bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study
Authors: Namale Gertrude , Kamacooko Onesmus , Bagiire Daniel , Mayanja Yunia , Abaasa Andrew , Kilembe William , Price Matt , Ssemwanga Deogratius , Lunkuse Sandra , Nanyonjo Maria , Ssenyonga William , Mayaud Philippe , Newton Rob , Kaleebu Pontiano , Seeley Janet 
Published: July 2019

ObjectivesWe assessed the prevalence and risk factors associated with virological failure among female sex workers living with HIV on antiretroviral therapy (ART) in Kampala, Uganda.MethodsWe conducted a cross-sectional study between January 2015 and December 2016 using routinely collected data at a research clinic providing services to women at high risk of STIs including HIV. Plasma samples were tested for viral load from HIV-seropositive women aged ≥18 years who had been on ART for at least 6 months and had received adherence counselling. Samples from women with virological failure (≥1000 copies/mL) were tested for HIV drug resistance by population-based sequencing. We used logistic regression to identify factors associated with virological failure.ResultsOf 584 women, 432 (74%) with a mean age of 32 (SD 6.5) were assessed, and 38 (9%) were found to have virological failure. HIV resistance testing was available for 78% (28/38), of whom 82.1% (23/28) had at least one major drug resistance mutation (DRM), most frequently M184V (70%, 16/23) and K103N (65%, 15/23). In multivariable analysis, virological failure was associated with participant age 18–24 (adjusted OR (aOR)=5.3, 95% CI 1.6 to 17.9), self-reported ART non-adherence (aOR=2.6, 95% CI 1.2 to 5.8) and baseline CD4+ T-cell count ≤350 cells/mm3(aOR=3.1, 95% CI 1.4 to 7.0).ConclusionsA relatively low prevalence of virological failure but high rate of DRM was found in this population at high risk of transmission. Younger age, self-reported ART non-adherence and low CD4+ T-cell count on ART initiation were associated with increased risk of virological failure.
Immobilizing A Moving Target: CAR T Cells Hit CD22
Authors: Guedan Sonia , Delgado Julio 
Published: July 2019

Abstract
A key mechanism of resistance to chimeric antigen receptor–modified T cells (CAR-T) is loss or downregulation of target antigens. Low antigen expression on cancer cells prevents full CAR-T-cell activation and persistence. Pharmacologic modulation of target antigen expression offers a novel therapeutic strategy to drive more potent and durable responses.
See related article by Ramakrishna et al., p. 5329
Immune Checkpoint Blockade Enhances Shared Neoantigen-Induced T-cell Immunity Directed against Mutated Calreticulin in Myeloproliferative Neoplasms
Authors: Cimen Bozkus Cansu , Roudko Vladimir , Finnigan John P. , Mascarenhas John , Hoffman Ronald , Iancu-Rubin Camelia , Bhardwaj Nina 
Published: July 2019

Abstract

Somatic frameshift mutations in the calreticulin (CALR) gene are key drivers of cellular transformation in myeloproliferative neoplasms (MPN). All patients carrying these mutations (CALR+ MPN) share an identical sequence in the C-terminus of the mutated CALR protein (mut-CALR), with the potential for utility as a shared neoantigen. Here, we demonstrate that although a subset of patients with CALR+ MPN develop specific T-cell responses against the mut-CALR C-terminus, PD-1 or CTLA4 expression abrogates the full complement of responses. Significantly, blockade of PD-1 and CLTA4 ex vivo by mAbs and of PD-1 in vivo by pembrolizumab administration restores mut-CALR–specific T-cell immunity in some patients with CALR+ MPN. Moreover, mut-CALR elicits antigen-specific responses from both CD4+ and CD8+ T cells, confirming its broad applicability as an immunogen. Collectively, these results establish mut-CALR as a shared, MPN-specific neoantigen and inform the design of novel immunotherapies targeting mut-CALR.

