bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Alzheimer’s disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration
Authors:   Alzheimer’s Disease Neuroimaging Initiative, Tan Meng-Shan , Yang Yu-Xiang , Xu Wei , Wang Hui-Fu , Tan Lin , Zuo Chuan-Tao , Dong Qiang , Tan Lan , Suckling John , Yu Jin-Tai
Published: January 2021

Background

Genome-wide association studies have identified more than 30 Alzheimer’s disease (AD) risk genes, although the detailed mechanism through which all these genes are associated with AD pathogenesis remains unknown. We comprehensively evaluate the roles of the variants in top 30 non-APOE AD risk genes, based on whether these variants were associated with altered mRNA transcript levels, as well as brain amyloidosis, tauopathy, and neurodegeneration.

Methods

Human brain gene expression data were obtained from the UK Brain Expression Consortium (UKBEC), while other data used in our study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We examined the association of AD risk allele carrier status with the levels of gene expression in blood and brain regions and tested the association with brain amyloidosis, tauopathy, and neurodegeneration at baseline, using a multivariable linear regression model. Next, we analyzed the longitudinal effects of these variants on the change rates of pathology using a mixed effect model.

Results

Altogether, 27 variants were detected to be associated with the altered expression of 21 nearby genes in blood and brain regions. Eleven variants (especially novel variants in ADAM10, IGHV1-68, and SLC24A4/RIN3) were associated with brain amyloidosis, 7 variants (especially in INPP5D, PTK2B) with brain tauopathy, and 8 variants (especially in ECHDC3, HS3ST1) with brain neurodegeneration. Variants in ADAMTS1, BZRAP1-AS1, CELF1, CD2AP, and SLC24A4/RIN3 participated in more than one cerebral pathological process.

Conclusions

Genetic variants might play functional roles and suggest potential mechanisms in AD pathogenesis, which opens doors to uncover novel targets for AD treatment.
Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing
Authors: Kong Lingchi , Wang Yan , Wang Haixing , Pan Qi , Zuo Rongtai , Bai Shanshan , Zhang Xiaoting , Lee Wayne Yukwai , Kang Qinglin , Li Gang
Published: January 2021

Background

Paracrine signaling from endothelial progenitor cells (EPCs) is beneficial for angiogenesis and thus promotes tissue regeneration. Microgravity (MG) environment is found to facilitate the functional potentials of various stem or progenitor cells. The present study aimed to elucidate the effects of MG on pro-angiogenic properties and fracture repair capacities of conditioned media (CM) from EPCs.

Methods

Human peripheral blood-derived EPCs were cultured under MG or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free CM under MG (MG-CM) or NG (NG-CM) were collected, and their pro-angiogenic properties were examined in human umbilical vein endothelial cells (HUVECs). In order to investigate the effects of MG-CM on fracture healing, they were injected into the fracture gaps of rat models, and radiography, histology, and mechanical test were performed to evaluate neovascularization and fracture healing outcomes.

Results

MG upregulated the expression of hypoxia-induced factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and promoted NO release. Comparing to NG-CM, MG-CM significantly facilitated the proliferation, migration, and angiogenesis of HUVECs through NO-induced activation of FAK/Erk1/2-MAPK signaling pathway. In addition, MG-CM were verified to improve angiogenic activities in fracture area in a rat tibial fracture model, accelerate fracture healing, and well restore the biomechanical properties of fracture bone superior to NG-CM.

Conclusion

These findings provided insight into the use of MG bioreactor to enhance the angiogenic properties of EPCs’ paracrine signals via HIF-1α/eNOS/NO axis, and the administration of MG-CM favored bone fracture repair.

Graphical abstract
A sex-stratified long-term clinical outcome analysis in coronary chronic total occlusion patients
Authors: Gong Xuhe , Zhou Li , Ding Xiaosong , Li Hongwei , Chen Hui
Published: January 2021

Background

Differences in outcomes for women and men after percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) patients remain controversial. Herein, we compared the clinical outcomes by sex in CTO patients undergoing PCI.

Methods

A total of 563 consecutive patients (19% women) who were diagnosed with CTO at a single center in China from June 2017 to December 2019 were included in this study. Three hundred patients were revascularized by PCI, and 263 were not revascularized. The clinical outcomes of these patients stratified by sex were examined. The primary endpoints included the risk of major adverse cardiovascular and cerebrovascular events (MACCE); the secondary endpoint was cardiac death; hazard ratios were generated using multivariable Cox regression.

Results

Women represented 19% of the cohort (107/563 patients). Women have lower mean body mass index (BMI) and abdominal circumference compared with men; however, the proportion of hypertension, diabetes, and previous coronary heart disease is higher in female patients. At 2-year follow-up, there were no differences between men and women for MACCE (15.8% vs 20.6%, p = 0.234) and cardiac death (3.1% vs 5.6%, p = 0.202). Predictors of CTO recanalization revealed that age < 65 years, absence of prior CABG, no history of DM, and non-triple vessel were predictors of CTO recanalization. Sex did not predict recanalization in this regression model. Successful CTO PCI was associated with reduced MACCE.

