bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in ABC Transporter Expression during Hematopoiesis Cause Lineage-Biased Cytopenias in Patients Treated with Aurora Kinase Inhibitors
Authors: Furlong Brooke A. , Posey Ryan R. , Chou David B. , Kyprianou Christos , O'Sullivan Lucy R. , David Rhiannon , Randle Suzanne , Polanska Urszula , Urosevic Jelena , Travers Jon , Hutchinson John , Hasserjian Robert P. , Prantil-Baun Rachelle , Ingber Donald E.
Published: November 2021

Chemotherapy-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While they are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecule drugs and the factors that determine the hematotoxicity profiles of chemotherapies are not fully understood. Here, we explore why Aurora kinase inhibitor drugs cause preferential neutropenia when compared to the cytopenic profiles of targeted small molecule cancer drugs that are FDA approved. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing published clinical datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibitors is acquired at an early stage of differentiation and is caused by developmental changes in the expression pattern of ATP-binding cassette (ABC) transporters. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some chemotherapies affect the bone marrow.

Disclosures

David: AstraZeneca: Current Employment. Randle: AstraZeneca: Current Employment. Polanska: AstraZeneca: Current Employment. Urosevic: AstraZeneca: Current Employment. Travers: AstraZeneca: Ended employment in the past 24 months. Ingber: Emulate: Membership on an entity's Board of Directors or advisory committees; BOA Biomedical: Membership on an entity's Board of Directors or advisory committees; Freeflow Medical Devices Inc: Membership on an entity's Board of Directors or advisory committees.
Outcomes after First Rescue Treatment in Patients with Relapsed or Refractory Multiple Myeloma in Colombia
Authors: Martinez-Cordero Humberto , Abello Virginia , Mantilla Duran William Armando , Gomez Rigoberto , Reyes Jheremy , Idrobo Henry , Galvez Kenny , Casas Claudia Patricia , Solano Maria Helena , Espinosa Daniel , Amar Ivan Alfredo Perdomo , Osuna Pérez Monica , Gomez Diaz Alvaro , Saavedra Domingo , Quintero Guillermo , Abenoza Lina , Gaviria Lina , Henao-Uribe Alicia , Sossa Claudia Lucia , Rosales Carmen , Paredes Claudia , Figueroa Emiliani Jair , Munevar Isabel , Bermudez Silva Carlos Daniel , Borjas Yasmin , Guerrero Alvaro , Guerrero Paola , Herrera Juan Manuel
Published: November 2021

Background Proteasome inhibitors (PIs) are approved for treating newly diagnosed and relapsed multiple myeloma (MM) in Colombia. This propensity score matching (PSM) analysis using data from the real-world, was designed to establish the role PIs (bortezomib or carfilzomib) at first relapsed or refractory MM. The primary endpoint was overall response rate (ORR) and secondary endpoint included was overall survival (OS). Moreover, an analysis of OS was done regarding response attained. On Behalf of RENEHOC-GRIMMCO (Colombian Registry for Hemato-Oncological Diseases and Colombian Mieloma Múltiple study group).

Methods PSM by nearest neighbor analysis to evaluate the role of PIs used at first relapse in multiple myeloma of patients belonging to RENEHOC registry, between 2010 and 2020.

Results 390 patients were identified in the first relapse of the Colombian registry, 269 patients with PI and 121 patients without PI. One hundred and ten patients were included in each group after PSM. Patients were matched for age, ISS, extramedullary disease, and use of lenalidomide to define the influence of this immunomodulatory drug in the PI group. A difference was found in the use of lenalidomide because only 1 patient was treated with PI and lenalidomide concomitantly (0.91%) compared to 31 patients in the group without PI (28.18%), (p <0, 0001).

Regarding ORR, no differences were found between the 2 groups 38.18% in PIs vs 37.27% in non-PIs group (p = 0.801). A trend towards better OS was found in the PIs group with a median of 58 months versus 39 months (p = 0.179). Overall survival in patients who achieved at least PR was better compared to those who did not reach 79 months versus 32 months in non-responders (p = 0.0001).

Conclusion In this study, we found that the use of PI has a tendency to improve overall survival in real-world in MM patients when used in the first relapse and that this effect could possibly be enhanced with the combination with lenalidomide. Regardless of the treatment used, better responses are associated with better survival.

Figure 1 Figure 1.

