bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Role of Hemostasis Variables in Cardiometabolic Outcomes
Authors: Lopez Alberto D. , Patel Kanisha , Diego Vincent P. , Almeida Marcio A. , Blangero John , Powell Jerry S. , Howard Tom E. 
Published: November 2021

Abstract
Background: Hemostasis variables represent well-known pathogenic determinants of venous-thromboembolism and are hypothesized to influence risk for cardiometabolic outcomes (CMOs) by effecting susceptibility to vascular inflammation and/or endothelial dysfunction.
Methods: We investigated in Mexican American (MA)-participants of the San Antonio Family Study the effects of 20 measured hemostasis variables on CMOs including type-2 diabetes (T2D), impaired-fasting glucose (IFG), insulin resistance (IR), hypertension, obesity based on sex-specific waist circumference (OBWC), low high-density lipoprotein (Low-HDL)-cholesterol, hypertriglyceridemia, and a heart distress (HD) variable comprised of history of heart attack and/or heart surgery. The hemostasis variables included PT, aPTT, TFPI, aPC-ratio, fibrinogen, von Willebrand Factor (VWF), ADAMST-13, D-dimer, fPS, tPS, plasminogen, and factor (F)II, FV, FVII, FVIII, FX, FXI, and FXII of the coagulation system. We used a backward stepwise-regression selection approach to identify the preliminary sets of hemostasis predictors.
Results: Our final regression models consisted of the final set of hemostasis variables while accounting for age and sex as covariates. For the T2D, IFG, and HD outcomes, VWF was the only significant hemostasis predictor (p&lt;0.05). In each case, VWF was positively associated with the outcome. The hemostasis variable fibrinogen was a significant positive predictor for the IR, OBWC, and Low-HDL-cholesterol outcomes (p&lt;0.05). For OBWC, FV was an additional significant positive predictor (p&lt;0.05). Finally, no hemostasis variables significantly predicted hypertension or hypertriglyceridemia.
Conclusions: Our results demonstrate that, among the MA-population, all measured CMOs-except hypertension and hypertriglyceridemia-are significantly influenced by individual-variability in several hemostasis parameters with most important predictors being VWF and fibrinogen.
Keywords: Hemostasis; Venous-thromboembolism; Cardiovascular diseases/disorders; Metabolic syndrome; Inflammation; Endothelial dysfunction; Mexican American; Coagulation factors; von Willebrand Factor; and Fibrinogen

Disclosures
No relevant conflicts of interest to declare.
Reduced-Dose Venetoclax Is Well Tolerated and Cost Effective for the Treatment of Chronic Lymphocytic Leukemia in Frail Older Adults
Authors: Marin Monica Pernia , Alharbi Malak , Chhina Arashpreet , Thomas Shrina P , Jain Maneesh 
Published: November 2021

Abstract
Venetoclax is a potent selective inhibitor of the anti-apoptotic protein B-Cell Lymphoma 2 (BCL2) on tumor cells restoring the process of apoptosis among cancer cells. Venetoclax has been approved by the US Food and Drug administration (FDA) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion (del[17p]) who received at least one prior therapy. CLL is the most common leukemia in older adults and its treatment is often challenging given the multiple comorbidities, impaired mobility, and poor functional reserved affecting this patients' population. Emerging targeted therapy for relapsing CLL such as Venetoclax has provided hope, however, there is limited data regarding its efficacy and safety in the geriatric population. Although, a recent international cohort study showed that Venetoclax had similar efficacy in the elderly, those older than 75 years had a higher rate of treatment discontinuation due to toxicity which can lead to significant complications, multiple hospitalizations, and increased healthcare costs. For veterans, the annual treatment cost using the manufacturer-recommended dose of Venetoclax is close to $100,000. As it is common to reach complete remission with Venetoclax monotherapy, patients most likely will remain on therapy long-term, compounding financial impact over their treatment lifetime. Reduced dose Venetoclax can lower total cost by 50% or more thereby decreasing the economic burden, which would ultimately improve treatment adherence. In addition, Venetoclax dose reductions could potentially allow disease control while decreasing the rate and intensity of side effects and adverse events in frail older adults. Therefore, we present our experience using a reduced Venetoclax dose, which led to complete remission in the treatment of two frail older adults with relapsing CLL at the Washington DC Veterans Affairs Medical Center. We report the disease control as evidenced by decrease in white blood cell count and alleviation of "B symptoms" along with side effects with a Venetoclax dose ranging from 100-200 mg per day. We also report the cost benefits obtained with the use of a reduced Venetoclax dose. We hope that sharing our experience encourages clinical trials aiming to determine the minimal dose of Venetoclax needed to effectively treat CLL while limiting toxicity, decreasing health care costs, and preserving quality of life in frail older adults.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Induced cell-autonomous neutropenia systemically perturbs hematopoiesis in Cebpa enhancer-null mice
Authors: Avellino Roberto , Mulet-Lazaro Roger , Havermans Marije , Hoogenboezem Remco , Smeenk Leonie , Salomonis Nathan , Schneider Rebekka K. , Rombouts Elwin , Bindels Eric , Grimes Lee , Delwel Ruud 
Published: November 2021

