bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardised approach to measuring goal-based outcomes among older disabled adults: results from a multisite pilot
Authors: Giovannetti Erin R , Clair Catherine A , Jennings Lee A , Sandberg Shana F , Bowman Angelia , Reuben David B , Scholle Sarah H 
Published: October 2020

BackgroundOlder adults with complex care needs face trade-offs in determining the right course of treatment. The Centers for Medicare and Medicaid Services identified ‘Care is personalized and aligned with patient’s goals’ as a key meaningful measures category, yet existing quality measures typically assess disease-specific care and may not effectively evaluate what is most important to older adults and family members. Measures based on individualised goals and goal-based outcomes have been proposed as an alternative but are not routinely assessed or implemented.ObjectivesWe tested two approaches to assessing goal-based outcomes that allow individuals to set goals based on their own priorities and measure progress—(1) goal attainment scaling and (2) existing, validated patient-reported outcome measures (PROM).MethodsA prospective cohort study of feasibility in seven sites (33 clinicians) of the two approaches with 229 individuals. We calculated performance on a measure of achievement of individually identified goals.ResultsBoth approaches were successfully implemented in a non-randomly selected population, and a goal-based outcome could be calculated for 189 (82%) of participants. Most individuals met their goal-based outcome (73%) with no statistical difference between the goal attainment scaling approach (74%) and the patient-reported outcomes approach (70%). Goals were heterogeneous ranging from participating in activities, health management, independence and physical health. Clinicians chose to use goal attainment scaling (n=184, 80%) more often than PROMs (n=49, 20%) and rated the goal attainment scaling approach as useful for providing patient care.ConclusionGoal-based outcomes have the potential to both improve the way healthcare is provided and fill a critical gap in value-based payment.
KALRNmutations promote antitumor immunity and immunotherapy response in cancer
Authors: Li Mengyuan , Ma Yuxiang , Zhong You , Liu Qian , Chen Canping , Qiang Lei , Wang Xiaosheng 
Published: October 2020

Backgroundkalirin RhoGEF kinase (KALRN) is mutated in a wide range of cancers. Nevertheless, the association betweenKALRNmutations and the pathogenesis of cancer remains unexplored. Identification of biomarkers for cancer immunotherapy response is crucial because immunotherapies only show beneficial effects in a subset of patients with cancer.MethodsWe explored the correlation betweenKALRNmutations and antitumor immunity in 10 cancer cohorts from The Cancer Genome Atlas program by the bioinformatics approach. Moreover, we verified the findings from the bioinformatics analysis with in vitro and in vivo experiments. We explored the correlation betweenKALRNmutations and immunotherapy response in five cancer cohorts receiving immune checkpoint blockade therapy.ResultsAntitumor immune signatures were more enriched inKALRN-mutated thanKALRN-wildtype cancers. Moreover,KALRNmutations displayed significant correlations with increased tumor mutation burden and the microsatellite instability or DNA damage repair deficiency genomic properties, which may explain the high antitumor immunity inKALRN-mutated cancers. Also, programmed cell death 1 ligand (PD-L1) expression was markedly upregulated inKALRN-mutated versusKALRN-wildtype cancers. The increased antitumor immune signatures and PD-L1 expression inKALRN-mutated cancers may favor the response to immune checkpoint blockade therapy in this cancer subtype, as evidenced in five cancer cohorts receiving antiprogrammed cell death protein 1 (PD-1)/PD-L1/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immunotherapy. Furthermore, the significant association betweenKALRNmutations and increased antitumor immunity was associated with the fact thatKALRNmutations compromised the function of KALRN in targeting Rho GTPases for the regulation of DNA damage repair pathways. In vitro and in vivo experiments validated the association of KALRN deficiency with antitumor immunity and the response to immune checkpoint inhibitors.ConclusionsTheKALRNmutation is a useful biomarker for predicting the response to immunotherapy in patients with cancer.
Adherent cell depletion promotes the expansion of renal cell carcinoma infiltrating T cells with optimal characteristics for adoptive transfer
Authors: Braun Mitchell W , Abdelhakim Haitham , Li Meizhang , Hyter Stephen , Pessetto Ziyan , Koestler Devin C , Pathak Harsh B , Dunavin Neil , Godwin Andrew K 
Published: October 2020

