bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines and costimulation in acute graft-versus-host disease
Authors: Hill Geoffrey R. , Koyama Motoko 
Published: June 2020

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) is an important curative therapy for high-risk hematological malignancies, but the development of severe and/or steroid-refractory acute graft-versus-host disease (aGVHD) remains a significant limitation to optimal outcomes. New approaches to prevent and treat aGVHD remain an unmet need that can be best addressed by understanding the complex disease pathophysiology. It is now clear that chemoradiotherapy used prior to alloSCT induces the release of endogenous alarmins (eg, HMGB-1, ATP, IL-1α, IL-33) from recipient tissue. Exogenous pathogen-derived molecules (eg, lipopolysaccharide, nucleic acids) also translocate from the gastrointestinal tract lumen. Together, these danger signals activate antigen-presenting cells (APCs) to efficiently present alloantigen to donor T cells while releasing cytokines (eg, interleukin-12 [IL-12], IL-23, IL-6, IL-27, IL-10, transforming growth factor-β) that expand and differentiate both pathogenic and regulatory donor T cells. Concurrent costimulatory signals at the APC–T-cell interface (eg, CD80/CD86-CD28, CD40-CD40L, OX40L-OX40, CD155/CD112-DNAM-1) and subsequent coinhibitory signals (eg, CD80/CD86-CTLA4, PDL1/2-PD1, CD155/CD112-TIGIT) are critical to the acquisition of effector T-cell function and ensuing secretion of pathogenic cytokines (eg, IL-17, interferon-γ, tissue necrosis factor, granulocyte-macrophage colony-stimulating factor) and cytolytic degranulation pathway effectors (eg, perforin/granzyme). This review focuses on the combination of cytokine and costimulatory networks at the T-cell surface that culminates in effector function and subsequent aGVHD in target tissue. Together, these pathways now represent robust and clinically tractable targets for preventing the initiation of deleterious immunity after alloSCT.
Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease
Authors: Toubai Tomomi , Magenau John 
Published: June 2020

AbstractAcute graft-versus-host disease (GVHD) is 1 of the major life-threating complications after allogeneic cell transplantation. Although steroids remain first-line treatment, roughly one-half of patients will develop steroid-refractory GVHD (SR-GVHD), which portends an extremely poor prognosis. Many agents that have shown encouraging response rates in early phase 1/2 trials for prevention and treatment have been unsuccessful in demonstrating a survival advantage when applied in the setting of SR-GVHD. The discovery of novel treatments has been further complicated by the absence of clinically informative animal models that address what may reflect a distinct pathophysiology. Nonetheless, the combined knowledge of established bone marrow transplantation models and recent human trials in SR-GVHD patients are beginning to illuminate novel mechanisms for inhibiting T-cell signaling and promoting tissue tolerance that provide an increased understanding of the underlying biology of SR-GVHD. Here, we discuss recent findings of newly appreciated cellular and molecular mechanisms and provide novel translational opportunities for advancing the effectiveness of treatment in SR-GVHD.
Device-measured sedentary behavior and physical activity in older adults differ by demographic and health-related factors
Authors: Dohrn Ing-Mari , Gardiner Paul A. , Winkler Elisabeth , Welmer Anna-Karin 
Published: June 2020

Abstract
Background
Our aim was to describe and explore older adults’ device-measured sedentary behavior and physical activity (PA) pattern by sex, age, education, marital status, body mass index, and physical function; and to assess agreement regarding fulfillment of PA recommendations, i.e. 150 min/week of moderate-to-vigorous intensity PA (MVPA), between device-measured and self-reported PA.

Method
We included 656 older adults (64% women), aged 66, 81–87 or ≥ 90 years from a Swedish population-based cohort study. The activPAL3 accelerometer provided information on sedentary behavior (sedentary time, sedentary bouts, sit-to-stand transitions) and PA. Stepping ≥100 steps/min was considered MVPA; standing and stepping < 100 steps/min were considered light-intensity PA (LPA). Self-reported PA was compared with min/week in MVPA and steps/day.

