bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide (NA) Treatment Improves Response to G-CSF in Severe Congenital Neutropenia (SCN) Patients
Authors: Deordieva Ekaterina , Skokowa Julia , Shcherbina Anna , Novichkova Galina , Maschan Alexey , Welte Karl 
Published: November 2020

Background: SCN is an inherited bone marrow failure syndrome with markedly reduced granulocyte numbers and functions that often manifests with life-threatening bacterial infections. G-CSF treatment is the primary therapeutic approach, yet some SCN patients require high doses of G-CSF which increases the risk of acute myeloid leukemia development, or do not respond to GCSF at al. We have demonstrated that nicotinamide (NA) treatment increases granulocyte numbers in healthy volunteers.
Aim: To asses the effect of NA treatment in SCN and cyclic neutropenia (CyN) patients.
Methods: 15 SCN and three CyN patients ages 0.5 to 31 (M-5.47) years were orally treated with 20 mg/kg/day of NA in addition to G-CSF therapy. G-CSF dose varied between 0.6 and 50.8 µg/kg/day before start of NA treatment.
Results: After three months of NA treatment, absolute neutrophil counts (ANC) increased from median 0.80 x 109/l (Q1 0.61, Q3 1.29 x 109/l) to 1.77 x 109/l (Q1 1.49, Q3 2.33 x 109/l) (p &lt; 0.001). This allowed G-CSF dose reduction from 15 µg/kg/day (Q1 5, Q3 25 µg/kg/day) to 10 µg/kg/day (Q1 1.77, Q3 15.16 µg/kg/day) in 17 patients, and complete G-CSF tapering in one patient. After one year of observations, ANC were 1.50 x 109/l (Q1 0.99, Q3 2.86 x 109/l), median increase of ANC from start of therapy was 0.89 x 109/l fold (Q1 0.39, Q3 1.57; р = 0.004). NA was well tolerated, without severe adverse events. We also observed a marked reduction of the frequency and severity of bacterial infections upon combination of NA and G-CSF.
Conclusions: In our group of SCN/CyN patients, NA treatment led to increased neutrophil counts and decreased required G-CSF doses with continuous clinical and laboratory responses. We also observed a reduction of the frequency and severity of bacterial infections. Therefore, the use of NA in combination with a reduced dose of G-CSF for the treatment of SCN and CyN patients is promising and should be further investigated in a larger cohort of patients.

Disclosures
No relevant conflicts of interest to declare.
Differential Use of Rap1 Effectors for Integrin Activation in Platelets and Lymphocytes
Authors: Lagarrigue Frederic , Sun Hao , Gingras Alexandre R , Ginsberg Mark H 
Published: November 2020

Rap1 is a major convergence point of the platelet and lymphocyte signaling pathways that result in talin1 binding to the integrin β-cytoplasmic domain and consequent integrin activation, effective hemostasis and immune functions. The nature of the connection between Rap1 and talin1 in integrin activation is an important remaining gap in our understanding of this process. Deletion of RIAM in T cells partially suppressed αLβ2 and α4β7 integrin activation but did not block activation of α4β1. In sharp contrast, deletion of both Rap1a and Rap1b isoforms or deletion of talin1 profoundly suppressed activation of α4β1 in addition to the other two integrins. The loss of homing of T cells to peripheral lymphoid organs was correlated with the loss of integrin activation in these mutant T cells. We recently identified two Rap1 binding sites in talin1 F0 and F1 domains and generated mice bearing point mutations, which block Rap1 binding to both talin1 F0 and F1 domains (R35E,R118E). In platelets, which lack endogenous RIAM, a talin1 (R35E,R118E) mutation suppresses activation of integrin αIIbβ3 and platelet aggregation to a similar extent to that observed in Rap1a,b null platelets. In contrast, talin1 (R35E,R118E)-expressing T cells manifest only partial loss of integrin activation, whereas RIAM null T cells expressing talin1 (R35E,R118E) exhibit a much more profound defect. Importantly, overexpression of RIAM can completely rescue the integrin activation defect in talin1 (R35E,R118E)-expressing T cells indicating that Rap1 binding to RIAM and talin1 are partially redundant in T cells. These findings reveal that although both Rap1 and talin1 are essential for integrin action in blood cells, the connections between them vary in different blood cells and that the final steps in integrin activation and blood cell function can be manipulated in a cell-type specific manner.