BackgroundTumor-infiltrating lymphocyte (TIL) therapy is a personalized cancer treatment which involves generating ex vivo cultures of tumor-reactive T cells from surgically resected tumors and administering the expanded TILs as a therapeutic infusion. Phase 1 of many TIL production protocols use aldesleukin (IL-2) alone to establish TIL cultures (termed “PreREP” (Pre-Rapid Expansion Protocol)); however, this fails to consistently produce TIL cultures from renal cell carcinoma (RCC) in a timely manner. Adding mitogenic stimulation via anti-CD3/anti-CD28 beads along with IL-2 to the fresh tumor digest (FTD) during TIL generation (termed “FTD+ beads”) increases successful TIL culture rates; however, T cells produced by this method may be suboptimal for adoptive transfer. We hypothesize that adherent cell depletion (ACD) before TIL expansion will produce a superior TIL product by removing the immunosuppressive signals originating from adherent tumor and stromal cells. Here we investigate if “panning,” a technique for ACD prior to TIL expansion, will impact the phenotype, functionality and/or clonality of ex vivo expanded RCC TILs.MethodsTumor specimens from 55 patients who underwent radical or partial nephrectomy at the University of Kansas Medical Center (KUMC) were used to develop the panning method and an additional 19 specimens were used to validate the protocol. Next-generation sequencing, immunohistochemistry/immunocytochemistry and flow cytometry were used during method development. The phenotype, functionality and clonality of autologous TILs generated in parallel by panning, PreREP, and FTD+ beads were assessed by flow cytometry, in vitro co-culture assays, and TCRB CDR3 sequencing.ResultsTIL cultures were successfully generated using the panning protocol from 15/16 clear cell, 0/1 chromophobe, and 0/2 papillary RCC samples. Significantly fewer regulatory (CD4+/CD25+/FOXP3+) (p=0.049, p=0.005), tissue-resident memory (CD8+/CD103+) (p=0.027, p=0.009), PD-1+/TIM-3+ double-positive (p=0.009, p=0.011) and TIGIT+ T cells (p=0.049, p=0.026) are generated by panning relative to PreREP and FTD+ beads respectively. Critically, a subset of TILs generated by panning were able to degranulate and/or produce interferon gamma in response to autologous tumor cells and the average tumor-reactive TIL yield was greatest when using the panning protocol.ConclusionsRemoving immunosuppressive adherent cells within an RCC digest prior to TIL expansion allow for the rapid production of tumor-reactive T cells with optimal characteristics for adoptive transfer.
Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells
Authors: Russell Dayvia A , Markiewicz Margaret , Oates Jim C 
Published: October 2020

ObjectivesSLE is associated with endothelial cell dysfunction (ECD). Understanding how ECD leads to neutrophil infiltration into glomeruli is essential to finding therapeutic targets for SLE. The aim of this study is to determine the effect of SLE serum from patients with active disease to induce neutrophil adhesion to and chemotaxis towards glomerular endothelial cells and factors induced by serum that associate with neutrophil chemotaxis.MethodsPatients with SLE had serum collected during paired longitudinal visits with lower and higher activity. 13 patients with SLE (5 SLE, 5 SLE with hypertension (HTN) and 3 SLE lupus nephritis (LN) and HTN), and 10 healthy controls (5 with and 5 without HTN) were examined. The adhesion of neutrophils to serum-treated human renal glomerular endothelial cells (HRGECs) or chemotaxis of neutrophils towards conditioned media from serum-treated HRGECs was determined, and levels of cytokines in this conditioned medium were quantified. Pathway analysis of cytokines induced by SLE and LN serum that associated with neutrophil migration was performed.ResultsHRGECs treated with SLE serum induced significantly greater neutrophil chemotaxis and adhesion compared with control serum. When examining specific cohorts, SLE HTN and LN HTN promoted greater neutrophil chemotaxis than control serum, while SLE HTN and LN HTN promoted greater chemotaxis than SLE serum. Serum from active disease visits promoted neutrophil chemotaxis and adhesion over paired inactive visits. Levels of platelet-derived growth factor-BB, interleukin (IL)-15 and IL-8 secreted by SLE serum-treated HRGECs positively correlated with neutrophil chemotaxis. Pathway analysis suggested that LN serum induced pathways important in endoplasmic reticulum and oxidative stress.ConclusionsSLE serum induces expression of mediators by HRGECs that promote neutrophil chemotaxis and adhesion, which increases during disease activity, and associates with factors common to pathways of endoplasmic reticulum and oxidative stress. These findings highlight the potential importance of serum factor-induced ECD in SLE and LN.
Light clusters in dilute heavy-baryon admixed nuclear matter
Authors: Sedrakian Armen 
Published: October 2020