Results
On average, 60% of wear time was spent sedentary, 36% in LPA, and 4% in MVPA. Relative to men, women, had significantly (p < 0.05) more sit-to-stand transitions, spent 33 min/day less sedentary and 27 min/day more in LPA, and were more likely to report meeting PA recommendations, but showed no difference in steps/day, MVPA, or sedentary bout duration. Older age was associated with more sedentary time, lower MVPA and fewer steps/day. The prevalence of meeting PA recommendations was 59% device-measured and 88% by self-report with limited agreement between methods (Cohen’s Kappa = 0.21, Spearman’s rho = 0.28). Age differences were much more pronounced with objective measures than by self-report.

Conclusions
We found significant sex differences in sedentary behavior and time in LPA in older adults, but not in MVPA, in contrast to previous findings. Sedentary time increased with age, with small differences in accumulation pattern. MVPA time was lower with older age, obesity, and poor physical function. A majority of the participants > 80 years did not meet the PA recommendations. Given the strong relationships between sedentary behavior, PA and health in older adults, programs are needed to address these behaviors. Agreement between device-measured and self-reported fulfillment of PA recommendations was limited. Device-based measurement adds value to PA studies, providing richer and different data than self-report.
Genome-wide identification and characterization of cucumber bHLH family genes and the functional characterization of CsbHLH041 in NaCl and ABA tolerance in Arabidopsis and cucumber
Authors: Li Jialin , Wang Ting , Han Jing , Ren Zhonghai 
Published: June 2020

Abstract
Background
The basic/helix-loop-helix (bHLH) transcription factor family exists in all three eukaryotic kingdoms as important participants in biological growth and development. To date, the comprehensive genomic and functional analyses of bHLH genes has not been reported in cucumber (Cucumis sativus L.).

Results
Here, a total of 142 bHLH genes were identified and classified into 32 subfamilies according to the conserved motifs, phylogenetic analysis and gene structures in cucumber. The sequences of CsbHLH proteins were highly conserved based on the results of multiple sequence alignment analyses. The chromosomal distribution, synteny analysis, and gene duplications of these 142 CsbHLHs were further analysed. Many elements related to stress responsiveness and plant hormones were present in the promoter regions of CsbHLH genes based on a cis-element analysis. By comparing the phylogeny of cucumber and Arabidopsis bHLH proteins, we found that cucumber bHLH proteins were clustered into different functional clades of Arabidopsis bHLH proteins. The expression analysis of selected CsbHLHs under abiotic stresses (NaCl, ABA and low-temperature treatments) identified five CsbHLH genes that could simultaneously respond to the three abiotic stresses. Tissue-specific expression profiles of these five genes were also analysed. In addition, 35S:CsbHLH041 enhanced the tolerance to salt and ABA in transgenic Arabidopsis and in cucumber seedlings, suggesting CsbHLH041 is an important regulator in response to abiotic stresses. Lastly, the functional interoperability network among the CsbHLH proteins was analysed.

Conclusion
This study provided a good foundation for further research into the functions and regulatory mechanisms of CsbHLH proteins and identified candidate genes for stress resistance in cucumber.
The growing impact of older patients in the emergency department: a 5-year retrospective analysis in Brazil
Authors: Gomes João Carlos Pereira , Dias Roger Daglius , de Barros Jacson Venancio , Velasco Irineu Tadeu , Jacob Filho Wilson 
Published: June 2020

Abstract
Background
The average age of the global population is rising at an increasing rate. There is a disproportional increase in Emergency Department (ED) visits by older people worldwide. In the Brazilian health system, complex and severely ill patients and those requiring specialized urgent procedures are referred to tertiary level care. As far as we know, no other study in Latin America has analyzed the impact of demographic changes in tertiary ED attendance. Aim: To describe the sociodemographic characteristics and outcomes of tertiary Brazilian ED users.

Methods
Design: Observational cross-sectional analytic study. Setting: Emergency Department, tertiary university hospital, São Paulo, Brazil. Participants: patients aged 18 years or older attending a tertiary ED (2009–2013). The primary outcomes were hospitalization and mortality; the secondary outcome was ICU admission. Age was categorized as ‘young adults’ (18-39y), ‘adults’ (40-59y), ‘young-older adults’ (60-79y), and ‘old-older adults’ (80-109y). Other variables included sex, reason for attendance, time of ED visit, mode of presentation, type of hospitalization, main procedure, length of hospital stay (LOS) and length of ICU stay (ICU-LOS). We calculated descriptive statistics, built generalized linear mixed models for each outcome and estimated Odds Ratios (95% CI) for the independent categorical variables. The significance level was 5% with Bonferroni correction.