Conclusion

Our study suggests an equal benefit of CTO recanalization with a marked reduction in MACCE in women and men alike. Further dedicated studies are needed to confirm these findings.
The scope and nature of sexual orientation and gender identity and expression change efforts: a systematic review protocol
Authors: Kinitz David J. , Salway Travis , Dromer Elisabeth , Giustini Dean , Ashley Florence , Goodyear Trevor , Ferlatte Olivier , Kia Hannah , Abramovich Alex
Published: January 2021

Background

Sexual orientation and gender identity and expression change efforts (SOGIECE) are a set of scientifically discredited practices that aim to deny and suppress the sexual orientations, gender identities, and/or gender expressions of sexual and gender minorities (SGM). SOGIECE are associated with significant adverse health and social outcomes. SOGIECE continue to be practiced around the world, despite denouncements from professional bodies and survivors, as well as calls for legislative advocacy to prohibit SOGIECE and protect SGM. There are substantial gaps in the availability of consolidated international research to support and refine legislative proposals related to SOGIECE, including those currently underway to enforce bans in Canada and elsewhere.

We therefore propose the first systematic review of international data on SOGIECE that will outline the scope and nature of these practices worldwide. Specifically, we aim to estimate how many SGM have been exposed to SOGIECE, which sub-groups of SGM experience higher rates of SOGIECE, and how estimates of SOGIECE vary over time and place. In addition, we aim to describe when, where, how, and under what circumstances SGM are exposed to SOGIECE.

Methods

To locate an interdisciplinary swath of papers, nine (9) bibliographic databases will be searched: Medline (OVID), Embase (OVID), PsycInfo and Social Work Abstracts via EBSCO, CINAHL, Web of Science Core Collection, LGBTQ+ Source, and Proquest Dissertations & Theses Global and Sociology Collection (ProQuest). A gold standard search will be developed for Medline and adapted to the other databases. Grey literature will be searched at relevant websites, and reference harvesting will be performed in relevant SOGIECE scientific consensus statements. Two authors will independently screen abstracts/titles, screen full texts, abstract data, and apply risk of bias assessments. A narrative synthesis will be implemented to summarize findings.

Discussion

This review will address the gap in synthesized data regarding the prevalence of SOGIECE, social correlates of SOGIECE, variations of SOGIECE over time and place, and the circumstances, settings, and time-points of SOGIECE exposure. Findings from this review will directly inform ongoing and new legislative efforts to ban SOGIECE and other interventions that aim to stem SOGIECE practices and support SOGIECE survivors.

Systematic review registration

Registration with PROSPERO can be found under the registration number: CRD42020196393.
Bioassay-guided isolation and identification of anti-obesity phytochemicals from fruits of Amomum tsao-ko
Authors: Hong Seong Su , Choi Chun Whan , Lee Ji Eun , Jung Yeon Woo , Lee Jung A. , Jeong Wonsik , Choi Yun-Hyeok , Cha Hanna , Ahn Eun-Kyung , Oh Joa Sub
Published: January 2021

Amomum tsao-ko (Zingiberaceae), an important traditional medicinal herb, possesses many biological activities, including anti-inflammatory effects. Though the anti-obesity properties of the crude ethanol extract of A. tsao-ko fruits have been reported, the anti-adipogenic properties of its phytochemical constituents have not been reported. Therefore, in the present study, we isolated the active constituents of A. tsao-ko and investigated their anti-adipogenic effects. The bioassay-guided isolation of the phytochemicals from the ethanol extract of A. tsao-ko fruits identified four bioactive compounds, comprising one fatty acid (1), one sesquiterpene alcohol (2), and two phenolic compounds (3 and 4). Their structures were elucidated by a combination of 1D and/or 2D nuclear magnetic resonance and mass spectrometry. The anti-adipogenic activities of the four compounds evaluated by Oil Red O staining in 3T3-L1 cells revealed that the treatment with the isolated compounds 1 and 3 reduced the lipid accumulation in 3T3-L1 adipocytes more strongly than the compounds 2 and 4, in a dose-dependent manner.
Assessment of carbon stock potential of parkland agroforestry practice: the case of Minjar Shenkora; North Shewa, Ethiopia
Authors: Tsedeke Reta Eshetu , Dawud Seid Muhie , Tafere Solomon Mulu
Published: January 2021

Background

The anthropogenic global climate change has negative impacts on various sectors and communities who particularly rely on rain-fed agriculture. Parkland agroforestry practice can contribute to mitigate and adapt to the forthcoming climate change through carbon sequestration. However, empirical studies on carbon stocks potential of parklands agroforestry practices .