Abstract
The transcription factor C/EBPa initiates the neutrophil gene expression program in the bone marrow (BM). Knockouts of the Cebpa gene or its +37kb enhancer in mice show 2 major findings: (1) neutropenia in BM and blood; (2) decrease in long-term hematopoietic stem cell (LT-HSC) numbers. Whether the latter finding is cell-autonomous (intrinsic) to the LT-HSCs or an extrinsic event exerted on the stem cell compartment remained an open question. Flow cytometric analysis of the Cebpa +37kb enhancer knockout model revealed that the reduction in LT-HSC numbers observed was proportional to the degree of neutropenia. Single-cell transcriptomics of wild-type (WT) mouse BM showed that Cebpa is predominantly expressed in early myeloid-biased progenitors but not in LT-HSCs. These observations suggest that the negative effect on LT-HSCs is an extrinsic event caused by neutropenia. We transplanted whole BMs from +37kb enhancer-deleted mice and found that 40% of the recipient mice acquired full-blown neutropenia with severe dysplasia and a significant reduction in the total LT-HSC population. The other 60% showed initial signs of myeloid differentiation defects and dysplasia when they were sacrificed, suggesting they were in an early stage of the same pathological process. This phenotype was not seen in mice transplanted with WT BM. Altogether, these results indicate that Cebpa enhancer deletion causes cell-autonomous neutropenia, which reprograms and disturbs the quiescence of HSCs, leading to a systemic impairment of the hematopoietic process.
Molecular evolution of chloroplast genomes in subfamily Zingiberoideae (Zingiberaceae)
Authors: Li Dong-Mei , Li Jie , Wang Dai-Rong , Xu Ye-Chun , Zhu Gen-Fa 
Published: November 2021

Abstract
Background
Zingiberoideae is a large and diverse subfamily of the family Zingiberaceae. Four genera in subfamily Zingiberoideae each possess 50 or more species, including Globba (100), Hedychium (> 80), Kaempferia (50) and Zingiber (150). Despite the agricultural, medicinal and horticultural importance of these species, genomic resources and suitable molecular markers for them are currently sparse.