Results
Older age-groups represented 26.6% of 333,028 ED visits, 40.7% of admissions, 42.7% of ICU admissions and 58% of all deaths. Old-older patients accounted for 5.1% of ED visits, 9.5% of admissions and 10.1% of ICU admissions. Hospitalization, ICU admission and mortality rates increased with older age in both sexes. LOS and ICU-LOS were similar across age-groups. The proportions of visits and admissions attributed to young adults decreased annually, while those of people aged 60 or over increased. The ORs for hospitalization, ICU admission and mortality associated with the old-older group were 3.49 (95% CI = 3.15–3.87), 1.27 (1.15–1.39) and 5.93 (5.29–6.66) respectively, with young adults as the reference.

Conclusions
In tertiary ED, age is an important risk factor for hospitalization and mortality, but not for ICU admission. Old-older people are at the greatest risk and demand further subgroup stratification.
Challenges of recruiting emergency department patients to a qualitative study: a thematic analysis of researchers’ experiences
Authors: Price Delyth , Edwards Michelle , Carson-Stevens Andrew , Cooper Alison , Davies Freya , Evans Bridie , Hibbert Peter , Hughes Thomas , Rainer Tim , Siriwardena Niro , Edwards Adrian 
Published: June 2020

Abstract
Background
At times of increasing pressure on emergency departments, and the need for research into different models of service delivery, little is known about how to recruit patients for qualitative research in emergency departments. We report from one study which aimed to collect evidence on patients’ experiences of attending emergency departments with different models of using general practitioners, but faced challenges in recruiting patients. This paper aims to identify and reflect on the challenges faced at all stages of patient recruitment, from identifying and inviting eligible patients, consenting them for participation and finally to engaging them in interviews, and make recommendations based on our learning.

Methods
A thematic analysis was carried out on field-notes taken during research visits and meeting minutes of discussions to review and improve patient recruitment throughout the study.

Results
The following factors influenced the success of patient recruitment in the emergency department setting: complicated or time-consuming electronic health record systems for identifying patients; narrow participant eligibility criteria; limited research nurse support; and lack of face-to-face communication between researchers and eligible patients.

Conclusions
This paper adds to the methodological evidence for improving patient recruitment in different settings, with a focus on qualitative research in emergency departments. Our findings have implications for future studies attempting to recruit patients in similar settings.
Readmission of older acutely admitted medical patients after short-term admissions in Denmark: a nationwide cohort study
Authors: Klinge M. , Aasbrenn M. , Öztürk B. , Christiansen C. F. , Suetta C. , Pressel E. , Nielsen F. E. 
Published: June 2020

Abstract
Background
Knowledge of unplanned readmission rates and prognostic factors for readmission among older people after early discharge from emergency departments is sparse. The aims of this study were to examine the unplanned readmission rate among older patients after short-term admission, and to examine risk factors for readmission including demographic factors, comorbidity and admission diagnoses.

Methods
This cohort study included all medical patients aged ≥65 years acutely admitted to Danish hospitals between 1 January 2013 and 30 June 2014 and surviving a hospital stay of ≤24 h. Data on readmission within 30 days, comorbidity, demographic factors, discharge diagnoses and mortality were obtained from the Danish National Registry of Patients and the Danish Civil Registration System. We examined risk factors for readmission using a multivariable Cox regression to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for readmission.