Methodology

By using two-stage stratified random sampling technique, 4 kebeles from two agro ecology were selected and 8 farms/plots/ of 40 m*40 m sample size were selected from each kebele for the vegetation inventory. Tree species-specific allometric equations were used to determine carbon stock potential of parkland agroforestry practice.

Results

The result reveal that, AGC, BGC, SOC and Total Carbon have significant variation (p < 0.05) across kebeles. The mean total carbon stock of Bolo Giorgis, Bolo Slase, Agirat and Korma Agere is 48.87 Mg C ha− 1, 58.21 Mg C ha− 1, 57.81 Mg C ha− 1and 73.71 Mg C ha− 1; respectively. On average, carbon stock of parklands practice in Minjar shenkora was 59.65 Mg C ha− 1.

Conclusions

The parkland agroforestry practice has a large potential to deliver regulating ecosystem services like opportunities to mitigate the impending climate-changing through carbon sequestration and increasing the resilience of the agricultural system at Minjar shenkora woreda. To enhance the multiple ecosystem services of the parkland agroforestry practices in sustainable way: local by-laws should be strengthened to avoid illegal tree cutting and free grazing.
Detecting medication errors associated with the use of beta-lactams in the Russian Pharmacovigilance database
Authors: Kuzmina Anna V. , Asetskaya Irina L. , Zyryanov Sergey K. , Polivanov Vitaliy A.
Published: January 2021

Background

Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs).

Methods

To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug.

Results

A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the “Adverse Reactions” section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the “Case narrative” section.

MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group.

Conclusion

Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the “Adverse Reactions” section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance.
Development of a sensitive and stable GC-MS/MS method for simultaneous determination of four N-nitrosamine genotoxic impurities in sartan substances
Authors: Liu Jie , Xie Bin , Mai Binliang , Cai Qiang , He Rujian , Guo Dong , Zhang Zhifeng , Fan Jun , Zhang Weiguang
Published: January 2021

Recently, N-nitrosamines have been unexpectedly found in generic sartan products. Herein, we developed a sensitive and stable GC-MS/MS method with multiple reactions monitoring mode for the simultaneous determination of four N-nitrosamines in sartan substances, namely, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, and N-nitrosodiisopropylamine. The conditions of gas chromatography and mass spectrometry were optimized. The method was validated according to the International Council for Harmonization guidelines in terms of sensitivity, linearity, accuracy, precision, specificity, and stability. The limits of detection of N-nitrosamines in sartan substances ranged from 0.002 to 0.150 ppm, and the corresponding limits of quantification were in the range of 0.008-0.500 ppm, which met the sensitivity requirements for the limits set by the Food and Drug Administration of the United States. The internal standard curve of four N-nitrosamines showed good linearity of regression coefficients over 0.99. The recoveries of N-nitrosamines in selected sartan drugs ranged from 87.68 to 123.76%. The intraday and interday relative standard deviation values were less than 9.15%. Therefore, this proposed method exhibited good sensitivity and precision, high accuracy, and fast analysis speed, which provide a reliable method for quality control of N-nitrosamines in sartan products.
Nomograms based on SUVmax of 18F-FDG PET/CT and clinical parameters for predicting progression-free and overall survival in patients with newly diagnosed extranodal natural killer/T-cell lymphoma
Authors: Li Hongyan , Shao Guozhu , Zhang Yajing , Chen Xiaomin , Du Chengcheng , Wang Kun , Gao Zairong
Published: January 2021

Background

The prognostic value of 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) is not well established. We aimed to develop nomograms for individualized estimates of progression-free survival (PFS) and overall survival (OS) in patients with ENKTL using 18F-FDG PET/CT parameters and clinical parameters.

Methods

A total of 171 patients with newly diagnosed ENKTL undergoing 18F-FDG PET/CT scanning were retrospectively analyzed. Nomograms were constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomograms were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The C-index, the area under receiver operating characteristic (ROC) curve (AUC), and decision curve analysis (DCA) were used to contrast the predictive and discriminatory capacities of the nomograms against with the International Prognostic Index (IPI) and Korean Prognostic Index (KPI).

Results

Multivariate analysis demonstrated that pretreatment SUVmax≥9.5, disease stage II and III-IV, elevated lactate dehydrogenase (LDH), and elevated β2-microglobulin (β2-MG) had the strongest association with unfavorable PFS and OS. In addition, hemoglobin (Hb) < 120 g/L had a tendency to be associated with PFS. Both nomogram models incorporated SUVmax, Ann Arbor stage, LDH, and β2-MG. The PFS nomogram also included Hb. The nomograms showed good prediction accuracies, with the C-indexes for PFS and OS were 0.729 and 0.736, respectively. The calibration plots for 3-year and 5-year PFS/OS reported good consistency between predicted and observed probabilities for survival time. The PFS and OS were significantly different according to tertiles of nomogram scores (p < 0.001). The C-index and AUCs of the nomograms were higher than that of IPI and KPI. Moreover, DCA showed that the predictive accuracy of the nomograms for PFS and OS were both higher than that of IPI and KPI.