Results
Here, we have sequenced, assembled and analyzed ten complete chloroplast genomes from nine species of subfamily Zingiberoideae: Globba lancangensis, Globba marantina, Globba multiflora, Globba schomburgkii, Globba schomburgkii var. angustata, Hedychium coccineum, Hedychium neocarneum, Kaempferia rotunda ‘Red Leaf’, Kaempferia rotunda ‘Silver Diamonds’ and Zingiber recurvatum. These ten chloroplast genomes (size range 162,630–163,968 bp) possess typical quadripartite structures that consist of a large single copy (LSC, 87,172–88,632 bp), a small single copy (SSC, 15,393–15,917 bp) and a pair of inverted repeats (IRs, 29,673–29,833 bp). The genomes contain 111–113 different genes, including 79 protein coding genes, 28–30 tRNAs and 4 rRNA genes. The dynamics of the genome structures, gene contents, amino acid frequencies, codon usage patterns, RNA editing sites, simple sequence repeats and long repeats exhibit similarities, with slight differences observed among the ten genomes. Further comparative analysis of seventeen related Zingiberoideae species, 12 divergent hotspots are identified. Positive selection is observed in 14 protein coding genes, including accD, ccsA, ndhA, ndhB, psbJ, rbcL, rpl20, rpoC1, rpoC2, rps12, rps18, ycf1, ycf2 and ycf4. Phylogenetic analyses, based on the complete chloroplast-derived single-nucleotide polymorphism data, strongly support that Globba, Hedychium, and Curcuma I + “the Kaempferia clade” consisting of Curcuma II, Kaempferia and Zingiber, form a nested evolutionary relationship in subfamily Zingiberoideae.

Conclusions
Our study provides detailed information on ten complete Zingiberoideae chloroplast genomes, representing a valuable resource for future studies that seek to understand the molecular evolutionary dynamics in family Zingiberaceae. The identified divergent hotspots can be used for development of molecular markers for phylogenetic inference and species identification among closely related species within four genera of Globba, Hedychium, Kaempferia and Zingiber in subfamily Zingiberoideae.
A time-series prediction model of acute myocardial infarction in northern of Iran: the risk of climate change and religious mourning
Authors: Sharif Nia Hamid , Gorgulu Ozkan , Naghavi Navaz , Froelicher Erika Sivarajan , Fomani Fatemeh Khoshnavay , Goudarzian Amir Hossein , Sharif Saeed Pahlevan , Pourkia Roghiyeh , Haghdoost Ali Akbar 
Published: November 2021

Abstract
Background
Although various studies have been conducted on the effects of seasonal climate changes or emotional variables on the risk of AMI, many of them have limitations to determine the predictable model. The currents study is conducted to assess the effects of meteorological and emotional variables on the incidence and epidemiological occurrence of acute myocardial infarction (AMI) in Sari (capital of Mazandaran, Iran) during 2011–2018.

Methods
In this study, a time series analysis was used to determine the variation of variables over time. All series were seasonally adjusted and Poisson regression analysis was performed. In the analysis of meteorological data and emotional distress due to religious mourning events, the best results were obtained by autoregressive moving average (ARMA) (5,5) model.

Results
It was determined that average temperature, sunshine, and rain variables had a significant effect on death. A total of 2375 AMI’s were enrolled. Average temperate (°C) and sunshine hours a day (h/day) had a statistically significant relationship with the number of AMI’s (β = 0.011, P = 0.014). For every extra degree of temperature increase, the risk of AMI rose [OR = 1.011 (95%CI 1.00, 1.02)]. For every extra hour of sunshine, a day a statistically significant increase [OR = 1.02 (95% CI 1.01, 1.04)] in AMI risk occurred (β = 0.025, P = 0.001). Religious mourning events increase the risk of AMI 1.05 times more. The other independent variables have no significant effects on AMI’s (P > 0.05).

Conclusion
Results demonstrate that sunshine hours and the average temperature had a significant effect on the risk of AMI. Moreover, emotional distress due to religious morning events increases AMI. More specific research on this topic is recommended.
Patient preferences of healthcare delivery in irritable bowel syndrome: a focus group study
Authors: Masclee Gwen M. C. , Snijkers Johanna T. W. , Boersma Marijke , Masclee Ad A. M. , Keszthelyi Daniel 
Published: November 2021

Abstract
Background
Irritable bowel syndrome (IBS) is a highly prevalent disorder with significant negative impact on quality of life of patients that results in high healthcare use and costs. Improving healthcare outcomes for IBS patients is warranted,
however the exact needs of IBS patients with regard to therapy and control of symptoms are unknown.

Methods
Focus group interviews, using a two-stage model, were performed with twenty-three IBS patients meeting Rome III criteria and one mother of a patient, from four different regions from the Netherlands.

