. In detail, treatment with either drug led to a reduction in T-cell numbers and microgliosis in the CNS, although not to the same extent as upon preventive treatment. Pharmacological immunomodulation was accompanied by a reduction of axonal damage, neuron loss and astrogliosis in the retinotectal system and by reduced brain atrophy. Accordingly, the frequency of myoclonic jerks and disturbed motor coordination were attenuated. Overall, disease alleviation was remarkably substantial upon therapeutic treatment with both drugs, although less robust than upon preventive treatment. To test the relevance of putative immune-independent mechanisms of action in this model, we treated CLN1 mice lacking mature T- and B-lymphocytes. Immunodeficient CLN1 mice showed, as previously reported, an improved neurological phenotype in comparison with genuine CLN1 mice which could not be further alleviated by either of the drugs, reflecting a predominantly immune-related therapeutic mechanism of action. The present study supports and strengthens our previous view that repurposing clinically approved immunomodulators may alleviate the course of CLN1 disease in human patients, even though diagnosis usually occurs when symptoms have already emerged.
Beyond good intentions: questioning the ‘leaving no one behind’ agenda in global development, evidence from Pakistan
Authors: Farooq Laila S 
Published: March 2021

Abstract
This paper looks at how global development projects implemented through non-governmental organizations (NGOs) engage with the Sustainable Development Goals promise of ethnic inclusion. Using beneficiary representation as an indicator, we conducted Focus Group Discussions and interviews with non-profit sector practitioners in Pakistan. Responses show that NGOs often use practices that reinforce existing biases, including community outreach through public spaces, dominant languages and informal social circles. Such practices lead to ethnic minorities being underrepresented. Furthermore, international actors have encouraged the non-profit sector in Pakistan to be more competitive, pushing resources away from community mobilization and rewarding efficiency over commitment. This shift from normative ideas of inclusion leads to selection practices that are cost efficient but not inclusive. Several recommendations are made in this regard.
Decoding of Attentional State Using High-Frequency Local Field Potential Is As Accurate As Using Spikes
Authors: Prakash Surya S , Das Aritra , Kanth Sidrat Tasawoor , Mayo J Patrick , Ray Supratim 
Published: March 2021

Abstract
Local field potentials (LFPs) in visual cortex are reliably modulated when the subject’s focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spikes. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spikes was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found in rhesus monkeys that LFPs during neutral cueing were also intermediate between cued and uncued conditions. For a single electrode, attention was more discriminable using high frequency (&gt;30 Hz) LFP power than spikes, which is expected because LFP represents a population signal and therefore is expected to be less noisy than spikes. However, previous studies have shown that when multiple electrodes are used, spikes can outperform LFPs. Surprisingly, in our study, spikes did not outperform LFPs when discriminability was computed using multiple electrodes, even though the LFP activity was highly correlated across electrodes compared with spikes. These results constrain the spatial scale over which attention operates and highlight the usefulness of LFPs in studying attention.
Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial
Authors: Laurens Matthew B , Mungwira Randy G , Nampota Nginache , Nyirenda Osward M , Divala Titus H , Kanjala Maxwell , Mkandawire Felix A , Galileya Lufina Tsirizani , Nyangulu Wongani , Mwinjiwa Edson , Downs Matthew , Tillman Amy , Taylor Terrie E , Mallewa Jane , Plowe Christopher V , van Oosterhout Joep J , Laufer Miriam K 
Published: March 2021

AbstractBackgroundDaily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.MethodsWe conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of &gt;250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3–4 events, using Cox proportional hazards modeling, in an intention-to-treat population.Results1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: −14%–47%; P = .20) versus no prophylaxis and 25% (−10%–48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3–51%; P = .032) and 32% (4–51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P &lt; .001).ConclusionsMalawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3–4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2–4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa.Clinical Trials Registration. NCT01650558.
The Collision Avoidance and Situation-Aware Media Access Scheme Using the Registered-Backoff-Time Method for the IEEE 802.11ah-Based IoT Wireless Networks
Authors: Cheng Rung-Shiang , Li Yin-Ming , Huang Chung-Ming 
Published: March 2021