Conclusions

This study established nomograms that incorporate pretreatment SUVmax and clinical parameters, which could be effective tools for individualized prognostication of both PFS and OS in patients with newly diagnosed ENKTL.
A graphene film interlayer for enhanced electrical conductivity in a carbon-fibre/PEEK composite
Authors: Leow Christopher , Kreider Peter B. , Notthoff Christian , Kluth Patrick , Tricoli Antonio , Compston Paul
Published: January 2021

Carbon-fibre reinforced composites are seeing increased deployment, especially in the aerospace industry, and the next-generation of these materials will need to meet demanding performance requirements beyond just specific strength. The incorporation of nanomaterials such as graphene into composites has great potential for enhancing electrical, thermal, and mechanical properties, which could then enable new capabilities such as built-in lightning strike protection and electromagnetic shielding. One major challenge is successful integration of nanomaterials into the composite during the manufacturing process especially for thermoplastic based composites. This work explores the spray deposition of exfoliated graphene in liquid suspensions for the nano-enhancement of electrical properties in carbon-fibre reinforced polyether ether keytone (PEEK) composites. Developed thin films were smooth with RMS roughness of 1.06 μm on Si substrates and RMS roughness of 1.27 μm on CF-PEEK tapes. The addition of 1.3 wt% graphene into the interlayers of CF-PEEK composites resulted in bulk electrical conductivity enhancement both in plane and through thickness of ~ 1100% and 67.5% respectively. This approach allows for pre-consolidation introduction of high-performance nanomaterials directly to thermoplastic prepregs which could open simple pathways for the in-situ manufacturing of carbon-fibre reinforced polymer nanocomposites.
Increased modifiable cardiovascular risk factors in patients with Takayasu arteritis: a multicenter cross-sectional study
Authors: dos Santos Alexandre Moura , Misse Rafael Giovani , Borges Isabela Bruna Pires , Gualano Bruno , de Souza Alexandre Wagner Silva , Takayama Liliam , Pereira Rosa Maria R. , Shinjo Samuel Katsuyuki
Published: January 2021

Background

Modifiable cardiovascular risk factors (MCRFs), such as those related to aerobic capacity, muscle strength, physical activity, and body composition, have been poorly studied in Takayasu arteritis (TAK). Therefore, the aim of the study was to investigate MCRFs and their relationships with disease status and comorbidities among patients with TAK.

Methods

A multicenter cross-sectional study was conducted between 2019 and 2020, in which 20 adult women with TAK were compared with 16 healthy controls matched by gender, age, and body mass index. The following parameters were analyzed: aerobic capacity by cardiopulmonary test; muscle function by timed-stands test, timed up-and-go test, and handgrip test; muscle strength by one-repetition maximum test and handgrip test; body composition by densitometry; physical activity and metabolic equivalent by IPAQ, quality of life by HAQ and SF-36; disease activity by ITAS2010 and NIH score; and presence of comorbidities.

Results

Patients with TAK had a mean age of 41.5 (38.0–46.3) years, disease duration of 16.0 (9.5–20.0) years, and a mean BMI of 27.7±4.5 kg/m2. Three out of the 20 patients with TAK had active disease. Regarding comorbidities, 16 patients had systemic arterial hypertension, 11 had dyslipidemia, and two had type 2 diabetes mellitus, while the control group had no comorbidities. TAK had a significant reduction in aerobic capacity (absolute and relative VO2 peak), muscle strength in the lower limbs, increased visceral adipose tissue, waist-to-hip ratio, reduced walking capacity, decreased weekly metabolic equivalent, and quality of life (P< 0.05) as compared to controls. However, there were no correlations between these MCRFs parameters and disease activity.

Conclusions

TAK show impairment in MCRFs; therefore, strategies able to improve MCRF should be considered in this disease.
Prevalence, demographics, and clinical characteristics of Latin American patients with spondyloarthritis
Authors: Citera Gustavo , Bautista-Molano Wilson , Peláez-Ballestas Ingris , Azevedo Valderilio F. , Perich Risto A. , Méndez-Rodríguez José A. , Cutri Mariel S. , Borlenghi Cecilia E.
Published: January 2021