Results
A total of 93,306 patients with a median age of 75 years were acutely admitted and discharged within 24 h, and 18,958 (20.3%; 95% CI 20.1 - 20.6%) were readmitted with a median time to readmission of 8 days (IQR 3 - 16 days). The majority were readmitted with a new diagnosis. Male sex (aHR 1.15; 1.11 - 1.18) and a Charlson Comorbidity Index ≥3 (aHR 2.28; 2.20 - 2.37) were associated with an increased risk of readmission. Discharge diagnoses associated with increased risk of readmission were heart failure (aHR 1.26; 1.12 - 1.41), chronic obstructive pulmonary disease (aHR 1.33; 1.25 - 1.43), dehydration (aHR 1.28; 1.17 - 1.39), constipation (aHR 1.26; 1.14 - 1.39), anemia (aHR 1.45; 1.38 - 1.54), pneumonia (aHR 1.15; 1.06 - 1.25), urinary tract infection (aHR 1.15; 1.07 - 1.24), suspicion of malignancy (aHR 1.51; 1.37 - 1.66), fever (aHR 1.52; 1.33 - 1.73) and abdominal pain (aHR 1.12; 1.05 - 1.19).

Conclusions
One fifth of acutely admitted medical patients aged ≥65 were readmitted within 30 days after early discharge. Male gender, the burden of comorbidity and several primary discharge diagnoses were risk factors for readmission.
Cryptococcal antigenemia and its predictors among HIV infected patients in resource limited settings: a systematic review
Authors: Derbie Awoke , Mekonnen Daniel , Woldeamanuel Yimtubezinash , Abebe Tamrat 
Published: June 2020

Abstract
Background
Cryptococcosis is an opportunistic fungal infection that primarily affects people with advanced HIV/AIDS and is an important cause of morbidity and mortality around the globe. By far the most common presentation of the disease is cryptococcal meningitis (CM), which leads to an estimated 15–20% of all HIV related deaths worldwide, 75% of which are in sub-Saharan Africa. However, to the best of our knowledge there is quite limited reviewed data on the epidemiology of cryptococcal antigenemia in a large HIV-infected population in resource limited settings.

Methods
Articles published in English irrespective of the time of publication were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. In addition, Google Scholar and Google databases were searched manually for grey literature. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. The pooled prevalence of cryptococcal antigenemia was determined with 95% confidence interval (CI).

Results
Among 2941 potential citations, we have included 22 studies with a total of 8338 HIV positive individuals. The studies were reported in ten different countries during the year (2007–2018). Most of the articles reported the mean CD4 count of the participants below 100 cells/μl. The pooled prevalence of cryptococcal antigenemia at different CD4 count and ART status was at 8% (95%CI: 6–10%) (ranged between 1.7 and 33%). Body mass index (BMI) < 18.5 kg/m2, CD4 count < 100 cells, patients presenting with headache and male gender were reported by two or more articles as an important predictors of cryptococcal antigenemia.

Conclusions
Implementing a targeted screening of HIV patients with low BMI, CD4 count < 100 cells, having headache and males; and treatment for asymptomatic cryptococcal disease should be considered. Additional data is needed to better define the epidemiology of cryptococcal antigenemia and its predictors in resource limited settings in order to optimize the prevention, diagnosis, and treatment strategies.
Double-carbapenem therapy in the treatment of multidrug resistant Gram-negative bacterial infections: a systematic review and meta-analysis
Authors: Li Yuan-yuan , Wang Jin , Wang Rui , Cai Yun 
Published: June 2020

Abstract
Background
To compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections.

Methods
Cochrane Library, PubMed, Embase and Web of Science as well as Chinese databases were searched from database establishment to February 2019. All types of studies were included if they had evaluated efficacy and safety of DCT regimens in patients with MDR Gram-negative bacterial infections. Clinical response, microbiological response, adverse events and mortality were the main outcomes. The protocol was registered with PROSPERO No. CRD42019129979.

Results
Three cohort or case-control studies consisting of 235 patients and 18 case series or case reports consisting of 90 patients were included. The clinical and microbiological responses were similar between DCT and other regimens in patients with carbapenem-resistant Enterobacteriaceae (CRE) infection. DCT achieved a lower mortality than comparators in patients with CRE infection (OR = 0.44, 95% CI = 0.24–0.82, P = 0.009). Ertapenem was the most reported antibiotic in DCT regimens in case series or case reports. Moreover, clinical and microbiological improvements were found in 59 (65.6%) and 63 (70%) in total 90 cases, respectively.

