bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapidly expanded partially HLA DRB1–matched fungus-specific T cells mediate in vitro and in vivo antifungal activity
Authors: Castellano-González Gloria , McGuire Helen M. , Luciani Fabio , Clancy Leighton E. , Li Ziduo , Avdic Selmir , Hughes Brendan , Singh Mandeep , Fazekas de St Groth Barbara , Renga Giorgia , Pariano Marilena , Bellet Marina M. , Romani Luigina , Gottlieb David J. 
Published: July 2020

Abstract
Invasive fungal infections are a major cause of disease and death in immunocompromised hosts, including patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Recovery of adaptive immunity after HSCT correlates strongly with recovery from fungal infection. Using initial selection of lymphocytes expressing the activation marker CD137 after fungal stimulation, we rapidly expanded a population of mainly CD4+ T cells with potent antifungal characteristics, including production of tumor necrosis factor α, interferon γ, interleukin-17, and granulocyte-macrophage colony stimulating factor. Cells were manufactured using a fully good manufacturing practice–compliant process. In vitro, the T cells responded to fungal antigens presented on fully and partially HLA-DRB1 antigen–matched presenting cells, including when the single common DRB1 antigen was allelically mismatched. Administration of antifungal T cells lead to reduction in the severity of pulmonary and cerebral infection in an experimental mouse model of Aspergillus. These data support the establishment of a bank of cryopreserved fungus-specific T cells using normal donors with common HLA DRB1 molecules and testing of partially HLA-matched third-party donor fungus-specific T cells as a potential therapeutic in patients with invasive fungal infection after HSCT.
T-cell lymphoblastic lymphoma and leukemia: different diseases from a common premalignant progenitor?
Authors: Kroeze Emma , Loeffen Jan L. C. , Poort Vera M. , Meijerink Jules P. P. 
Published: July 2020

Abstract
T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) represent malignancies that arise from the transformation of immature precursor T cells. Similarities in T-LBL and T-ALL have raised the question whether these entities represent 1 disease or reflect 2 different diseases. The genetic profiles of T-ALL have been thoroughly investigated over the last 2 decades, whereas fairly little is known about genetic driver mutations in T-LBL. Nevertheless, the comparison of clinical, immunophenotypic, and molecular observations from independent T-LBL and T-ALL studies lent strength to the theory that T-LBL and T-ALL reflect different presentations of the same disease. Alternatively, T-LBL and T-ALL may simultaneously evolve from a common malignant precursor cell, each having their own specific pathogenic requirements or cellular dependencies that differ among stroma-embedded blasts in lymphoid tissues compared with solitary leukemia cells. This review aims to cluster recent findings with regard to clinical presentation, genetic predisposition, and the acquisition of additional mutations that may give rise to differences in gene expression signatures among T-LBL and T-ALL patients. Improved insight in T-LBL in relation to T-ALL may further help to apply confirmed T-ALL therapies to T-LBL patients.
Noncanonical type 2B von Willebrand disease associated with mutations in the VWF D′D3 and D4 domains
Authors: Sacco Monica , Lancellotti Stefano , Ferrarese Mattia , Bernardi Francesco , Pinotti Mirko , Tardugno Maira , De Candia Erica , Di Gennaro Leonardo , Basso Maria , Giusti Betti , Papi Massimiliano , Perini Giordano , Castaman Giancarlo , De Cristofaro Raimondo 
Published: July 2020

Abstract
We observed a 55-year-old Italian man who presented with mucosal and cutaneous bleeding. Results of his blood analysis showed low levels of von Willebrand factor (VWF) antigen and VWF activity (both VWF ristocetin cofactor and VWF collagen binding), mild thrombocytopenia, increased ristocetin-induced platelet aggregation, and a deficiency of high-molecular-weight multimers, all typical phenotypic hallmarks of type 2B von Willebrand disease (VWD). The analysis of the VWF gene sequence revealed heterozygous in cis mutations: (1) c.2771G&gt;A and (2) c.6532G&gt;T substitutions in the exons 21 and 37, respectively. The first mutation causes the substitution of an Arg residue with a Gln at position 924, in the D′D3 domain. The second mutation causes an Ala to Ser substitution at position 2178 in the D4 domain. The patient’s daughter did not present the same fatherly mutations but showed only the heterozygous polymorphic c.3379C&gt;T mutation in exon 25 of the VWF gene causing the p.P1127S substitution, inherited from her mother. The in vitro expression of the heterozygous in cis VWF mutant rVWFWT/rVWF924Q-2178S confirmed and recapitulated the ex vivo VWF findings. Molecular modeling showed that these in cis mutations stabilize a partially stretched and open conformation of the VWF monomer. Transmission electron microscopy and atomic force microscopy showed in the heterozygous recombinant form rVWFWT/rVWF924Q-2178S a stretched conformation, forming strings even under static conditions. Thus, the heterozygous in cis mutations 924Q/2178S promote conformational transitions in the VWF molecule, causing a type 2B–like VWD phenotype, despite the absence of typical mutations in the A1 domain of VWF.
Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation
Authors: Guo Yaxin , Gu Dan , Huang Tingting , Cao Liyan , Zhu Xinyu , Zhou Yi , Wang Kangru , Kang Xilong , Meng Chuang , Jiao Xinan , Pan Zhiming 
Published: July 2020