Disclosures
No relevant conflicts of interest to declare.
Venous Thromboembolic Disease in Children Associated with COVID-19
Authors: Narang Shalu , Morparia Kavita , Sharma Prachi 
Published: November 2020

Venous thromboembolism (VTE) in children is rare and VTE in association with antiphospholipid antibodies (lupus anticoagulant, cardiolipin antibodies and beta-2 glycoprotein I) is even rarer. The development of these antibodies can be due to an acute infection or an autoimmune disease. Recently, these antibodies have been noted to be present in conjunction with SARS-CoV-2 in adult patients with VTE.
We report 5 cases of VTE associated with presence of antiphospholipid antibodies in children over a short period during the coronavirus 19 pandemic. One child had SARS-CoV-2 PCR positive on nasopharyngeal swab while 2 had positive antibodies (IgM) to SARS-CoV-2. One adolescent female had features of Multi-Inflammatory System in Children (MIS-C) a few weeks before presenting with multiple pulmonary emboli and DVT. Thrombotic events included DVT of lower extremity (3 patients), multiple PE (2 patients), orbital vein thrombosis (1 patient) and upper extremity DVT (1 patient). Two of these patients had both DVT and PE. All patients had one or more antiphospholipid antibody present. Two adolescent females had new onset of systemic lupus erythematous. All patients were treated with systemic anticoagulation with heparin (initially with unfractionated heparin if clinically unstable and later changed to low molecular weight heparin).
We report a cluster of adolescents with unusual thrombotic complications with antiphospholipid antibody positivity during the coronavirus 19 pandemic, 3 with positive virologic criteria, one with delayed presentation after MIS-C like features and one with close family member exposure. We hypothesize that VTE in children is likely due to development of antiphospholipid antibodies when associated with SARS-CoV-2 infection.

Disclosures
No relevant conflicts of interest to declare.
The Samd14-Capping Protein Complex Controls Cell Signaling in the Erythropoietic Stress Response
Authors: Hewitt Kyle J 
Published: November 2020

In anemia, restoring homeostatic levels of erythrocytes requires an erythropoietic regenerative response to accelerate red blood cell (RBC) production. Elucidating mechanisms that drive the process of erythropoiesis in the context of regeneration or "stress erythropoiesis" can reveal new strategies for targeting ineffective erythropoiesis. An important component of stress erythropoiesis involves stress-dependent activation of genes/proteins through transcriptional enhancers. We discovered an enhancer in intron 1 of the Sterile Alpha Motif (SAM) Domain 14 (Samd14) gene elevates Samd14 expression, facilitates SCF/c-Kit signaling, and is needed for survival in a hemolytic anemia model. However, it is dispensable for erythropoietic development. Our prior work demonstrated that the SAM domain of Samd14 promotes c-Kit-mediated cellular signaling to regulate progenitor function, and this SAM domain has functional attributes unique from those of structurally related SAM domains. Using immunoprecipitation-mass spectrometry, we determined that Samd14 interacts with the Capzβ protein. Capzβ is a component of the actin capping protein (CP) complex, which interact as α- and β heterodimers during actin filament assembly/disassembly. CP exerts diverse functions in cell motility, vesicular transport, cell signaling and cytokinesis. Using a series of Samd14 deletion constructs, we tested whether the Samd14-Capzβ interaction is important for Samd14 promotion of c-Kit signaling in stress erythroid progenitors. Our findings determined that the region of Samd14 required for binding to Capzβ (amino acids 38-54) were required to restore c-Kit signaling. Our ongoing studies are examining whether Samd14-Capzβ is similarly required for colony formation and cell survival of stress erythroid progenitors, and whether additional SAM domain-containing proteins have a similar role in regulating stress erythropoiesis. Understanding the fundamental drivers of regenerative erythropoiesis can lead to new therapeutic strategies and prognostic/diagnostic markers.