Results
Twenty-four participants were included of whom majority were female (n = 21), mean age was 43 years, and mean duration of IBS was 18 years. Five categories of patients’ perspectives were identified: clear communication, a multidisciplinary treatment team, centers of expertise, focus on scientific research and information about IBS that is widely available for patients.

Conclusions
Based on these findings we highlight the need for IBS care givers to take these key items into account in IBS care. These elements aid clinicians, but mostly patients, in coping and management of symptoms and subsequent healthcare outcomes, reducing overall healthcare use and costs.
Comparison of real-time PCR and nested PCR for toxoplasmosis diagnosis in toxoplasmic retinochoroiditis patients
Authors: Khanaliha Khadijeh , Bokharaei-Salim Farah , Hedayatfar Alireza , Esteghamati Abdoulreza , Alemzadeh Sayyed Amirpooya , Asgari Qasem , Garshasbi Saba , Salemi Borna 
Published: November 2021

Abstract
Backgrounds
PCR is a proper technique that significantly improves toxoplasmosis diagnosis. However, a more sensitive technique is required. This study compared real-time PCR with nested PCR using B1, SAG-4, and MAG-1 bradyzoite genes to diagnose toxoplasmosis in toxoplasmic retinochoroiditis patients.

Methods
Blood samples were collected from 10 patients with active toxoplasmic chorioretinal lesions and 10 healthy individuals. Blood samples including peripheral blood mononuclear cells (PBMCs), serum and whole blood samples were used for DNA extraction. Serum was also used to detect anti-toxoplasma IgG and IgM antibodies. Nested PCR and real-time PCR were performed using B1, SAG-4, and MAG-1 target genes.

Results
Five (50%) out of the 10 patients were tested positive for toxoplasmosis with nested PCR using the PBMC samples. All the five patients tested positive with nested PCR were also tested positive for toxoplasmosis with real-time PCR using the PBMC samples. The real-time PCR results demonstrated that 9(90%) out of the 10 patients were positive based on B1 and the remaining one (10%) was positive only based on MAG-1. In general, of the patients, five (50%) were positive using SAG-4 and three (30%) were positive in term of MAG-1 using PBMCs with real-time PCR.

Conclusion
It appears that PBMC samples have the best performance as the PCR extraction method and are a good source for toxoplasmosis diagnosis. The use of B22 and B23 target genes due to their high sensitivity and specificity along with bradyzoite genes are recommended for toxoplasmosis diagnosis using PBMC samples with real-time PCR.
Clinical utility of quantitative analysis of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis
Authors: Lee Jeong Won , Chang Sung Hae , Jang Su Jin , Park Hee Jin , Lee Sang Mi , Jung Ki Jin 
Published: November 2021

Abstract
Background
The purpose of this study was to investigate the efficiency of quantitative parameters of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.

Methods
We retrospectively enrolled 65 patients with rheumatoid arthritis who underwent bone scintigraphy for diagnostic work-up. Quantitative analysis of bone scintigraphy images was conducted using an in-house software, and joint uptake ratio of 28 joints was measured for the calculation of the disease activity score of 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between joint uptake ratio and clinical findings and the efficiency of joint uptake ratio in detecting clinically active joint and high disease activity were assessed.

Results
Clinically active joint (tender and/or swollen joints) showed significantly higher joint uptake ratio than did other non-affected joints (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of joint uptake ratio for identifying clinically active joint were 78.7%, 52.0%, 32.9%, and 89.1%, respectively, and those of the summed joint uptake ratio for detecting high disease activity were 92.9%, 66.8%, 43.3%, and 97.1%, respectively; the joint uptake ratio showed high detection ability, especially for active joints of the elbow, wrist, and metacarpo-phalangeal joint areas. The summed joint uptake ratio of 28 joints showed a significantly strong positive correlation with DAS28-ESR (p < 0.001; correlation coefficient, 0.725).