Large epidemiologic and clinical estimates of spondyloarthritis (SpA) in Latin America are not available. In this narrative review, our goal was to descriptively summarize the prevalence and features of SpA in Latin America, based on available small studies. A review of peer-reviewed literature identified 41 relevant publications. Of these, 11 (mostly based on Mexican data) estimated the prevalence of SpA and its subtypes, which varied from 0.28 to 0.9% (SpA), 0.02 to 0.8% (ankylosing spondylitis), 0.2 to 0.9% (axial SpA), and 0.004 to 0.08% (psoriatic arthritis). Demographic and/or clinical characteristics were reported in 31 of the 41 publications, deriving data from 3 multinational studies, as well as individual studies from Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, Peru, Uruguay, and Venezuela. Data relating to treatment, disease manifestations (articular and extra-articular), and comorbidities were summarized across the countries. Available data suggest that there is a variability in prevalence, manifestations, and comorbidities of SpA across Latin America. Basic epidemiologic and clinical data are required from several countries not currently represented. Data relating to current treatment approaches, patient outcomes, and socioeconomic impact within this large geographic region are also needed.
An accurate frequency-domain model of water interaction with cylinders of arbitrary shape during earthquakes
Authors: Zhao Mi , Wang Xiaojing , Wang Piguang , Zhang Chao , Du Xiuli
Published: January 2021

An accurate frequency domain model is proposed to analyze the seismic response of uniform vertical cylinders with arbitrary cross section surrounded by water. According to the boundary conditions and using the variables separation method, the vertical modes of the hydrodynamic pressure are firstly obtained. Secondly, the three-dimensional wave equation can be simplified to a two-dimensional Helmholtz equation. Introducing the scaled boundary coordinate, a scaled boundary finite element (SBFE) equation which is a linear non-homogeneous second-order ordinary equation is derived by weighted residual method. The dynamic-stiffness matrix equation for the problem is furtherly derived. The continued fraction is acted as the solution of the dynamic-stiffness matrix for cylinder dynamic interaction of cylinder with infinite water. The coefficient matrices of the continued fraction are derived recursively from the SBFE equation of dynamic-stiffness. The accuracy of the present method is verified by comparing the hydrodynamic force on circular, elliptical and rectangle cylinders with the analytical or numerical solutions. Finally, the proposed model is used to analyze the natural frequency and seismic response of cylinders.
Atrial Fibrillation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
Authors: Chang Ellen K. , Chanson Dayana , Teh Jennifer Berano , Iukuridze Aleksi , Peng Kelly , Forman Stephen J. , Nakamura Ryotaro , Wong F. Lennie , Cai LiYing , Armenian Saro H.
Published: January 2021

PURPOSE

To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes.

METHODS

A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events.

RESULTS

The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality.

CONCLUSION

The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.
Provider-Level Variation in Treatment Planning of Radiation Oncology Procedures in the United States
Authors: Valle Luca F. , Chu Fang-I. , Yoon Stephanie M. , Kundu Palak , Venkat Puja , Gilchrist Travis , Steinberg Michael L. , Raldow Ann C.
Published: January 2021

PURPOSE:

Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them.

METHODS:

The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non–facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population.

RESULTS:

Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, P < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, P < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, P < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, P = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, P = .02).

CONCLUSION:

Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.
Comparing Clinician-Assessed and Patient-Reported Performance Status for Predicting Morbidity and Mortality in Patients With Advanced Cancer Receiving Chemotherapy
Authors: Wood William A. , Deal Allison M. , Stover Angela M. , Basch Ethan
Published: January 2021

PURPOSE:

Performance status (PS) is assessed during cancer treatment to determine clinical trial eligibility, appropriateness for treatment, and need for supportive care. There is rising interest for patients to report this information directly. We determined whether clinician- and patient-reported PS were equally associated with mortality and service utilization in patients with cancer.

METHODS:

A secondary analysis was conducted using data from an radiotherapy plus chemotherapy in which 441 patients with advanced cancer and clinicians reported PS using the Eastern Cooperative Oncology Group scale. Simple kappa statistics measured agreement between clinician-reported performance status (cPS) and patient-reported performance status (pPS). Associations of cPS and pPS with emergency department (ED) and hospital visits and overall survival were evaluated via Cox regression, competing risk regression, and Fisher's exact tests.

RESULTS:

cPS and pPS correlated weakly (kappa = 0.27). Both pPS and cPS were associated with survival, ED visits, and hospitalizations, but only cPS remained associated after adjustment (survival: HR, 1.75; P < .0001). The first available cPS predicted mortality more strongly than the first available pPS (HR for death, comparing PS ≥ 1 v 0: 2.05 for cPS and 1.41 for pPS). When pPS questionnaires were repeated over time and averaged, associations with outcomes were stronger as measured by AIC model fit. Both pPS and cPS were associated with EQ-5D subcomponents (eg, 75%-77% with no usual activity deficits for PS 0, v 42%-51% for PS ≥ 1).