Significance:
Current treatment modalities for MPN are not effective in eliminating malignant cells. Here, we show that mutations in the CALR gene, which drive transformation in MPN, elicit T-cell responses that can be further enhanced by checkpoint blockade, suggesting immunotherapies could be employed to eliminate CALR+ malignant cells in MPN.
This article is highlighted in the In This Issue feature, p. 1143
Delayed Cord Clamping versus Early Cord Clamping in Elective Cesarean Section: A Randomized Controlled Trial
Authors: Cavallin Francesco , Galeazzo Beatrice , Loretelli Vittoria , Madella Stefania , Pizzolato Martina , Visentin Silvia , Trevisanuto Daniele 
Published: July 2019

<b><i>Background:</i></b> Delaying cord clamping is recommended in order to assure placental transfusion. However, the evidence on cord management in elective cesarean section (CS) is limited. <b><i>Objective:</i></b> To compare delayed cord clamping (DCC) with early cord clamping (ECC) with regard to postnatal adaptation in neonates born through elective CS. <b><i>Methods:</i></b> All neonates born ≥39 weeks’ gestation born through elective CS were assigned to either the DCC or the ECC arm at a 1:1 ratio according to a computer-generated, randomized sequence. The primary outcome was the hematocrit at day 2 of life. Secondary outcomes included: preductal oxygen saturation and heart rate during the first 10 min of life; transcutaneous bilirubin at day 3; and neonatal blood pressures in the first 3 days of life. Additional outcomes included: time to first spontaneous breath; temperature at admission to normal nursery; weight at discharge; and maternal blood losses. <b><i>Results:</i></b> Eighty neonates were randomized to the DCC (<i>n</i> = 40) or the ECC (<i>n</i> = 40) arm. The hematocrit at day 2 was significantly higher in the DCC arm than in the ECC arm (mean difference: 6%; 95% CI 3–8; <i>p</i> &#x3c; 0.0001). The secondary outcome measures were not statistically different between the two arms. No infants needed phototherapy for hyperbilirubinemia during their hospital stay. <b><i>Conclusions:</i></b> Delaying cord clamping beyond 60 s increases the hematocrit at day 2 in neonates born through elective CS, without affecting maternal blood losses. Our findings suggest that DCC should be recommended in elective CS, but further studies are warranted to assess long-term outcomes.
Overview of the Antarctic Circumnavigation Expedition: Study of Preindustrial-like Aerosols and Their Climate Effects (ACE-SPACE)
Authors: Schmale Julia , Baccarini Andrea , Thurnherr Iris , Henning Silvia , Efraim Avichay , Regayre Leighton , Bolas Conor , Hartmann Markus , Welti André , Lehtipalo Katrianne , Aemisegger Franziska , Tatzelt Christian , Landwehr Sebastian , Modini Robin L. , Tummon Fiona , Johnson Jill S. , Harris Neil , Schnaiter Martin , Toffoli Alessandro , Derkani Marzieh , Bukowiecki Nicolas , Stratmann Frank , Dommen Josef , Baltensperger Urs , Wernli Heini , Rosenfeld Daniel , Gysel-Beer Martin , Carslaw Ken S. 
Published: July 2019

AbstractUncertainty in radiative forcing caused by aerosol–cloud interactions is about twice as large as for CO2 and remains the least well understood anthropogenic contribution to climate change. A major cause of uncertainty is the poorly quantified state of aerosols in the pristine preindustrial atmosphere, which defines the baseline against which anthropogenic effects are calculated. The Southern Ocean is one of the few remaining near-pristine aerosol environments on Earth, but there are very few measurements to help evaluate models. The Antarctic Circumnavigation Expedition: Study of Preindustrial-like Aerosols and their Climate Effects (ACE-SPACE) took place between December 2016 and March 2017 and covered the entire Southern Ocean region (Indian, Pacific, and Atlantic Oceans; length of ship track >33,000 km) including previously unexplored areas. In situ measurements covered aerosol characteristics [e.g., chemical composition, size distributions, and cloud condensation nuclei (CCN) number concentrations], trace gases, and meteorological variables. Remote sensing observations of cloud properties, the physical and microbial ocean state, and back trajectory analyses are used to interpret the in situ data. The contribution of sea spray to CCN in the westerly wind belt can be larger than 50%. The abundance of methanesulfonic acid indicates local and regional microbial influence on CCN abundance in Antarctic coastal waters and in the open ocean. We use the in situ data to evaluate simulated CCN concentrations from a global aerosol model. The extensive, available ACE-SPACE dataset (https://zenodo.org/communities/spi-ace?page=1&size=20) provides an unprecedented opportunity to evaluate models and to reduce the uncertainty in radiative forcing associated with the natural processes of aerosol emission, formation, transport, and processing occurring over the pristine Southern Ocean.
On the Linearity of the Stratospheric and Euro-Atlantic Sector Response to ENSO
Authors: Trascasa-Castro Paloma , Maycock Amanda C. , Scott Yiu Yu Yeung , Fletcher Jennifer K. 
Published: July 2019