AbstractWe study the composition of nuclear matter at sub-saturation densities, non-zero temperatures, and isospin asymmetry, under the conditions characteristic of binary neutron star mergers, stellar collapse, and low-energy heavy-ion collisions. The composition includes light clusters with mass number $$A\le 4$$

A
≤
4

, a heavy nucleus ($$^{56}{Fe}$$

56

Fe

), the $$\varDelta $$
Δ
-resonances, the isotriplet of pions, as well as the $$\Lambda $$
Λ
hyperon. The nucleonic mean-fields are computed from a zero-range density functional, whereas the pion-nucleon interactions are treated to leading order in chiral perturbation theory. We show that with increasing temperature and/or density the composition of matter shifts from light-cluster to heavy baryon dominated one, the transition taking place nearly independent of the magnitude of the isospin. Our findings highlight the importance of simultaneous treatment of light clusters and heavy baryons in the astrophysical and heavy-ion physics contexts.
Characterization and origin of large Campanian depressions within the Chalk Group of the Danish Central Graben – implications for hydrocarbon exploration and development
Authors: Smit Florian W. H. , Stemmerik Lars , Lüthje Mikael , van Buchem Frans S. P. 
Published: October 2020

Abstract

This study re-examines large and deep U-shaped reflections (2–4 km wide and 100–200 m deep) within the Upper Cretaceous–Danian Chalk Group in the inverted Roar Basin of the Danish North Sea, previously interpreted as a moat associated with a contour-parallel current system and/or erosive channels formed by gravity-driven turbidites. Improved 3D seismic data quality and seismic interpretation techniques helped to identify overlooked reflection terminations, which suggest that rather than a linear depression, the U-shaped reflections outline several bowl-shaped depressions. In addition, vertical high-amplitude columns and vertical discontinuity zones within and below the depressions were recognized and interpreted to indicate the presence of small fluid pipes, suggesting that the formation of the depressions is more complex. Carbon isotope analysis of high acoustic impedance beds within the underlying Lower Cretaceous chalk showed negative δ
13
C values down to −20‰, and are interpreted to indicate sediments influenced by methane-derived authigenic carbonates. Permo-Triassic half-grabens seem to have been a major source of gas-bearing fluids, as evidenced by hydrocarbon leakage phenomena within Triassic–Lower Cretaceous strata. In areas where Zechstein salt is present, the leakage root lies at salt welds, causing the formation of focused seismic reflection wipe-out and dim zones. In areas where salt was absent, the leakage root comprises a much more diffuse zone across the fault boundaries of the Permo-Triassic half-graben, and gas chimneys are characterized seismically as broad vertical dim zones up to 10 km wide. Campanian inversion tectonics caused fault reactivation and several hundreds of metres of uplift in the Roar Basin, which created an instability for the trapped gas-bearing fluids. Gentle fluid venting through observed pipes caused sediment suspension and entrainment, which could be carried away by bottom-current activity, causing localized zones of non-deposition and the formation of individual depressions. This model thus does not disregard the role of bottom-current activity in the formation of the depressions, yet it includes a fluid-venting element that fits better with the architecture and overall evidence for fluid-venting features in pre-chalk strata, as well as in the Chalk Group. Importantly, it shows that prior to the thermogenic maturation of the main source rock (i.e. the Bo Member of the Farsund Formation in the Late Miocene), fluid venting had already occurred on the Late Cretaceous seafloor from deeper source rocks that are at present overmature.
Long‐Term Results After Drug‐Eluting Versus Bare‐Metal Stent Implantation in Saphenous Vein Grafts: Randomized Controlled Trial
Authors: Fahrni Gregor , Farah Ahmed , Engstrøm Thomas , Galatius Søren , Eberli Franz , Rickenbacher Peter , Conen David , Mueller Christian , Pfister Otmar , Twerenbold Raphael , Coslovsky Michael , Cattaneo Marco , Kaiser Christoph , Mangner Norman , Schuler Gerhard , Pfisterer Matthias , Möbius‐Winkler Sven , Jeger Raban V. ,   for the BASKET‐SAVAGE‐Investigators*
Published: October 2020