CONCLUSION:

Both clinician-reported PS and patient-reported PS provide useful information and can be considered for clinical trials and routine care.
Noninvasive Detection of Polyclonal Acquired Resistance to FGFR Inhibition in Patients With Cholangiocarcinoma Harboring FGFR2 Alterations
Authors: Varghese Anna M. , Patel Juber , Janjigian Yelena Y. , Meng Fanli , Selcuklu S. Duygu , Iyer Gopakumar , Houck-Loomis Brian , Harding James J. , O’Reilly Eileen M. , Abou-Alfa Ghassan K. , Lowery Maeve A. , Berger Michael F.
Published: January 2021

PURPOSE

Fibroblast growth factor receptor (FGFR) 2 alterations, present in 5%-15% of intrahepatic cholangiocarcinomas (IHC), are targets of FGFR-directed therapies. Acquired resistance is common among patients who respond. Biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient. We studied circulating tumor DNA (ctDNA) as a less invasive means of potentially identifying genomic mechanisms of resistance to FGFR-targeted therapies.

MATERIALS AND METHODS

Serial blood samples were collected from eight patients with FGFR-altered cholangiocarcinoma for ctDNA isolation and next-generation sequencing (NGS) throughout treatment and at resistance to anti-FGFR–targeted therapy. ctDNA was sequenced using a custom ultra-deep coverage NGS panel, incorporating dual index primers and unique molecular barcodes to enable high-sensitivity mutation detection.

RESULTS

Thirty-one acquired mutations in FGFR2, 30/31 located in the kinase domain, were identified at resistance in six of eight patients with detectable ctDNA. Up to 13 independent FGFR2 mutations were detected per patient, indicative of striking genomic concordance among resistant subclones.

CONCLUSION

ctDNA could be an effective means to longitudinally monitor for acquired resistance in FGFR2-altered IHC. The numerous acquired genetic alterations in FGFR2 suggest frequent polyclonal mechanisms of resistance that cannot be detected from single-site tissue biopsies.
Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies
Authors: Mackley Michael P. , Fernandez Nicholas R. , Fletcher Benjamin , Woolcott Christy G. , Fernandez Conrad V.
Published: January 2021

PURPOSE

Phase I trials are a crucial step in the evaluation of new cancer therapies. Historically, low rates of response (5%) and comparably high rates of death from toxicities (0.5%) have contributed to debates on the ethics and orientation of these trials. With the introduction of novel targeted therapies, a contemporary estimate is needed.

METHODS

We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of phase I oncology trials of single-agent targeted immunomodulators, molecularly targeted therapies, and antiangiogenic agents, published between January 2015 and July 2018. Adult and pediatric trials of solid and hematological malignancies were eligible. Treatment-related adverse events (grades 3, 4, and 5) and response rates (objective, complete, and partial) were extracted and analyzed.

RESULTS

One hundred and fifty-eight trial reports, covering 6,707 patients, were included. The rate of treatment-related deaths was 0.0% (95% CI, 0.0 to 0.1), while 13.2% of patients (9.5 to 17.3) experienced a grade 3 or 4 treatment-related toxicity. The combined objective response rate was 6.4% (4.6 to 8.5). Among trials using tumor biomarkers as eligibility criteria, the objective response rate was higher (12.0% [7.3 to 17.6] compared to 4.9% [2.5 to 5.7], P value < .01). The same was true of trials focusing on a single tumor type (13.4% [8.2 to 19.4]) compared to multiple tumor types (3.8% [2.5 to 5.3], P value < .01).

CONCLUSION

Reduced grade 5 risk and improved benefit appears to exist in modern phase I oncology trials, particularly in trials that target single tumor types and integrate biomarkers as eligibility criteria. These findings provide information to support informed consent discussions, highlight the need for improved reporting of phase I oncology trials, and provide direction for optimizing their design.
Variation in alarm calls during different breeding stages of the common kestrel (Falco tinnunculus)
Authors: Huo Xiaona , Zhou Lei , Feng Jiang , Wu Hui
Published: January 2021

Acoustic signals play a key role in animal communication. Animals usually use alarm signals to warn mates or offspring of the presence of threats or to intimidate or distract predators. Birds commonly use acoustic signals as a means of communication. Alarm calls in passerines at different breeding stages can reflect their nest defense intensity. However, little is known about the characteristics, plasticity, and impact factors of alarm calls during the reproductive period in raptors. Here, from March to July in 2019, the alarm calls of eight pairs of common kestrels (Falco tinnunculus) during the breeding period were recorded using a portable recorder with a strongly directed microphone in the Zuojia Nature Reserve, Jilin province, China. The differences in acoustic parameters of parental alarm calls in different breeding stages were analyzed. The results showed that the alarm calls of common kestrels were composed of multi-harmonic arched frequency modulation with the maximum energy distribution in the second harmonic. The duration and rate of the alarm calls increased significantly as the breeding season progressed, showing that parents spent increasing amounts of time on nest defense. Additionally, the acoustic parameters of alarm calls in common kestrels were significantly different depending on offspring numbers, suggesting that offspring numbers influenced parental nest defense. These results showed that differences in alarm calls during different breeding stages may reflect a trade-off between defense costs and reproductive benefits.
Polarisome assembly mediates actin remodeling during polarized yeast and fungal growth
Authors: Xie Ying , Miao Yansong
Published: January 2021