Disclosures

Abello: Janssen: Honoraria; Amgen: Honoraria; Dr Reddy's: Research Funding. Sossa: Amgen: Research Funding.
Metal-Ion Transporter SLC39A14 Is Required for Cardiac Iron Loading in the Hjv Mouse Model of Iron Overload
Authors: Liu Qingli , Azucenas Corbin , Mackenzie Bryan , Knutson Mitchell
Published: November 2021

Although iron overload-related cardiomyopathy is a leading cause of morbidity and mortality in iron-overload disorders (e.g., thalassemia major and hemochromatosis), the molecular mechanisms that mediate cardiac iron uptake and accumulation are incompletely understood. Previous studies using Slc39a14 knockout mice have revealed that SLC39A14 is required for the uptake of non-transferrin-bound iron (NTBI) by the liver and pancreas and is essential for iron loading of hepatocytes and pancreatic acinar cells. To investigate the requirement for SLC39A14 in cardiac iron accumulation, we generated cardiomyocyte-specific Slc39a14 knockout (Slc39a14 hrt/hrt) mice and crossed them with iron-loading hemojuvelin (Hjv) knockout mice to generate Hjv -/-;Slc39a14 hrt/hrt animals. At 12 and 24 weeks of age, cardiac nonheme iron levels were ~340% higher in Hjv -/- mice than in controls. By contrast, cardiac nonheme iron levels in Hjv -/-;Slc39a14 hrt/hrt mice at these ages were only ~60% higher than those than in controls, and ~65% less than those in Hjv -/- mice. Moreover, cardiac nonheme iron levels in Hjv -/-;Slc39a14 +/hrt (heterozygous conditional Slc39a14 knockout) mice were between those of Hjv -/- and Hjv -/-;Slc39a14 hrt/hrt mice, suggesting a gene-dosage effect of Slc39a14 on cardiac iron accumulation. A role for voltage-dependent calcium channels in mediating the uptake of NTBI into cardiomyocytes has been proposed based on observations of the effects of L-type calcium-channel blockers on iron uptake and accumulation in vitro and in vivo. We considered the possibility that these observations could be explained if SLC39A14 were reactive with calcium-channel blockers. To test this hypothesis, we examined the effects of blockers on the activity of SLC39A14 by using radiotracer assays in RNA-injected Xenopus oocytes expressing mouse SLC39A14. We found that 100 µM amlodipine (Amld), nifedipine, and nicardipine each afforded modest inhibition of SLC39A14-mediated 55Fe 2+. Inhibition of iron transport by Amld was dose-dependent, EC 50 = 167 µM ± (SEM) 30 µM. Our findings implicate SLC39A14 in mediating cardiomyocyte NTBI uptake in the mouse and raise doubts about the relative importance of calcium channels as a mechanism by which NTBI gains entry to the heart.

Disclosures

No relevant conflicts of interest to declare.
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

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<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<0.05). For OBWC, FV was an additional significant positive predictor (p<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

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

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

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

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

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

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

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

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

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

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.
Social determinants of health related to stay-at-home order adherence and social distancing attitudes among a diverse Deep South population
Authors: Lemacks Jennifer L. , Greer Tammy , Aras Sermin , Abbott Laurie , Willis Darlene , Gipson June , Elasri Mohamed O.
Published: November 2021

Objective

To describe COVID-19 related symptoms and medical care experienced in the first six months of the pandemic as well as stay-at-home order adherence, and attitudes related to COVID-19 risk and social distancing among a diverse sample of adults in the Deep South.

Methods

Survey data were collected from 411 Louisiana and Mississippi residents for three weeks in June 2020 through social media.

Results

Over half (52.5%) of participants who experienced COVID-19 related symptoms (with 41.5% experiencing at least one symptom) did not feel the severity of symptoms warranted seeking medical care. 91.6% of the Deep South adults visited certain places or did activities where visiting or gathering with other people was involved during stay-at-home mandates. Religiosity/spirituality, age, education, number of children in the home, attitudes related to COVID-19 risk of complications and social distancing were related to the greater/lesser likelihood of stay-at-home order adherence.

Conclusions

Various cultural and contextual factors were related to stay-at-home order adherence. Understanding how social values, life stage, socioeconomic, and geographic factors influence stay-at-home order adherence would lead to more effective policy design to improve population adherence.
Applicable safety analysis and biomechanical study of iliosacral triangular osteosynthesis
Authors: Zheng Jianxiong , Xiang Jie , Feng Xiaoreng , Liu Fei , Chen Keyu , Chen Bin
Published: November 2021

Background

The aim of this study was to investigate the applicable safety and biomechanical stability of iliosacral triangular osteosynthesis (ITO) through 3D modeling and finite element (FE) analysis.