Background
Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long‐term outcome.

Methods and Results

In this multinational trial, patients were randomized to paclitaxel‐eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target‐vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5‐year follow‐up. One hundred seventy‐three patients were included in the trial (89 DES versus 84 BMS). One‐year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03–0.64,
P
=0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target‐vessel revascularization. Five‐year major adverse cardiac event rates remained lower in the DES compared with the BMS arm (35.5% versus 56.1%, hazard ratio, 0.40; 95% CI, 0.23–0.68,
P
<0.001). A landmark‐analysis from 1 to 5 years revealed a persistent benefit of DES over BMS (hazard ratio, 0.33; 95% CI, 0.13–0.74,
P
=0.007) in terms of target‐vessel revascularization. More patients in the BMS group underwent multiple target‐vessel revascularization procedures throughout the study period compared with the DES group (DES 1.1% [n=1] versus BMS 9.5% [n=8],
P
=0.013). Enrollment was stopped before the target sample size of 240 patients was reached.

Conclusions
In this randomized controlled trial with prospective long‐term follow‐up of up to 5 years, DES showed a better efficacy than BMS with sustained benefits over time. DES may be the preferred strategy in this patient population.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT00595647.
Changes in Extreme Precipitation Accumulations during the Warm Season over Continental China
Authors: Chang Meiyu , Liu Bo , Martinez-Villalobos Cristian , Ren Guoyu , Li Shangfeng , Zhou Tianjun 
Published: October 2020

AbstractPrecipitation accumulations, integrated over rainfall events, are investigated using hourly data across continental China during the warm season (May–October) from 1980 to 2015. Physically, the probability of precipitation accumulations drops slowly with event size up to an approximately exponential cutoff scale sL where probability drops much faster. Hence sL can be used as an indicator of high accumulation percentiles (i.e., extreme precipitation accumulations). Overall, the climatology of sL over continental China is about 54 mm. In terms of cutoff changes, the current warming stage (1980–2015) is divided into two periods, 1980–97 and 1998–2015. We find that the cutoff in 1998–2015 increases about 5.6% compared with that of 1980–97, with an average station increase of 4.7%. Regionally, sL increases are observed over East China (10.9% ± 1.5%), Northwest China (9.7% ± 2.5%), South China (9.4% ± 1.4%), southern Southwest China (5.6% ± 1.2%), and Central China (5.3% ± 1.0%), with decreases over North China (−10.3% ± 1.3%), Northeast China (−4.9% ± 1.5%), and northern Southwest China (−3.9% ± 1.8%). The conditional risk ratios for five subregions with increased cutoff sL are all greater than 1.0, indicating an increased risk of large precipitation accumulations in the most recent period. For high precipitation accumulations larger than the 99th percentile of accumulation s99, the risk of extreme precipitation over these regions can increase above 20% except for South China. These increases of extreme accumulations can be largely explained by the extended duration of extreme accumulation events, especially for “extremely extreme” precipitation greater than s99.
Text messages to reduce depressive symptoms: Do they work and what makes them effective? A systematic review
Authors: Cox Katherine L , Allida Sabine M , Hackett Maree L 
Published: October 2020