AbstractIEEE 802.11ah is a new protocol designed for Internet of Things (IoT). IEEE 802.11ah uses a hierarchical ID assignment schema and designs the corresponding channel access method such that stations can access channel alternatively through the four-level’s hierarchical channel access structure. Nevertheless, collisions still cannot be effectively avoided in a dense IOT networking environment using the legacy IEEE 802.11ah. The work proposed the registration-based situation-aware access extension (RSAE) control scheme to avoid collisions, decrease backoff’s waiting time and improve slot utilization through the following two ways: (i) in contrast to the traditional CSMA/CA protocol that generates the backoff time for the next channel access after the collision happened, registering the backoff time to AP for scheduling the next channel access before the collision happens; (ii) extending the channel accessing’s privilege of those stations that did not complete the data transmission/receiving in the current slot to the available time of the next slot. Comparing with the legacy IEEE 802.11ah, the performance evaluation of the proposed RSAE scheme shown that it still can have a better throughput and a lower collision rate when there is a bigger number of stations in a slot.
Piero Sraffa and Raffaello Piccoli: Two Italian Scholars in Cambridge 1929–1932
Authors: Morra Lucia 
Published: March 2021

Abstract
Sraffa’s diaries report that from June 1929 until late 1932 he often met with the literary scholar, poet and philosopher Raffaello Piccoli, Professor of Italian in the University of Cambridge. After a brief biographical sketch of Piccoli, the paper reconstructs the story of their friendship, thus contributing to the reconstruction of Sraffa’s biography in 1929–1932. It also considers their meetings with Carlo Rosselli in 1929–1931, together with their common friendship with Ludwig Wittgenstein.
Workers in the crowd: the labor market impact of the online platform economy
Authors: Cantarella Michele , Strozzi Chiara 
Published: March 2021

AbstractWe compare individuals engaged in online crowdwork against workers in traditional occupations from the United States and Europe, investigating the determinants of access into crowd employment and the nature of the deterioration of salary conditions and job quality characterizing these markets. We do so by matching responses from comparable working conditions surveys, and controlling for most individual and socio-economic characteristics affecting pay. We find that most differences in earnings are largely unexplained by the ability of individuals, and that labor in crowdwork is vastly under-utilized.
Ticagrelor Increases Platelet-Mediated Staphylococcus aureus Killing, Resulting in Clearance of Bacteremia
Authors: Ulloa Erlinda R , Uchiyama Satoshi , Gillespie Robert , Nizet Victor , Sakoulas George 
Published: March 2021

Abstract
Platelets are a critical immune defense against Staphylococcus aureus bloodstream infections. Staphylococcus aureus α-toxin is a virulence factor that decreases platelet viability and accelerates platelet clearance. It has been shown that ticagrelor blocks α-toxin–mediated platelet injury and resulting thrombocytopenia, protecting mice in a lethal S. aureus sepsis model. We now present the use of ticagrelor as adjunctive therapy in a patient with a S. aureus endovascular infection and thrombocytopenia, associated with restoration of platelet count and bacteremia clearance. Ticagrelor enhanced platelet killing of the S. aureus bloodstream isolate from the treated patient in vitro.
VraCP regulates cell wall metabolism and antibiotic resistance in vancomycin-intermediateStaphylococcus aureusstrain Mu50
Authors: Wang Wanying , Sun Baolin 
Published: March 2021