Disclosures
No relevant conflicts of interest to declare.
Improvement in Survival for Elderly Pts with AML over the Years: A NCDB Analysis
Authors: Master Samip R , Mansour Richard Preston , Shi Runhua 
Published: November 2020

Objective: There has been significant changes in management of acute myeloid leukemia (AML) over past few years with bunch of new medications approved for AML management. We did a retrospective study to investigate if the recent improvement in AML management options have led to improved survival in elderly AML pts.
Subjects and Methods: Patients with AML from 2004-2014 between age from 60-90 years were included in the retrospective study. Chi-square analysis was used to assess the association between treatment and factors investigated. Kaplan-Meier method was used to assess overall survival. Log rank methods were used to determine factors significant for survival. Multivariable Cox regression analysis was used to determine the independent variables.
Results: 37,617 patients from the National Cancer Database were eligible for this study. Twenty-seven, thirty-six and thirty-seven percentage of pts were in the age group more than/equal to eighty, between 70-79 years and 60-69 years, respectively. The median survival in months of pts between 60-69 years, 70-79 years and &gt;= 80 years was 9.5, 3.8 and 1.4 respectively. The median survival of pts did improve the years with median survival of 3.3 m, 3.7 m and 5 m in pts who got diagnosed between 2004-2007, 2008-2010 and 2011-2014 respectively. On multivariate analysis, after adjusting for all variable including age, gender, race, treatment received and comorbidity index, the year of AML diagnosis was statistically significant predictor of overall survival. The pts who got diagnosed between 2011-2014 were 19 % less likely to die compared to those diagnosed between 2004-2007.
Conclusion: Survival analysis on AML in the National Cancer Database showed that survival in elderly pts with AML has improved over the years with pts who were diagnosed between 2011-2014 were 19 % less likely to die compared to pts diagnosed between 2004-2007.

Disclosures
No relevant conflicts of interest to declare.
Loss function of SL (sekiguchi lesion) in the rice cultivar Minghui 86 leads to enhanced resistance to (hemi)biotrophic pathogens
Authors: Tian Dagang , Yang Fang , Niu Yuqing , Lin Yan , Chen Zaijie , Li Gang , Luo Qiong , Wang Feng , Wang Mo 
Published: November 2020

Abstract

Background
Serotonin, originally identified as a neurotransmitter in mammals, functions as an antioxidant to scavenge cellular ROS in plants. In rice, the conversion of tryptamine to serotonin is catalyzed by SL (sekiguchi lesion), a member of cytochrome P450 monooxygenase family. The sl mutant, originated from rice cultivar Sekiguchi-asahi, exhibits spontaneous lesions, whereas its immune responses to pathogens have not been clearly characterized.

Results
Here we identified three allelic mutants of SL in an indica rice restore line Minghui 86 (MH86), named as sl-MH-1, − 2 and − 3, all of which present the typical lesions under normal growth condition. Compared with those in MH86, the serotonin content in sl-MH-1 is dramatically decreased, whereas the levels of tryptamine and L-trytophan are significantly increased. The sl-MH-1 mutant accumulates high H2O2 level at its lesion sites and is more sensitive to exogenous H2O2 treatment than the wild type. When treated with the reductant vitamin C (Vc), the lesion formation on sl-MH-1 leaves could be efficiently suppressed. In addition, sl-MH-1 displayed more resistant to both the blast fungus and blight bacteria, Pyricularia oryzae (P. oryzae, teleomorph: Magnaporthe oryzae) and Xanthomonas oryzae pv. Oryzae (Xoo), respectively. The pathogen-associated molecular patterns (PAMPs)-triggered immunity (PTI) responses, like reactive oxygen species (ROS) burst and callose deposition, were enhanced in sl-MH-1. Moreover, loss function of SL resulted in higher resting levels of the defense hormones, salicylic acid and jasmonic acid. The RNA-seq analysis indicated that after P. oryzae infection, transcription of the genes involved in reduction-oxidation regulation was the most markedly changed in sl-MH-1, compared with MH86.

Conclusions
Our results indicate that SL, involving in the final step of serotonin biosynthesis, negatively regulates rice resistance against (hemi)biotrophic pathogens via compromising the PTI responses and defense hormones accumulation.
Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis
Authors: Xu Xiao-Hong , Sun Bo , Zhong Shan , Wei Dong-Dong , Hong Ze , Dong Ai-Qiang 
Published: November 2020

Abstract

Background
The prognostic significance of diabetic retinopathy (DR) for cardiovascular diseases (CVD) remained unclear. Therefore, we performed this meta-analysis to assess whether DR predicted CVD mortality in diabetic patients.