Objective: In this systematic review and meta-analysis, we aimed to quantify the effects of text messaging interventions to reduce depressive symptoms and identify variables that might influence the effectiveness of the intervention. Design: Electronic databases including EMBASE, CENTRAL, MEDLINE, CINAHL, PsycINFO and SCOPUS, as well as Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) were searched for randomised controlled trials that sent one or more text messages with health-related content to adults who had been identified by a healthcare provider. Results: Seven trials (nine comparisons), with 1,918 participants, were included in the review, and the pooled analysis revealed a borderline statistically significant reduction in depressive symptom scores between the text messaging intervention and control groups (standardised mean difference [SMD], −0.27; 95% confidence interval [CI], −0.54 to 0.00; p = .00) favouring intervention at the end. Statistically significant reductions were shown in important subgroups, for example, where the primary aim of the messages was to reduce depressive symptoms; in those using the Beck Depression Inventory (BDI) or 9-item Patient Health Questionnaire (PHQ-9) questionnaires; where text message content was targeted at mental well-being, mood improvement and cognitive behavioural therapy information; and when the message frequency was ⩾2 times per week. Conclusion: Text messaging has potential to reduce depressive symptoms. The results of this review should be interpreted with caution, however, due to the methodological limitations of included trials. More research is required before recommendations can be made about the routine use of text messaging for the management of depressive symptoms.
Climate Change, Neoliberalism, and Migration: Mexican Sons of Peasants on the Beach
Authors: Wilson Tamar Diana 
Published: October 2020

Climate change and neoliberal policies in Mexico have been fomenting migration by campesinos and their sons. This migration is primarily internal, to cities and tourist centers, where migrants engage in informal and semi-informal income-generating activities. Interviews with 32 beach vendors, sons of campesinos, in Cabo San Lucas reflect these two drivers of migration: while most reported that they would like to farm, they identified drought and lack of government aid as major difficulties for farmers in their hometowns. El cambio climático y las políticas neoliberales en México han fomentado la migración de campesinos y sus hijos. Esta migración mayoritariamente interna se dirige a ciudades y centros turísticos, donde los migrantes participan en actividades informales y semiformales para generar ingresos. Entrevistas con 32 vendedores de playa en Cabo San Lucas, todos ellos hijos de campesinos, reflejan el efecto de los mencionados impulsores migración: aunque la mayoría de los entrevistados informó que le gustaría cultivar sus tierras, la sequía y la falta de apoyo gubernamental se mencionaron como dos grandes obstáculos a la agricultura en sus lugares de origen.
Paternal exposure to morphine during adolescence potentiates morphine withdrawal in male offspring: Involvement of the lateral paragigantocellularis nucleus
Authors: Azadi Maryam , Gompf Heinrich S , Azizi Hossein 
Published: October 2020

Background: Opiate exposure during adolescence perturbs the brain’s maturation process and potentially confers long-term adverse consequences, not only in exposed individuals but also in their posterity. Here, we investigate the outcomes of adolescent paternal morphine exposure on morphine withdrawal profile in male offspring. Methods: Male Wistar rats were chronically subjected to 10 days of an escalating regimen of morphine during adolescence. After a 20-day washout period, adult males were allowed to copulate with naïve females. The adult male offspring were tested for somatic and affective components of naloxone-precipitated morphine withdrawal using conditioned place aversion. Moreover, electrical activity of the lateral paragigantocellularis (LPGi) nucleus, which is involved in development of opiate dependence, was recorded in response to a challenge dose of morphine via extracellular single-unit recordings. Results: Morphine-sired offspring exhibited augmented expression of naloxone-induced somatic and affective signs of opiate withdrawal compared to the control saline-sired counterparts. In vivo recording revealed that LPGi neurons displayed heterogeneous responses (inhibitory, excitatory, and no change) to acute morphine administration in both morphine- and saline-sired animals. The morphine-induced discharge inhibition was potentiated in morphine-sired offspring. However, the extent of discharge excitation in response to morphine did not reach significance in these subjects. Moreover, the lack of alteration in maternal behavior toward morphine-sired offspring indicates that this is due to germline-dependent transmission of epigenetic traits across generations. Conclusions: Preconception paternal exposure to morphine during adolescence potentiates opiate withdrawal signs in male offspring which is mediated, at least in part, by epigenetic alteration of LPGi-related brain circuitry.