AbstractObjectivesVancomycin-intermediate Staphylococcus aureus (VISA) is increasingly being reported. Previous studies have shown that vraC and vraP may be involved in vancomycin resistance, although the molecular mechanism remains elusive.MethodsThe vraC (SAV0577), vraP (SAV0578) and vraCP mutants were constructed in Mu50 by allelic replacement. Some common VISA phenotypes were assessed in mutants, such as, susceptibility to the cell wall-associated antibiotics, cell wall thickness, autolysis activity and growth rate. RT-qPCR was performed to reveal the differential genes associated with these phenotypes. The binding abilities of VraC and VraCP to the promoters of target genes were determined by electrophoretic mobility shift assay (EMSA).ResultsVraP forms a stable complex with VraC to preserve their own stability. The vraC, vraP and vraCP mutants exhibited increased susceptibility to the cell wall-associated antibiotics and thinner cell walls compared with the WT strain. Consistent with these phenotypes, RT-qPCR revealed downregulated transcription of glyS, sgtB, ddl and alr2, which are involved in cell wall biosynthesis. Moreover, the transcription of cell wall hydrolysis genes, including sceD, lytM and isaA, was significantly downregulated, supporting the finding that mutants exhibited reduced autolysis rates. EMSA confirmed that both VraC and VraCP can directly bind to the sceD, lytM and isaA promoter regions containing the consensus sequence (5′-TTGTAAN2AN3TGTAA-3′), which is crucial for the binding of VraCP with target genes. GFP-reporter assays further revealed VraC and VraCP can enhance promoter activity of sceD to positively regulate its expression.ConclusionsvraCP plays a significant role in cell wall metabolism and antibiotic resistance in Mu50.
β-Amyloid in Cerebrospinal Fluid: How to Keep It Floating (Not Sticking) by Standardization of Preanalytic Processes and Collection Tubes
Authors: Strand Heidi , Garabet Lamya , Bjelke Börje , Sithiravel Cindhya , Hardang Ingrid Marie , Moe Morten K 
Published: March 2021

Abstract

Background
Phosphorylated tau (pTau), total tau (tTau), and β-amyloid (Aβ) are established cerebrospinal fluid (CSF) biomarkers used to help diagnose Alzheimer disease. Preanalytic workups of CSF samples lack harmonization, making interlaboratory comparison of these biomarkers challenging. The Aβ adsorbs to sample tubes, yielding underestimated concentrations, and may result in false Alzheimer disease diagnosis. Our primary aim was to compare Aβ recovery across multiple polypropylene tubes and to test the stability of tTau, pTau, and Aβ in the best performing tube.

Methods
Eight polypropylene tubes were tested using 3 CSF pools with Aβ concentrations &lt;500, 500–1000, and &gt;1000 ng/L. All samples were analyzed in duplicate. Tubes were cut open to assess their different infrared adsorption spectra. Freshly drawn CSF from 14 patients was distributed into 4 Sarstedt 5-mL (no. 63.504.027; Sar5CSF) tubes, left at room temperature for up to 7 days, and analyzed for pTau, tTau, and Aβ by ELISA.

Results
Two Sarstedt 5-mL tubes and a Sarstedt 10-mL (Sar10CSF) tube showed significantly higher Aβ recovery at all 3 concentrations compared with the 5 other tubes. The infrared adsorption spectra of Sar10CSF and Sar5CSF tubes were practically identical, unlike the other tubes. No significant loss of pTau, tTau, and Aβ was observed in CSF left at room temperature for up to 7 days (P &gt; 0.05).

Conclusions
Recovery of Aβ from Sar5CSF tubes is equivalent to Aβ recovery from Sar10CSF tubes. Levels of pTau, tTau, and Aβ were stable for at least 7 days at room temperature but not at 37 °C.
CancelRx: a health IT tool to reduce medication discrepancies in the outpatient setting
Authors: Watterson Taylor L , Stone Jamie A , Brown Roger , Xiong Ka Z , Schiefelbein Anthony , Ramly Edmond , Kleinschmidt Peter , Semanik Michael , Craddock Lauren , Pitts Samantha , Woodroof Taylor , Chui Michelle A 
Published: March 2021

Abstract

Objective
Medication list discrepancies between outpatient clinics and pharmacies can lead to medication errors. Within the last decade, a new health information technology (IT), CancelRx, emerged to send a medication cancellation message from the clinic’s electronic health record (EHR) to the outpatient pharmacy’s software. The objective of this study was to measure the impact of CancelRx on reducing medication discrepancies between the EHR and pharmacy dispensing software.