Abstract
Background
Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. Given that the inflammasomes play an essential role in resisting bacterial infection, Salmonella has evolved various strategies to regulate activation of the inflammasome, most of which largely remain unclear.

Results
A transposon mutant library in SE strain C50336 was screened for the identification of the potential factors that regulate inflammasome activation. We found that T3SS-associated genes invC, prgH, and spaN were required for inflammasome activation in vitro. Interestingly, C50336 strains with deletion or overexpression of Dam were both defective in activation of caspase-1, secretion of IL-1β and phosphorylation of c-Jun N-terminal kinase (Jnk). Transcriptome sequencing (RNA-seq) results showed that most of the differentially expressed genes and enriched KEGG pathways between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups overlapped, which includes multiple signaling pathways related to the inflammasome. C50336Δdam and C50336::dam were both found to be defective in suppressing the expression of several anti-inflammasome factors. Moreover, overexpression of Dam in macrophages by lentiviral infection could specifically enhance the activation of NLRP3 inflammasome independently via promoting the Jnk pathway.

Conclusions
These data indicated that Dam was essential for modulating inflammasome activation during SE infection, there were complex and dynamic interplays between Dam and the inflammasome under different conditions. New insights were provided about the battle between SE and host innate immunological mechanisms.
Interaction between lipoprotein (a) levels and body mass index in first incident acute myocardial infarction
Authors: Teng Ruo-Ling , Wang Heng , Sun Bei-Chen , Cai Dong-Ping , He Yong-Ming 
Published: July 2020

Abstract
Background
Possible interaction between Lipoprotein (a) (Lp(a)) and body mass index (BMI) was investigated with regard to the risk of first incident acute myocardial infarction (AMI).

Methods
Cross-sectional study of 1522 cases with initial AMI and 1691 controls without coronary artery disease (CAD) were retrospectively analyzed using logistic regression model. Subjects were categorized based on Lp(a) and BMI and compared with regard to occurrence of AMI by calculating odds ratios (ORs) with 95% confidence intervals (CIs). A potential interaction between Lp(a) and BMI was evaluated by the measures of effect modification on both additive (Relative excess risk due to interaction, RERI) and multiplicative scales.

Results
Compared with reference group (BMI < 24 kg/m2 and in the first quintile of Lp(a)), multivariable-adjusted analysis revealed that ORs(95%CI) of AMI were 2.27(1.46–3.52) for higher BMI alone; 1.79(1.11–2.90), 1.65(1.05–2.60), 1.96(1.20–3.20) and 2.34(1.47–3.71) for higher Lp(a) alone across its quintiles; and 2.86(1.85–4.40), 3.30(2.14–5.11), 4.43(2.76–7.09) and 5.98(3.72–9.60) for both higher BMI and higher Lp(a), greater than the sum of the both risks each. Prominent interaction was found between Lp(a) and BMI on additive scale (RERI = 2.45 (0.36–4.54) at the fifth quintile of Lp(a)) but not on multiplicative scale.

Conclusions
This study demonstrates that BMI and Lp(a) levels are important factors affecting the risk of AMI. Significant interaction is found between Lp(a) and BMI in initial AMI on additive scale, indicating that Lp(a) confers greater risk for initial AMI when BMI is elevated. For those whose BMIs are inadequately controlled, Lp(a) lowering may be an option.

Trial registration
This clinical study was not registered in a publicly available registry because this study was a retrospective study first started in 2015. Data are available via the correspondent.
Multimorbidity and consultation time: a systematic review
Authors: Tadeu Ana Carolina Reis , e Silva Caetano Inês Rosendo Carvalho , de Figueiredo Inês Jorge , Santiago Luiz Miguel 
Published: July 2020

Abstract
Background
Multimorbidity (MM) is one of the major challenges health systems currently face. Management of time length of a medical consultation with a patient with MM is a matter of concern for doctors.