Dynamic assembly and remodeling of actin is critical for many cellular processes during development and stress adaptation. In filamentous fungi and budding yeast, actin cables align in a polarized manner along the mother-to-daughter cell axis, and are essential for the establishment and maintenance of polarity; moreover, they rapidly remodel in response to environmental cues to achieve an optimal system response. A formin at the tip region within a macromolecular complex, called the polarisome, is responsible for driving actin cable polymerization during polarity establishment. This polarisome undergoes dynamic assembly through spatial and temporally regulated interactions between its components. Understanding this process is important to comprehend the tuneable activities of the formin-centered nucleation core, which are regulated through divergent molecular interactions and assembly modes within the polarisome. In this Review, we focus on how intrinsically disordered regions (IDRs) orchestrate the condensation of the polarisome components and the dynamic assembly of the complex. In addition, we address how these components are dynamically distributed in and out of the assembly zone, thereby regulating polarized growth. We also discuss the potential mechanical feedback mechanisms by which the force-induced actin polymerization at the tip of the budding yeast regulates the assembly and function of the polarisome.
Boosting Ammonia Synthesis under Mild Reaction Conditions by Precise Control of the Basic Oxide–Ru Interface
Authors: Sato Katsutoshi , Nagaoka Katsutoshi
Published: January 2021

Strong basic oxide–supported Ru catalysts are easily prepared and handled, and they have been used as effective catalysts for ammonia synthesis under mild reaction conditions since the 1970s. Recent research has revealed that precise control of the boundary states between the basic oxide (i.e., rare-earth oxide, alkali earth oxide), oxygen defect sites, and Ru nanoparticles can be used to enhance ammonia synthesis under mild reaction conditions and inhibit hydrogen poisoning, which is a typical drawback of strong basic oxide–supported Ru catalysts.
Lithium-, Sodium-, and Potassium-ion Conduction in Polymeric and Discrete Coordination Systems
Authors: Yoshinari Nobuto , Konno Takumi
Published: January 2021

Coordination compounds have been increasingly studied as a new class of promising candidates for the matrix of ionic conducting materials because of their designability and high crystallinity. The ionic conduction of light alkali metal ions (Li+ and Na+) has been developed in polymeric coordination systems, which are commonly used under nonaqueous conditions. Recent studies have shown that discrete coordination compounds, as well as hydrated polymeric coordination compounds, can function as excellent ionic conductors even for heavier K+.
Transition-metal Complexes with Triple Bonds to Si, Ge, Sn, and Pb and Relevant Complexes
Authors: Hashimoto Hisako , Nagata Koichi
Published: January 2021

Transition-metal complexes featuring triple bonds to heavier Group 14 elements (Si, Ge, Sn, and Pb), which have long been synthetic challenges in organometallic chemistry, have been synthesized in the last few decades. In this highlight, synthetic methods for numerous kinds of complexes and their structural properties are overviewed. Application leading to new multiple bonded systems with M≡Ge–Ge≡M, M≡Si–M, and M=Si=M linkages, and to relevant metallotetrylenes are also highlighted.
Risk of vertebral fractures: evaluation on vertebral trabecular attenuation value and hydroxyapatite concentration in patients by chest spectral CT
Authors: Ma Qiang , Hou Xinmeng , Cheng Xiaoyue , You Yuangang , Yang Zhenghan , Ma Daqing , Wang Zhenchang
Published: January 2021

Objectives:

To analyze vertebral fractures risk in patients with chest scans by evaluating vertebral hydroxyapatite concentration measured on spectral CT compared to trabecular attenuation value measured on conventional CT.

Methods:

Our retrospective study reviewed CT of 216 patients. Analysis of vertebral (T11 – L1) hydroxyapatite concentration by spectral imaging and trabecular attenuation value by conventional CT imaging were performed in patients with chest CT examinations. Specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were performed by using receiver operating characteristic (ROC) curves in patients with and without vertebral fractures.

Results:

In male patients, vertebral hydroxyapatite concentration had high area under the ROC curve (0.916), by using the optimal threshold of 72.27 mg/cm3, specificity, sensitivity, NPV, and PPV were 91.7, 80.2, 36.7, and 98.7%, respectively. In female patients, vertebral hydroxyapatite concentration also had high area under the ROC curve (0.870), by using the optimal threshold of 74.79 mg/cm3, specificity, sensitivity, NPV, and PPV were 100.0, 77.8, 47.4, and 100.0%, respectively. Area under the ROC curve was significantly different between spectral CT-measured bone hydroxyapatite concentration and conventional CT-measured attenuation value in distinguishing vertebral fractures (p = 0.007 for males; p = 0.005 for females).