Materials and Methods
CancelRx was implemented in October 2017 at an academic health system. For 12 months prior, and 12 months after CancelRx implementation, data were collected on discontinued medications in the health system’s EHR and whether those prescriptions were successfully discontinued in the pharmacy’s dispensing software. An interrupted time series analysis was conducted to model the occurrence of prescriptions successfully discontinued over time.

Results
There was an immediate (lag = 0), significant (P &lt; 0.001), and sustained (post-implementation slope 0.02) increase in the proportion of successful medication discontinuations after CancelRx implementation (from 34% to 93%). CancelRx had variable impact based on whether the clinic was primary care (71.4% change prepost) or specialty care (53.9% change prepost). CancelRx reduced the time between when a medication was discontinued in the clinic EHR and pharmacy dispensing software.

Conclusion
CancelRx automated a manual process and illustrated the role for health IT in communicating medication discontinuations between clinics and pharmacies. Overall, CancelRx had a marked benefit on medication list discrepancies and illustrated how health IT can be used across different settings to improve patient care.
Changes in Mammography Use by Women’s Characteristics During the First 5 Months of the COVID-19 Pandemic
Authors: Sprague Brian L , Lowry Kathryn P , Miglioretti Diana L , Alsheik Nila , Bowles Erin J A , Tosteson Anna N A , Rauscher Garth , Herschorn Sally D , Lee Janie M , Trentham-Dietz Amy , Weaver Donald L , Stout Natasha K , Kerlikowske Karla 
Published: March 2021

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) pandemic led to a near-total cessation of mammography services in the United States in mid-March 2020. It is unclear if screening and diagnostic mammography volumes have recovered to prepandemic levels and whether use has varied by women’s characteristics.MethodsWe collected data on 461 083 screening mammograms and 112 207 diagnostic mammograms conducted during January 2019 through July 2020 at 62 radiology facilities in the Breast Cancer Surveillance Consortium. We compared monthly screening and diagnostic mammography volumes before and during the pandemic stratified by age, race and ethnicity, breast density, and family history of breast cancer.ResultsScreening and diagnostic mammography volumes in April 2020 were 1.1% (95% confidence interval [CI] = 0.5% to 2.4%) and 21.4% (95% CI = 18.7% to 24.4%) of the April 2019 prepandemic volumes, respectively, but by July 2020 had rebounded to 89.7% (95% CI = 79.6% to 101.1%) and 101.6% (95% CI = 93.8% to 110.1%) of the July 2019 prepandemic volumes, respectively. The year-to-date cumulative volume of screening and diagnostic mammograms performed through July 2020 was 66.2% (95% CI = 60.3% to 72.6%) and 79.9% (95% CI = 75.4% to 84.6%), respectively, of year-to-date volume through July 2019. Screening mammography rebound was similar across age groups and by family history of breast cancer. Monthly screening mammography volume in July 2020 for Black, White, Hispanic, and Asian women reached 96.7% (95% CI = 88.1% to 106.1%), 92.9% (95% CI = 82.9% to 104.0%), 72.7% (95% CI = 56.5% to 93.6%), and 51.3% (95% CI = 39.7% to 66.2%) of the July 2019 prepandemic volume, respectively.ConclusionsDespite a strong overall rebound in mammography volume by July 2020, the rebound lagged among Asian and Hispanic women, and a substantial cumulative deficit in missed mammograms accumulated, which may have important health consequences.
Including beyond-linear halo bias in halo models
Authors: Mead A J , Verde L 
Published: March 2021