Methods
We searched PubMed, Embase, Web of Science and Cochrane Library for cohort studies reporting the association of DR and CVD mortality. Then we pooled the data for analysis.

Results
After screening the literature, 10 eligible studies with 11,239 diabetic subjects were finally included in quantitative synthesis. The pooled risk ratio (RR) of DR, mild DR, and severe DR for CVD mortality was 1.83 (95% confidence interval (CI): 1.42, 2.36; p < 0.001), 1.13 (95% CI 0.81, 1.59; p = 0.46), and 2.26 (1.31, 3.91; p = 0.003), respectively, compared to those without DR. In type 2 DM, the patients with DR had a significantly higher CVD mortality (RR: 1.69; 95% CI 1.27, 2.24; p < 0.001). Subgroup analysis also showed a significantly higher CVD mortality in DR according to various regions, study design, data source, and follow-up period (all RR > 1; all P values < 0.05). Data from 2 studies showed no significant correlation of DR and CVD mortality in diabetic patients receiving cardiovascular surgery (RR: 2.40; 95% CI 0.63, 9.18; P = 0.200).

Conclusions
DR is a risk marker of cardiovascular death, and severe DR predicts a doubled mortality of CVD in diabetes. These findings indicate the importance of early identification and management of diabetic patients with DR to reduce the risk of death.
“A false sense of confidence” The perceived role of inflammatory point-of-care testing in managing urinary tract infections in Dutch nursing homes: a qualitative study
Authors: Kuil S. D. , Schneeberger C. , van Leth F. , de Jong M. D. , Harting J. 
Published: November 2020

Abstract

Background
Diagnosing urinary tract infections (UTI) in nursing home residents is complex, due to frequent non-specific symptomatology and asymptomatic bacteriuria. The objective of this study was to explore health care professionals’ perceptions of the proposed use of inflammatory marker Point-Of-Care Testing (POCT) in this respect.

Methods
We conducted a qualitative inquiry (2018–2019) alongside the multicenter PROGRESS study (NL6293), which assessed the sensitivity of C-reactive protein and procalcitonin POCT in UTI. We used semi-structured face-to-face interviews. The participants were physicians (n = 12) and nurses (n = 6) from 13 nursing homes in the Netherlands. Most respondents were not familiar with inflammatory marker POCT, while some used POCT for respiratory tract infections. Both the interview guide and the analysis of the interview transcripts were based on the Consolidated Framework for Implementation Research.

Results
All respondents acknowledged that sufficiently sensitive POCT could decrease diagnostic uncertainty to some extent in residents presenting with non-specific symptoms. They primarily thought that negative test results would rule out UTI and justify withholding antibiotic treatment. Secondly, they described how positive test results could rule in UTI and justify antimicrobial treatment. However, most respondents also expected new diagnostic uncertainties to arise. Firstly, in case of negative test results, they were not sure how to deal with residents’ persisting non-specific symptoms. Secondly, in case of positive test results, they feared overlooking infections other than UTI. These new uncertainties could lead to inappropriate antibiotics use. Therefore, POCT was thought to create a false sense of confidence.

Conclusions
Our study suggests that inflammatory marker POCT will only improve UTI management in nursing homes to some extent. To realize the expected added value, any implementation of POCT requires thorough guidance to ensure appropriate use. Developing UTI markers with high negative and positive predictive values may offer greater potential to improve UTI management in nursing homes.
Associated factors of secondary sex ratio of offspring in assisted reproductive technology: a cross-sectional study in Jilin Province, China
Authors: Wang Mohan , Liu Xiangyin , Zhang Han , Li Leilei , Liu Ruizhi , Zhang Hongguo , Yu Yang 
Published: November 2020

Abstract

Background
The aim of this study was to determine the secondary sex ratio (SSR) of offspring in assisted reproduction technology (ART) in Jilin Province, China, and to analyse the influencing factors associated with SSR.

Methods
A cross-sectional study of 3833 babies including singletons and twins born to 2990 couples treated by ART between May 2011 and December 2018 was performed.