Conclusions
DCT was as effective as other antibiotics in treating MDR Gram-negative bacterial infections, with similar efficacy response and lower mortality. DCT could be an alternative therapeutic option in the treatment of MDR Gram-negative bacterial infections. High-quality randomized controlled trials were required to confirm the beneficial effects of DCT.
Alignment of preferences in the treatment of multiple myeloma – a discrete choice experiment of patient, carer, physician, and nurse preferences
Authors: Fifer Simon J. , Ho Kerrie-Anne , Lybrand Sean , Axford Laurie J. , Roach Steve 
Published: June 2020

Abstract
Background
Multiple Myeloma (MM) is a cancer characterised by the proliferation of malignant plasma cells in the bone marrow. This study examined the treatment preferences of people living with MM compared to the treatment preferences of other groups involved in treatment decision making, including carers, as well as physicians and nurses who treat people living with MM in Australia.

Methods
Data were collected using discrete choice experiments (DCEs) through an online survey. The DCEs presented participants with a traditional treatment generic choice experiment (e.g., treatment A vs treatment B), focusing on the clinical benefits of treatments and the associated risks. The attributes and levels of the attributes were selected based on previous research, literature review, qualitative research and expert opinion. The DCE data were modelled using a Latent Class Model (LCM).

Results
The model revealed significant heterogeneity in preferences for treatment attributes. In particular, overall survival, remission period and annual out of pocket cost were the attributes with the most variation. In comparison to people living with MM, carers were less cost-sensitive and more concerned with quality of life (remission period). Physicians and nurses were generally more concerned with overall survival and more cost sensitive than people living with MM.

Conclusions
This study demonstrated that not all people living with MM valued the same treatment attributes equally. Further, not all groups involved in MM treatment decision making had preference alignment on all treatment attributes. This has important implications for healthcare policy decisions and shared decision making. Results from this study could be used to guide decisions around the value of new MM medicines or the medical plan surrounding the needs of those living with MM, as well as those caring for them.
Clinical safety and efficacy of a hydrophilic acrylic intraocular lens in a real-world population: a 1-year follow-up retro-prospective study
Authors: Johansson Björn , Daniel Ana C. S. , Herbers Claudia , Gerl Matthias , Kretz Florian T. A. 
Published: June 2020

Abstract
Background
This multicentre, retro-prospective real-world study evaluated the visual, refractive and safety outcomes of a monofocal lens 1 year after implantation in cataract patients with or without pre-existing ocular pathologies.

Methods
Records from 4 centres in Germany and Sweden were reviewed to select eyes with aged-related cataracts, having undergone crystalline lens extraction by phacoemulsification and implantation of a CT ASPHINA 409 IOL. Preoperative, 1-month and 3-month postoperative data was collected retrospectively. In addition, included patients attended a prospective visit 12 months or later after surgery. The examination included: monocular uncorrected (UDVA) and corrected distance visual acuity (CDVA), subjective refraction, slit-lamp examination, optical biometry, intraocular pressure (IOP), endothelial cell count and postoperative complications.

Results
282 eyes, including 94 with pre-existing ocular pathologies, were analysed. Twelve months after the surgery, 95% of eyes achieved monocular CDVA equal or better than 0.3 logMAR, mean postoperative CDVA was 0.06 ± 0.17 logMAR, and mean UDVA 0.31 ± 0.29 logMAR. Visual acuity outcomes were better in eyes with no pre-existing ocular pathologies, but both groups showed a statistically significant improvement after surgery compared with preoperative values (p ≤ 0.002). The mean sphere and spherical equivalent values also improved significantly postoperatively (p = 0.003). Overall, 62.1% of eyes had spherical equivalent within ±0.5 D and 80.9% within ±1.0 D. The IOL was stable in the capsular bag as demonstrated by tilt and decentration measurements. IOP, corneal status, and endothelial cell count values were in the normal range. Nd:YAG treatment was performed on 9.9% of the eyes.

Conclusion
The implantation of the monofocal CT ASPHINA 409 IOL was beneficial to restore vision in eyes with or without concomitant ocular pathology such as macular degeneration, glaucoma, Sicca syndrome, epiretinal membrane, cornea guttata, or amblyopia. Good to excellent long-term visual and refractive outcomes, and a low rate of complications in both healthy and pathological eyes were found 12 months after the surgery.

Trial registration
Trial registered on under the identification NCT03145103 (date of registration 9 May 2017).