Conclusions:

Quantitative assessment with spectral CT may appear as higher accuracy than that of conventional CT imaging to analyze risk of vertebral fractures. Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.

Advances in knowledge:

Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.
Reference intervals for complete blood count from Umbilical Cord Blood in newborns and comparison with Venous Blood Values
Authors: Gündüz Mehmet , Temel Hayrettin
Published: January 2021

Background and Objective: Umbilical cord blood which can be obtained by a non-invasive method can be informative about the clinical status of the newborn. It was aimed to establish reference intervals for umbilical cord blood parameters, and to compare complete blood count results between umbilical cord and venous blood samples in this study.

Methods: This study was conducted at Medipol University Sefaköy Hospital, Department of Pediatrics, Istanbul, Turkey. A total of 1898 newborns who were born in a two-year period between January 2018 and December 2019 were included in the study. Venous blood samples were taken from 184 of them, and umbilical cord blood samples were taken from 1714 newborns.

Results: The percentiles were determined according to gender and delivery method for the hematological parameters of umbilical cord blood. While mean platelet, eosinophil and mean corpuscular volume values ​​were similar between the groups (p>0.05 for each), and significant differences were found between the groups in terms of all other mean hematological parameters ​​(p<0.05 for each).

Conclusion: The results of the complete blood count of umbilical cord blood samples can provide reliable information about the newborn. There are significant differences between umbilical cord and venous blood samples in terms of hematological parameters. For these reasons, it is necessary to determine reliable value ranges for umbilical cord blood hematological parameters in newborns. Data of our study can be a guide for further studies and clinicians.

doi: https://doi.org/10.12669/pjms.37.2.2526

How to cite this:Gunduz M, Temel H. Reference intervals for complete blood count from Umbilical Cord Blood in newborns and comparison with Venous Blood Values. Pak J Med Sci. 2021;37(2):439-444. doi: https://doi.org/10.12669/pjms.37.2.2526

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A systematic review on the effects of high frequency chest wall compression and intrapulmonary percussive ventilation in patients with neuromuscular disease
Authors: Giacomino Katia , Hilfiker Roger , Magnin Tina , Allet Lara
Published: January 2021

Background: Respiratory insufficiency is the most common cause of mortality among patients with a neuromuscular disease.

Methods: We explored the effects of high frequency wall compression and intrapulmonary percussive ventilation, compared with standard care or no treatment, on the lung volume and capacity, and quality of life in patients with neuromuscular disease during respiratory infections or in stable periods. We further assessed the effects of these two interventions on clinical value, complications, and survival. The literature search was performed on Embase, MEDLINE, CINAHL, CENTRAL and PEDro. Randomised controlled trials and cross-over studies were eligible.

Results: Five studies were included, and results were presented narratively. High frequency wall compression was not shown to be superior to standard care in terms of lung volume and capacity, quality of life, complications, and survival rate. Compared with standard care, intrapulmonary percussive ventilation showed non-significant differences in terms of lung volume and capacity, and the risk of respiratory infection. Standard care was nevertheless associated with a significantly higher risk of days of hospitalisation (Incidence Rate Ratio 8.5 [1.1-67]) and of antibiotic use than intrapulmonary percussive ventilation (Incidence Rate Ratio 43 [6-333]).

Conclusions: Due to large variety of reported outcomes, missing data and limited number of studies, no meta-analysis could be conducted. The results should be interpreted with caution as the results have a very low certainty of evidence and reported outcomes have a high risk of bias. The evidence for high frequency wall compression and intrapulmonary percussive ventilation is still insufficient to draw final conclusions.

Protocol registration: PROSPERO ID: CRD42017064703.
How ObGyns can best work with radiologists to optimize screening for patients with dense breasts
Authors: Etkin-Kramer Elizabeth , Albright DaCarla M. , Pushkin JoAnn
Published: January 2021

Discussions with patients around breast cancer screening typically rest
on the shoulders of ObGyns. When a patient is informed she has dense
breasts, what should your dialogue include, and what resources are
available to you?
APLICANDO A DECOMPOSIÇÃO EM VALORES SINGULARES NO PROCESSAMENTO DE IMAGENS
Authors: Furtado Danilo Pinheiro , De Faria Cristiane Oliveira , Sasaki Diana
Published: January 2021

Neste trabalho, investigamos a decomposição em valores singulares (SVD) em processamento de imagens, apresentando aplicações em dois  tópicos  desta área:  compressão e autenticação de imagens.