Abstract
The dependence of the winter stratospheric and Euro-Atlantic climate response on ENSO amplitude is investigated using the HadGEM3 model. Experiments are performed with imposed east Pacific sea surface temperature perturbations corresponding to Niño-3.4 anomalies of ±0.75, 1.5, 2.25, and 3.0 K. In the North Pacific, El Niño (EN) deepens and shifts the Aleutian low eastward, while the equivalent magnitude La Niña (LN) perturbations drive anomalies of opposite sign that are around 4 times weaker. The muted North Pacific response to LN can be traced back to the weaker response of tropical convection and the associated anomalous Rossby wave source. The EN perturbations weaken the Arctic polar vortex, with the winter mean zonal mean zonal wind at 60°N and 10 hPa decreasing approximately linearly with Niño-3.4 anomaly by around −3.6 m s−1 K−1. For the strongest EN case (+3 K), the frequency of sudden stratospheric warmings (SSWs) increases by ~60% compared to the control experiment. Hence the results do not support a saturation of the stratospheric pathway for strong EN as suggested in previous literature. The equivalent amplitude LN perturbations cause a weak strengthening of the polar vortex and no substantial change in SSW frequency, in contrast to some reanalysis-based studies. EN induces a negative North Atlantic Oscillation (NAO) index throughout boreal winter, which increases approximately linearly with the Niño-3.4 anomaly by around −0.6 standard deviations K−1. Only the response to the strongest LN perturbations projects onto a weak positive NAO in November, suggesting that the mechanism for the Euro-Atlantic response to LN may be distinct from EN.
The Australian Northwest Cloudband: Climatology, Mechanisms, and Association with Precipitation
Authors: Reid Kimberley J. , Simmonds Ian , Vincent Claire L. , King Andrew D. 
Published: July 2019

Abstract
Australian northwest cloudbands (NWCBs) are continental-scale bands of continuous cloud that stretch from northwest to southeast Australia. In earlier studies, where the characteristics of NWCBs and their relationship with precipitation were identified from satellite imagery, there was considerable uncertainty in the results due to limited quality and availability of data. The present study identifies NWCBs from 31 years of satellite data using a pattern-matching algorithm. This new climatology is the longest record based entirely on observations. Our findings include a strong annual cycle in NWCB frequency, with a summer maximum and winter minimum, and a statistically significant increase in annual NWCB days over the period 1984–2014. Physical mechanisms responsible for NWCB occurrences are explored to determine whether there is a fundamental difference between summer and winter NWCBs as hypothesized in earlier studies. Composite analyses are used to reveal that a key difference between these is their genesis mechanisms. Whereas summer NWCBs are triggered by cyclonic disturbances, winter NWCBs tend to form when meridional sea surface temperature gradients trigger baroclinic instability. It was also found that while precipitation is enhanced over parts of Australia during a cloudband day, it is reduced in other regions. During a cloudband day, precipitation extremes are more likely over northwest, central, and southeast Australia, while the probability of extreme precipitation decreases in northeast and southwest Australia. Additionally, cold fronts and NWCBs can interact, leading to enhanced rainfall over Australia.
Practical Uncertainties in the Limited Predictability of the Record-Breaking Intensification of Hurricane Patricia (2015)
Authors: Nystrom Robert G. , Zhang Fuqing 
Published: July 2019