Conclusion
Quantitative parameters of bone scintigraphy showed high sensitivity and NPV for detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.
Expectations of treatment outcomes in patients with spinal metastases; what do we tell our patients? A qualitative study
Authors: Versteeg Anne L. , Gal Roxanne , Charest-Morin Raphaele , Verlaan Jorrit-Jan , Wessels Hester , Fisher Charles G. , Verkooijen Helena M. 
Published: November 2021

Abstract
Background
Realistic pre-treatment expectations are important and have been associated with post-treatment health related quality of life (HRQOL). Patient expectations are greatly influenced by physicians, as they are the primary resource for information. This study aimed to explore the communication practices of physicians regarding treatment outcomes for patients with spinal metastases, and physician experiences with patients’ pre-treatment expectations.

Methods
An international qualitative study using semi-structured interviews with physicians routinely involved in treating metastatic spine disease (spine surgeons, radiation and medical oncologists, and rehabilitation specialists) was conducted. Physicians were interviewed about the content and extent of information they provide to patients with spinal metastases regarding treatment options, risks and treatment outcomes. Interviews were transcribed verbatim and analyzed using a thematic coding network.

Results
After 22 interviews data saturation occurred. The majority of the physicians indicated that they currently do not establish patients’ pre-treatment expectations, despite acknowledging the importance of these expectations. Spine surgeons often believe that patient expectations are disproportionate. Physicians expressed they manage expectations by detailing the most common risks and providing a broad but nonspecific overview of treatment outcomes. While the palliative intent seems clear to the physicians, their perception is that the implications of a palliative treatment remains elusive to most patients.

Conclusion
This study highlights the current gap in patient-physician communication regarding expectations of treatment outcomes of patients with spinal metastases. These results warrant further research to improve communication practices and determine the effect of patient expectations on patient reported outcomes in this population.
Characteristics of in-hospital mortality of congenital heart disease (CHD) after surgical treatment in children from 2005 to 2017: a single-center experience
Authors: Zheng Guilang , Wu Jiaxing , Chen Peiling , Hu Yan , Zhang Huiqiong , Wang Jing , Zeng Hanshi , Li Xufeng , Sun Yueyu , Xu Gang , Wen Shusheng , Cen Jianzheng , Chen Jimei , Guo Yuxiong , Zhuang Jian 
Published: November 2021

Abstract
Background
To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children’s CHD after thoracotomy.

Methods
This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017.

Results
A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05).

Conclusions
The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.
How best to provide help to bereaved adolescents: a Delphi consensus study
Authors: Ross Anna M , Krysinska Karolina , Rickwood Debra , Pirkis Jane , Andriessen Karl 
Published: November 2021

Abstract
Background
Many adolescents struggle with their grief and mental health issues after the death of a close person, such as a family member or a friend. Given the potentially devastating impact of the loss on the adolescent and their family, professional help can be warranted. However, little is known about how to best help these adolescents. This study aimed to address this gap by determining what help professionals (i.e., counselors) should provide to bereaved adolescents.

Methods
The Delphi method was used to achieve consensus regarding the importance of statements that describe actions a helping professional can take to help a bereaved adolescent. Statements were compiled through a systematic search of the scientific and grey literature, and reviewing interview data from a recent related research study with bereaved adolescents, parents and counselors. An expert panel (N = 49) comprising 16 adolescents, 14 parents and 19 helping professionals, rated each statement. Statements that were endorsed by at least 80% of panellists were considered consensus recommendations.

Results
Panellists endorsed 130 out of 190 statements as appropriate actions. These included help for a bereaved adolescent being offered on an ongoing basis, with support to be provided flexibly to meet individual adolescent needs and to acknowledge the agency of the adolescent. Support after a loss by suicide should be tailored to address specific suicide-related issues. Parents of bereaved adolescents should also be offered support so that they are better equipped to help their bereaved adolescent.

Conclusions
This study identified consensus recommendations on how a helping professional might best help bereaved adolescents. It is hoped that these recommendations will guide helping professionals and enhance adolescent grief interventions.