ABSTRACT
We derive a simple prescription for including beyond-linear halo bias within the standard, analytical halo-model power spectrum calculation. This results in a corrective term that is added to the usual two-halo term. We measure this correction using data from N-body simulations and demonstrate that it can boost power in the two-halo term by a factor of ∼2 at scales $k\sim 0.7\, h\mathrm{Mpc}^{-1}$, with the exact magnitude of the boost determined by the specific pair of fields in the two-point function. How this translates to the full power spectrum depends on the relative strength of the one-halo term, which can mask the importance of this correction to a greater or lesser degree, again depending on the fields. Generally, we find that our correction is more important for signals that arise from lower mass haloes. When comparing our calculation to simulated data, we find that the underprediction of power in the transition region between the two- and one-halo terms, which typically plagues halo-model calculations, is almost completely eliminated when including the full non-linear halo bias. We show improved results for the autospectra and cross-spectra of galaxies, haloes, and matter. In the specific case of matter–matter or matter–halo power, we note that a large fraction of the improvement comes from the non-linear biasing between low- and high-mass haloes. We envisage our model being useful in the analytical modelling of cross-correlation signals. Our non-linear bias halo-model code is available at https://github.com/alexander-mead/BNL.
Non-Keplerian spirals, a gas-pressure dust trap, and an eccentric gas cavity in the circumbinary disc around HD 142527
Authors: Garg H , Pinte C , Christiaens V , Price D J , Lazendic J S , Boehler Y , Casassus S , Marino S , Perez S , Zuleta A 
Published: March 2021

ABSTRACTWe present ALMA observations of the 12CO, 13CO, C18O J = 2-1 transitions and the 1.3 mm continuum emission for the circumbinary disc around HD 142527, at an angular resolution of ≈ 0${_{.}^{\prime\prime}}$3. We observe multiple spiral structures in intensity, velocity, and velocity dispersion for the 12CO and 13CO gas tracers. A newly detected 12CO spiral originates from the dust horseshoe, and is rotating at super-Keplerian velocity or vertically ascending, whilst the interspiral gas is rotating at sub-Keplerian velocities. This new spiral possibly connects to a previously identified spiral, thus spanning &gt;360°. A spatial offset of 30 au is observed between the 12CO and 13CO spirals, to which we hypothesize that the gas layers are propagating at different speeds (surfing) due to a non-zero vertical temperature gradient. Leveraging the varying optical depths between the CO isotopologues, we reconstruct temperature and column density maps of the outer disc. Gas surface density peaks at r ≈ 180 au, coincident with the peak of continuum emission. Here, the dust grains have a Stokes number of ≈ 1, confirming radial and azimuthal trapping in the horseshoe. We measure a cavity radius at half-maximum surface density of ≈ 100 au, and a cavity eccentricity between 0.3 and 0.45.
microRNA-mediated translation repression through GYF-1 and IFE-4 in C. elegans development
Authors: Mayya Vinay K , Flamand Mathieu N , Lambert Alice M , Jafarnejad Seyed Mehdi , Wohlschlegel James A , Sonenberg Nahum , Duchaine Thomas F 
Published: March 2021

Abstract
microRNA (miRNA)-mediated gene silencing is enacted through the recruitment of effector proteins that direct translational repression or degradation of mRNA targets, but the relative importance of their activities for animal development remains unknown. Our concerted proteomic surveys identified the uncharacterized GYF-domain encoding protein GYF-1 and its direct interaction with IFE-4, the ortholog of the mammalian translation repressor 4EHP, as key miRNA effector proteins in Caenorhabditis elegans. Recruitment of GYF-1 protein to mRNA reporters in vitro or in vivo leads to potent translation repression without affecting the poly(A) tail or impinging on mRNA stability. Loss of gyf-1 is synthetic lethal with hypomorphic alleles of embryonic miR-35–42 and larval (L4) let-7 miRNAs, which is phenocopied through engineered mutations in gyf-1 that abolish interaction with IFE-4. GYF-1/4EHP function is cascade-specific, as loss of gyf-1 had no noticeable impact on the functions of other miRNAs, including lin-4 and lsy-6. Overall, our findings reveal the first direct effector of miRNA-mediated translational repression in C. elegans and its physiological importance for the function of several, but likely not all miRNAs.