Results
The main outcomes of this study were that the SSR of ART babies in Jilin Province was 50.64% and the SSR was associated with fertilization methods (p < 0.05). Comparing to in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) (OR = 0.808, 95%CI: 0.681–0.958) decreased the percentage of male babies.

Conclusions
This study suggests that the SSR of ART births in Jilin Province was lower than the normal level and ICSI had a significant effect on SSR. Though we need more samples to study in the future, we still need to think about the impact of ICSI on SSR in ART.
Striving for a more person-centered psychosis care: results of a hospital-based multi-professional educational intervention
Authors: Allerby Katarina , Goulding Anneli , Ali Lilas , Waern Margda 
Published: November 2020

AbstractBackgroundReluctance on the part of mental health professionals constitutes an important barrier to patient participation in care. In order to stimulate person-centeredness in the inpatient care of persons with psychotic illness, we developed and tested an educational intervention for hospital staff (including psychiatrists) at all four wards at the Psychosis Clinic, Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention was co-created by professionals, patients, and researchers using a participatory approach. In addition to lectures and workshops, staff created and implemented small projects to increase person-centeredness on their own wards. A primary focus was to establish a partnership between patient and staff by capturing and utilizing the patient’s narrative to support active engagement in the care process. This included the development of a person-centered care plan. We hypothesized that the intervention would be associated with increased patient empowerment (primary outcome) and satisfaction with care (secondary outcome).MethodsA before and after design was used to test group differences in patient empowerment (Empowerment Scale) and consumer satisfaction (UKU-ConSat Rating Scale). All patients receiving inpatient psychosis care during measuring periods were eligible if meeting inclusion criteria of schizophrenia spectrum disorder, age > 18, and ability to comprehend study information. Severe cognitive deficit and inadequate Swedish language skills were exclusion criteria. Data on possible confounding variables including overall health (EQ-5D), symptom burden (PANSS), and functional ability (GAF) were collected alongside outcome measures.ResultsANCOVAs with overall health as a confounding variable showed no group differences regarding empowerment before (n = 50) versus after (n = 49) intervention, sample mean = 2.87/2.99,p = .142,eta2 = .02, CI = -.27–.04. Consumer satisfaction (n = 50/50) was higher in the post-implementation group (4.46 versus 11.71,p = .041eta2 = .04, CI = -14.17– -.31).ConclusionThe hypothesis regarding the primary outcome, empowerment, was not supported. An increase in the secondary outcome, satisfaction, was observed, although the effect size was small, and results should be interpreted with caution. Findings from this staff educational intervention can inform the development of future studies aimed at improvement of inpatient care for persons with severe mental illness.Trial registrationThe trial was retrospectively registered atClinicalTrials.govJune 9, 2017, identifier:NCT03182283
Reactive attachment disorder symptoms and prosocial behavior in middle childhood: the role of Secure Base Script knowledge
Authors: Cuyvers Bien , Vervoort Eleonora , Bosmans Guy 
Published: November 2020

AbstractBackgroundChildren with attachment disorder show prosocial behavior problems. Children with a reactive attachment disorder show inhibited and emotionally withdrawn behavior. Consequently, these children typically display prosocial behavior problems. However, the underlying mechanism between reactive attachment disorder and prosocial behavior problems is still unclear and findings in literature are mixed.MethodsThe current study investigated the role of children’s attachment representations in this association. Attachment representations reflect knowledge about a cognitive script regarding the attachment figure as a source for support (Secure Base Script). We tested whether secure base script knowledge 1) mediates or 2) moderates the link between reactive attachment disorder and prosocial behavior problems in 83 children (6–11 years; 83.1% boys) recruited from special education schools for children with behavioral problems. Children completed a pictorial Secure Base Script Test. Their reactive attachment disorder symptoms were assessed during an interview with the primary caregivers. Primary caregivers and teachers filled out a prosocial behavior questionnaire about the child.ResultsResults did not support the mediation hypothesis, but evidence for the moderation hypothesis was found. Secure base script knowledge attenuated the negative association between attachment disorder symptoms and prosocial behavior.ConclusionsThese findings contribute to the discussion about the link between attachment representations and attachment disorders.