Methods

Pelvic CT imaging data from 100 cases were imported into Mimics software for the construction of 3D pelvic models. The S2-alar-iliac (S2AI) screws and S2 sacroiliac screws were placed in the S2 segment with optimal distribution and their compatibility rate on the S2 safe channel was observed and analyzed. In the FE model, the posterior pelvic ring was fixed with two transsacral screws (TTS), triangular osteosynthesis (TO) and ITO, respectively. Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending, and left twisting, respectively. The relative displacement and change in relative displacement of the three fixing methods were recorded and analyzed.

Results

The theoretical compatibility rate of S2AI screw and S2 sacroiliac screw in S2 segment was 94%, of which 100% were in males and 88% in females. In the FE model, in terms of overall relative displacement, TTS group showed the smallest relative displacement, the ITO group showed the second smallest, and the TO group the largest relative displacement. The change in relative displacement of the TTS group displayed the smaller fluctuations in motion. The change in relative displacement of the TO group under right bending and left twisting displayed larger fluctuations, while the ITO group under flexion displayed larger fluctuations.

Conclusions

The simultaneous placement of S2AI screw and S2 sacroiliac screw in the S2 segment is theoretically safe. Although the biomechanical stability of ITO is slightly lower than TTS, it is better than TO, and can be used as a new method for the treatment of posterior pelvic ring injuries.
Providing lifestyle advice to women with PCOS: an overview of practical issues affecting success
Authors: Ee Carolyn , Pirotta Stephanie , Mousa Aya , Moran Lisa , Lim Siew
Published: November 2021

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting up to 13 % of women. Lifestyle interventions are first-line treatments, however attrition in women with PCOS is high. This review summarises current evidence on barriers to lifestyle management in PCOS and suggested strategies for overcoming these challenges, mapped to the Capability, Opportunity, Motivation and Behaviour model.

Physical capability for lifestyle changes may be impacted by altered gut hormone regulation and energy expenditure in PCOS. This may contribute to difficulties with weight management. The higher prevalence of eating disorders, disordered eating, fatigue and sleep disturbances are further barriers. Psychological capability may be reduced due psychological symptoms and lack of critical health literacy. Women with PCOS face similar challenges in terms of Opportunity to make lifestyle changes as other women of reproductive age. However, these are complicated by features more common in PCOS including body dissatisfaction. Motivation to adopt healthy lifestyles may be impacted by suboptimal risk perception and intrinsic motivation.

To address these barriers, screening for and management of eating disorders, disordered eating, depression, and Obstructive Sleep Apnoea should be undertaken as per international evidence-based guidelines. A weight-neutral approach may be appropriate with disordered eating. Building capability among health professionals to better partner with women with PCOS on their management is essential in addressing health literacy gaps. Behavioural strategies that target risk perception and build intrinsic motivation should be utilised. More research is required to understand optimal self-management strategies, risk perception, energy homeostasis and overcoming attrition in women with PCOS.
The effect of concha bullosa and nasal septal deviation on palatal dimensions: a cone beam computed tomography study
Authors: Shetty Shishir Ram , Al Bayatti Saad Wahby , Al-Rawi Natheer Hashim , Kamath Vinayak , Reddy Sesha , Narasimhan Sangeetha , Al Kawas Sausan , Madi Medhini , Achalli Sonika , Bhat Supriya
Published: November 2021

Introduction

Nasal septal deviation (NSD) and concha bullosa (CB) are associated with airway obstruction in mouth breathers. Mouth breathing is associated with alterations in maxillary growth and palatal architecture. The aim of our study was to determine the effect of the presence of CB and NSD on the dimensions of the hard palate using cone-beam computed tomography (CBCT).

Materials and methods

A retrospective study was conducted using CBCT scans of 200 study subjects. The study subjects were divided into four groups based on the presence of CB and NSD. Septal deviation angle (SDA), palatal interalveolar length (PIL), palatal depth (PD) and maxillopalatal arch angle (MPAA) were measured in the study groups.