Methods
A systematic review was performed to describe the impact of MM on the average time of a medical consultation considering the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The systematic online searches of the Embase and PubMed databases were undertaken, from January 2000 to August 2018. The studies were independently screened by two reviewers to decide which ones met the inclusion criteria. (Kappa = 0.84 and Kappa = 0.82). Differing opinions were solved by a third person. This systematic review included people with MM criteria as participants (two or more chronic conditions in the same individual). The type of outcome included was explicitly defined – the length of medical appointments with patients with MM. Any strategies aiming to analyse the impact of MM on the average consultation time were considered. The length of time of medical appointment for patients without MM was the comparator criteria. Experimental and observational studies were included.

Results
Of 85 articles identified, only 1 observational study was included, showing a clear trend for patients with MM to have longer consultations than patients without MM criteria (p < 0.001).

Conclusions
More studies are required to better assess allocation length-time for patients with MM and to measure other characteristics like doctors’ workload.
Sarcopenia is associated with insomnia in Japanese older adults: a cross-sectional study of data from the Nagasaki Islands study
Authors: Nagaura Yuki , Kondo Hideaki , Nagayoshi Mako , Maeda Takahiro 
Published: July 2020

Abstract
Background
Sarcopenia is associated with increased mortality among older adults. Sleep-related problems have been studied as factors related to sarcopenia. This study was conducted to determine the relationship between sleep-related problems and sarcopenia among Japanese community-dwelling older adults using data from the Nagasaki Islands Study.

Methods
This cross-sectional study analyzed data collected from 2017 to 2018. A total of 1592 older adults (575 men, 36.1%) aged 65 years or older participated. Sarcopenia was evaluated using the skeletal muscle mass index and grasp powers based on the criteria of the Asian Working Group for Sarcopenia. Odds ratios for sarcopenia were calculated using logistic regression analysis. Furthermore, subgroup analysis was performed based on the following tertiles of age: 65–70 years, 71–78 years, and 79–98 years.

Results
The number of participants with sarcopenia was 238 (14.9%). The median age of participants in the sarcopenia group (80 years; interquartile range: 74–84) was significantly higher than in the non-sarcopenia group (73 years; interquartile range 69–79; P <  0.001). In the sarcopenia group, 70.9% of participants had difficulty initiating and/or maintaining sleep, sleep duration tended to be longer (P <  0.001), and 33.3% of participants’ sleep duration was over 9 h. In a logistic regression analysis for sarcopenia, advancing age was the most prominent factor, and the adjusted odds ratio (95% confidence interval) of facing difficulty initiating and/or maintaining sleep was 1.60 (1.14–2.25). Despite longer sleep duration being a significant factor in the univariable analysis, it was not significant in the multivariable analysis. In the logistic regression analysis for sarcopenia among older adults aged 79–98 years, the odds ratio (95% confidence interval) among women was significantly low at 0.53 (0.33–0.83).

Conclusions
Sarcopenia is associated with difficulty initiating and/or maintaining sleep among Japanese older adults. In sarcopenia control measures, sleep/wake disorders related to insomnia are required to be evaluated in detail to help inform nursing and medical policy.
Is adiposity associated with objectively measured physical activity and sedentary behaviors in older adults?
Authors: Zhu Wenfei , Cheng Zhiwei , Howard Virginia J. , Judd Suzanne E. , Blair Steven N. , Sun Yuliang , Hooker Steven P. 
Published: July 2020

Abstract
Background
Many older adults in the U.S. do not achieve the recommended amount of physical activity (PA) to fully realize a myriad of health benefits. Adiposity is one of those important correlates of PA and sedentary behaviors. However, the full extent to which adiposity is associated with PA and stationary time (STA) is uncertain. Therefore, we examined the association of adiposity with objectively measured PA and STA in black and white older adults.

Methods
We conducted a cross-sectional study of older adults enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003–2007 who participated in an ancillary accelerometer study 2009–2013. Assessment of body mass index (BMI) and waist circumference (WC) was completed during an in-home visit in the parent study. PA was measured by Actical™ accelerometers, which provided estimates of moderate-to-vigorous-intensity PA (MVPA), light-intensity PA (LPA), and STA for 4–7 consecutive days. Data from accelerometers were standardized to square root percentages of total wear time per day (SqrtMVPA%, SqrtLPA%, and SqrtSTA%). Interactions were tested for BMI and WC by race and sex, separately.