AbstractHurricane Patricia (2015) was a record-breaking tropical cyclone that was difficult to forecast in real time by both operational numerical weather prediction models and operational forecasters. The current study examines the potential for improving intensity prediction for extreme cases like Hurricane Patricia. We find that Patricia’s intensity predictability is potentially limited by both initial conditions, related to the data assimilation, and model errors. First, convection-permitting assimilation of airborne Doppler radar radial velocity observations with an ensemble Kalman filter (EnKF) demonstrates notable intensity forecast improvements over assimilation of conventional observations alone. Second, decreasing the model horizontal grid spacing to 1 km and reducing the surface drag coefficient at high wind speed in the parameterization of the sea surface–atmosphere exchanges is also shown to notably improve intensity forecasts. The practical predictability of Patricia, its peak intensity, rapid intensification, and the underlying dynamics are further investigated through a high-resolution 60-member ensemble initialized with realistic initial condition uncertainties represented by the EnKF posterior analysis perturbations. Most of the ensemble members are able to predict the peak intensity of Patricia, but with greater uncertainty in the timing and rate of intensification; some members fail to reach the ultimate peak intensity before making landfall. Ensemble sensitivity analysis shows that initial differences in the region beyond the radius of maximum wind contributes the most to the differences between ensemble members in Patricia’s intensification. Ensemble members with stronger initial primary and secondary circulations beyond the radius of maximum wind intensify earlier, are able to maintain the intensification process for longer, and thus reach a greater and earlier peak intensity.
Linkages between Extreme Precipitation Events in the Central and Eastern United States and Rossby Wave Breaking
Authors: Moore Benjamin J. , Keyser Daniel , Bosart Lance F. 
Published: July 2019

AbstractLinkages between extreme precipitation events (EPEs) in the central and eastern United States and synoptic-scale Rossby wave breaking are investigated using 1979–2015 climatologies of EPEs and upper-level potential vorticity (PV) streamers. The investigation focuses on two domains over the central and eastern United States, respectively, and emphasizes widespread EPEs, events exhibiting exceptionally large precipitation volumes. The relative frequency of PV streamers is found to be significantly enhanced relative to climatology immediately upstream of each domain during widespread EPEs. Majorities of the widespread EPEs in the central (~79%) and eastern (~56%) U.S. domains co-occur with a PV streamer positioned immediately upstream. Odds ratios of EPEs for days when a PV streamer occurs upstream of each domain indicate a strong, statistically significant association between EPEs and Rossby wave breaking. The strength of the EPE–Rossby wave breaking linkage, as measured by co-occurrence fractions and odds ratios, tends to increase with increasing EPE precipitation volume, such that the strongest linkage exists for widespread EPEs. Composite analyses reveal that Rossby wave breaking can result in widespread EPEs by establishing a persistent high-amplitude synoptic-scale wave pattern, within which strong poleward water vapor transport and ascent are forced over the EPE region immediately downstream of an elongated upper-level trough. Additional analyses demonstrate that, compared to corresponding null cases, Rossby wave breaking cases resulting in widespread EPEs exhibit a significantly higher-amplitude wave pattern that favors greater poleward transport of moist, conditionally unstable air and stronger ascent over the EPE region.
Detection of lesions depends on the DARTEL template used in group comparisons with voxel-based morphometry
Authors: Goto Masami , Kamatgata Koji , Saito Asami , Abe Osamu , Motoi Yumiko , Miyajima Masakazu , Nakajima Madoka 
Published: July 2019

Background In many brain volumetry reports, data from both controls and patients have been used to create the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) templates for spatial normalization, whereas some studies used data from only the control group. Purpose To investigate the association between lesion detection and the processes used in creating DARTEL template in group comparisons with voxel-based morphometry. Material and Methods Three-dimensional T1-weighted MRI data of 31 healthy controls, 31 patients with Alzheimer’s disease, and 31 patients with idiopathic normal pressure hydrocephalus were obtained using a 3-T magnetic resonance scanner. Segmented gray matter images were then deformed into three types of DARTEL templates using the Statistical Parametric Mapping 12 software. Results Processes 1 (DARTEL template with all individuals) and 2 (DARTEL template with healthy controls) showed significant lesions, as observed in previous reports, whereas process 3 (DARTEL template with individuals divided into two groups) showed significantly larger lesions than those noted with processes 1 and 2. Conclusion The present study demonstrated that lesion detection depends on the processes used in the creation of the DARTEL template.
Comparison of treatment outcomes in lumbar disc herniation patients treated with epidural steroid injections: interlaminar versus transforaminal approach
Authors: Bensler Susanne , Walde Melissa , Fischer Michael A , Pfirrmann Christian WA , Peterson Cynthia K , Sutter Reto 
Published: July 2019