Results

The presence of NSD and CB was associated with significant (p < 0.001) differences in the palatal dimensions of the study subjects. The PIL and MPA (p < 0.001) were significantly reduced (p < 0.001), whereas the PD was significantly increased (p < 0.001) in study subjects with NSD and CB. There was no significant change in the palatal dimensions between the unilateral and bilateral types of CB. Among the palatal dimensions, the PIL had the most significant association (R2 = 0.53) with SDA and CB. There was a significant correlation between the palatal dimensions and SDA when CB was present along with NSD.

Conclusion

Based on the results of this study, it can be concluded that the presence of NSD and CB have a significant effect on the palatal dimensions and, therefore, they may be associated with skeletal malocclusion.
Chlorophyll fluorescence as a light signal enhances iron uptake by the marine diatom Phaeodactylum tricornutum under high-cell density conditions
Authors: Liu Xuehua , Xie Xiujun , Gao Shan , Wang Lepu , Zhou Lu , Liu Yao , Hu Qiang , Gu Wenhui , Wang Guangce
Published: November 2021

Background

Diatoms usually dominate phytoplankton blooms in open oceans, exhibiting extremely high population densities. Although the iron uptake rate of diatoms largely determines the magnitude and longevity of diatom blooms, the underlying mechanisms regulating iron uptake remain unclear.

Results

The transcription of two iron uptake proteins, ISIP2a and ISIP1, in the marine diatom Phaeodactylum tricornutum was enhanced with increasing cell density, whereas the cellular iron content showed the opposite trend. When compared with the wild-type strain, knockdown of ISIP2a resulted in 43% decrease in cellular iron content, implying the involvement of ISIP2a in iron uptake under high-cell density conditions. Incubation of the diatom cells with sonicated cell lysate conditioned by different cell densities did not affect ISIP2a and ISIP1 expression, ruling out regulation via chemical cues. In contrast, ISIP2a and ISIP1 transcription were strongly induced by red light. Besides, chlorophyll fluorescence excited from the blue light was also positively correlated with population density. Subsequently, a “sandwich” illumination incubator was designed to filter out stray light and ensure that the inner layer cells only receive the emitted chlorophyll fluorescence from outer layers, and the results showed that the increase in outer cell density significantly elevated ISIP2a and ISIP1 transcription in inner layer cells. In situ evidence from Tara oceans also showed positively correlated between diatom ISIP transcripts and chlorophyll content.

Conclusions

This study shows that chlorophyll fluorescence derived from neighboring cells is able to upregulate ISIP2a and ISIP1 expression to facilitate iron assimilation under high-cell density. These results provide novel insights into biotic signal sensing in phytoplankton, which can help to elucidate the underlying mechanisms of marine diatom blooms.
ROB-MEN: a tool to assess risk of bias due to missing evidence in network meta-analysis
Authors: Chiocchia Virginia , Nikolakopoulou Adriani , Higgins Julian P. T. , Page Matthew J. , Papakonstantinou Theodoros , Cipriani Andrea , Furukawa Toshi A. , Siontis George C. M. , Egger Matthias , Salanti Georgia
Published: November 2021

Background

Selective outcome reporting and publication bias threaten the validity of systematic reviews and meta-analyses and can affect clinical decision-making. A rigorous method to evaluate the impact of this bias on the results of network meta-analyses of interventions is lacking. We present a tool to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN).

Methods

ROB-MEN first evaluates the risk of bias due to missing evidence for each of the possible pairwise comparison that can be made between the interventions in the network. This step considers possible bias due to the presence of studies with unavailable results (within-study assessment of bias) and the potential for unpublished studies (across-study assessment of bias). The second step combines the judgements about the risk of bias due to missing evidence in pairwise comparisons with (i) the contribution of direct comparisons to the network meta-analysis estimates, (ii) possible small-study effects evaluated by network meta-regression, and (iii) any bias from unobserved comparisons. Then, a level of “low risk”, “some concerns”, or “high risk” for the bias due to missing evidence is assigned to each estimate, which is our tool’s final output.

Results

We describe the methodology of ROB-MEN step-by-step using an illustrative example from a published NMA of non-diagnostic modalities for the detection of coronary artery disease in patients with low risk acute coronary syndrome. We also report a full application of the tool on a larger and more complex published network of 18 drugs from head-to-head studies for the acute treatment of adults with major depressive disorder.