Results
Data were available for 7873 participants (69.8 ± 8.7 yr, 54.2% women, 31.5% African American). In mixed linear regression models, significant interactions existed in BMI by race and sex for the SqrtMVPA%, WC by race and sex for the SqrtMVPA% and the SqrtLPA% model(p < 0.05). No interaction was significant for the logistic model of meeting the PA guideline or not. In subgroup analyses, BMI was inversely associated with SqrtMVPA%, SqrtLPA%, and positively related to SqrtSTA% in black women, white men and white women after adjustments. Similar patterns were observed between WC and SqrtMVPA%, SqrtLPA%, and SqrtSTA% in all groups, respectively. However, BMI was not associated with SqrtMVPA% in black men. Those with higher BMI or WC were less likely to meet the PA guideline in all groups.

Conclusions
Adiposity was inversely associated with higher levels of MVPA/LPA and positively associated with higher levels of STA among black and white older adults. Prevention efforts aimed at promoting weight control may be beneficial to prevent physical inactivity and sedentary lifestyle among older adults.
Renal expression of cytokines and chemokines in diabetic nephropathy
Authors: Araújo Liliane Silvano , Torquato Bianca Gonçalves Silva , da Silva Crislaine Aparecida , dos Reis Monteiro Maria Luíza Gonçalves , dos Santos Martins Ana Luisa Monteiro , da Silva Marcos Vinícius , dos Reis Marlene Antônia , Machado Juliana Reis 
Published: July 2020

AbstractBackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function.MethodsForty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1β, and IL-6 were evaluated by immunohistochemistry.ResultsThe DN group showed a significant increase in IL-6 (p < 0.0001), IL-1β (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566).ConclusionsOur results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1β, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.
Barriers and associated factors for adequate antenatal care among Afghan women in Iran; findings from a community-based survey
Authors: Dadras Omid , Dadras Fateme , Taghizade Ziba , Seyedalinaghi Seyedahmad , Ono-Kihara Masako , Kihara Masahiro , Nakayama Takeo 
Published: July 2020

Abstract
Background
Almost a third of Afghan women living in Iran are at childbearing age. Antenatal care (ANC) is an inextricable part of healthy pregnancy and could prevent the adverse birth outcomes. Almost 97% of Iranian expectant women are receiving adequate ANC (4 or more visits). However, the situation for pregnant Afghan women is unclear. Some studies indicated low access to ANC among Afghan women. In the present study, we aimed to explore the sociodemographic factors and potential barriers associated with adequate ANC among Afghan women in Iran.

Methods
A cross sectional study was conducted between June 2019 and August 2019. Using time location sampling (TLS), we recruited 424 Afghan women aged 18–45 years old at three health centers in south region of Tehran. The data were collected on sociodemographic characteristics and the reported reasons for inadequate ANC using a questionnaire and analyzed applying bivariate, and multivariate analyses. Factor analysis was performed to reduce the number of potential reasons for inadequate ANC in order to improve the precision of regression analysis.

Results
Almost a third of Afghan women in this study had adequate ANC (≥ 8 visits). The women in older age group, those with higher education and family income, women with longer length of stay, those of legal status were more likely to have adequate ANC. In multivariate analysis, the poor knowledge and attitude toward ANC (AOR = 0.06; 95% CI [0.03–0.15]), the poor quality of services (AOR = 0.17 95% CI [0.07–0.41]); and to some extent, the difficulties in access (AOR = 0.33; 95% CI [0.11–1.00]) were the main obstacles toward adequate ANC among the study population.

Conclusion
Our study emphasized the important role of the personal knowledge and attitude toward ANC with adequate antenatal care among Afghan women in Iran. This could be addressed by well-oriented interventions and health education for Afghan women. The collaboration between central government with international agencies should be directed toward enhancing the social support, promoting the awareness and knowledge, and expanding the safety net services to improve the access and quality care among Afghan women in Iran.
Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma
Authors: Tian Zhichao , Zhang Fan , Li Po , Wang Jiaqiang , Yang Jinpo , Zhang Peng , Yao Weitao , Wang Xin 
Published: July 2020

AbstractBackgroundThe evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the evidence and clinical data of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare.MethodsThe clinical data of metastatic STS patients who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively analysed. All these patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the effectiveness and safety of nab-paclitaxel and gemcitabine in these patients.ResultsA total of 17 patients treated with nab-paclitaxel/ gemcitabine were enrolled in this study. One patient with angiosarcoma achieved complete response, 6 patients had partial response, 5 patients achieved stable disease, and 5 patients had progressive disease. The average diameter change in target lesion from baseline was − 19.06 ± 45.74%. And median progression free survival was 6 months (95% CI, 2–9 months). Grade 3 / 4 adverse events were not common, included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred.ConclusionNab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.