BackgroundThe study describes the difference of pain reduction in interlaminar and transforaminal injections.PurposeTo compare treatment outcomes after interlaminar versus transforaminal epidural steroid injections in patients with disc herniations at the level L3/4–L5/S1 and analyze associated magnetic resonance imaging (MRI) findings.Material and MethodsThis retrospective comparative effectiveness outcome study included 198 patients with computed tomography (CT)-guided interlaminar (n = 99) or transforaminal (n = 99) epidural injections with particulate steroids. Pain levels at baseline and one day, one week, and one month after injection were assessed using the 11-point Numerical Rating Scale for Pain. Overall improvement was assessed after one day, one week, and one month using the Patients Global Impression of Change. MRI analysis was performed by two radiologists. Student’s t-test, Chi-square test, and Fisher’s exact test were calculated.ResultsBaseline pain scores were equal for interlaminar and transforaminal injections (6.23, SD = 2.10 vs. 5.84, SD = 2.02; P = 0.18). There were no significant differences in improvement between the interlaminar and transforaminal approach of epidural steroid injections after one day (30.5% vs. 21.2%, P = 0.432), one week (41.7% vs. 40.8%, P = 1.000), and one month (53.3% vs. 43.9%, P = 0.322), but there was a trend towards better effect of interlaminar injections at one day and one month. The change in Numerical Rating Scale for Pain scores showed no significant differences between the two cohorts after one day, one week, and one month ( P ≥ 0.115). None of the MR findings predicted a better or worse outcome ( P ≥ 0.171).ConclusionInterlaminar and transforaminal injections with particulate corticosteroids were equally effective, with a non-significant advantage of interlaminar injections at one day and one month. None of the MR findings were associated with treatment outcomes.
Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions
Authors: Bianchi Vanessa J. , Lee Adrienne , Anderson Jesse , Parreno Justin , Theodoropoulos John , Backstein David , Kandel Rita 
Published: July 2019

Background: Autologous chondrocyte implantation, which uses passaged chondrocytes, commonly leads to the formation of fibrocartilage. When chondrocytes are passaged to increase cell numbers, they lose their phenotype and ability to form hyaline cartilage. The use of transforming growth factor β (TGFβ) to redifferentiate passaged chondrocytes has been validated in vitro; however, it is unknown if redifferentiated chondrocytes will enhance defect repair when implanted in vivo. Furthermore, fibrin gel is used in orthopaedic surgery as a fixative and scaffold and could be an appropriate carrier to enhance retention of cells in the repair site. Purpose: To investigate if passaged redifferentiated chondrocytes in fibrin gel have the ability to form cartilage tissue and if these redifferentiated cells will enhance the formation of hyaline cartilage in vivo when implanted into critical-size osteochondral defects. Study Design: Controlled laboratory study. Methods: Rabbit and human chondrocytes were serially passaged twice in monolayer culture. Twice-passaged cells were used directly (dedifferentiated) or redifferentiated in high-density culture with TGFβ3. Dedifferentiated or redifferentiated cells were mixed with fibrin gel to form fibrin clots, which were cultured in vitro to assess the use of fibrin gel as a scaffold or implanted in vivo in a critical-size osteochondral defect in New Zealand White rabbit knee joints. Rabbits were sacrificed 6 weeks after implantation, and tissues were assessed histologically and by immunohistochemistry. Results: Redifferentiation of passaged chondrocytes by means of 3-dimensional culture in the presence of TGFβ3 improved the formation of cartilaginous tissues in vitro, and culture in fibrin gel did not affect the cell phenotype. Implantation of dedifferentiated cells in vivo resulted in fibrocartilaginous repair tissues. Redifferentiated chondrocyte implants resulted in granulation tissues containing the hyaline cartilage marker collagen type 2. Conclusion: Redifferentiated chondrocytes will maintain their chondrogenic differentiation in fibrin clots. Implanted redifferentiated chondrocytes show a different reparative response than dedifferentiated chondrocytes and do not appear to enhance repair at an early time point. Another study of longer duration is required to assess tissue maturation over time. Clinical Relevance: Redifferentiation of passaged chondrocytes with TGFβ3 before implantation does not improve defect repair in the first 6 weeks.