Conclusions

ROB-MEN is the first tool for evaluating the risk of bias due to missing evidence in network meta-analysis and applies to networks of all sizes and geometry. The use of ROB-MEN is facilitated by an R Shiny web application that produces the Pairwise Comparisons and ROB-MEN Table and is incorporated in the reporting bias domain of the CINeMA framework and software.
Genomic medicine in the Middle East
Authors: Abou Tayoun Ahmad N. , Fakhro Khalid A. , Alsheikh-Ali Alawi , Alkuraya Fowzan S.
Published: November 2021

We discuss the current state of genomic medicine in Arab countries of the Middle East, a region with outsized contribution to Mendelian genetics due to inbreeding yet has poor representation in global variome datasets. We focus on genomic testing, clinical genetics, and genetic counseling services along with associated training and research programs. Finally, we highlight opportunities for improvement in genomic medicine services in this region.
Metabolic profiling of maize seeds with both insect- and herbicide-resistance genes (cry1Ab and epsps), dual herbicide-resistance genes (epsps and pat), and natural genotypic varieties
Authors: Liu Weixiao , Dong Mei , Meng Lixia , Wan Yusong , Jin Wujun
Published: November 2021

Background

Widely targeted metabolomics was applied to estimate the differences in the metabolite profiles of maize seeds from 3 natural genotypic varieties and 4 genetically modified (GM) lines.

Results

Pairwise comparison with their isogenic controls revealed 71, 121, 43 and 95 differentially accumulated metabolites (DAMs) in GM maize seeds of C0030.2.4, C0030.3.5, C0010.1.1 and C0010.3.1, respectively. KEGG pathway enrichment analysis showed that most of these DAMs participated in the biosynthesis of secondary metabolites and purine metabolism in GM maize C0030.2.4 and C0030.3.5, but participated in tryptophan metabolism and 2-oxocarboxylic acid metabolism in C0010.3.1 seeds and in metabolic pathways and the biosynthesis of secondary metabolites in C0010.1.1 seeds. The data also showed that the differences in metabolite accumulation, both total DAMs and co-DAMs, among the different natural genotypic varieties (418 DAMs and 39 co-DAMs) were greater than those caused by genetic modification (330 DAMs and 3 co-DAMs).

Conclusions

None of the DAMs were identified as new or unintended, showing only changes in abundance in the studied maize seeds. The metabolite profile differences among the 3 non-GM lines were more notable than those among GM lines. Different genetic backgrounds affect metabolite profiling more than gene modification itself.

Graphic abstract
Diversity of plants and mammals as indicators of the effects of land management types in woodlands
Authors: Szymañski Carolina R. , Tabeni Solana , Alvarez Juan A. , Campos Claudia M.
Published: November 2021

Background

The ecological indicators are useful tools to determine the effects of human disturbances on woodland biodiversity. Nevertheless, ecological indicators not always responded in the same way to disturbances, and the responses can differ among taxa. In arid and semiarid woodlands, the use of deadwood associated with cattle raising can affect biodiversity and Nature’s contributions to people.

Methods

Our study aimed to assess changes in taxonomic and functional diversity of two assemblages, plants and mammals, in Prosopis woodlands under different land management types: grazed woodlands and a protected area. For plants, changes in structural diversity were also analyzed. Prosopis trees under different land management types were selected and their deadwood characteristics were registered. Through live traps and camera traps, we obtained data on the presence-absence of mammals per tree to estimate diversity indices. For plants, we measured the abundance of vegetation by species and by cover type through the Line-Intercept Method to estimated diversity. Finally, we built generalized linear models to assess the responses of diversity of each assemblage to covariables concerning deadwood and different land management types.

Results

We found that all diversity indeces for plants were either negatively affected by the presence of deadwood on the ground, or favored by its extraction. For mammals, removal of deadwood increased taxonomic diversity, while functional diversity increased with deadwood on the trees. Both structural diversity of plants and functional diversity of mammals were greater in grazed woodlands.

Conclusions

The sustainable use of woodland resources is essential for the activities of rural communities. Our study results indicated that land management of grazed woodlands promoted the structural diversity of plant assemblages and the functional diversity of mammals. The presence of deadwood negatively affected plant diversity but it increased mammal functional diversity. It is advisable to maintain trees that preserve their wooden structure within the managed areas to promote the functional diversity of mammals, while trees with extraction from standing wood will favor the functional diversity of the plant assemblage. Understanding the effects of human disturbances can contribute to management for the conservation of woodlands diversity and Nature’s contributions to people.