bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation Analysis between Household Hygiene and Sanitation and Nutritional Status and Female Leprosy in Gresik Regency
Authors: Prakoeswa Flora Ramona Sigit , Ilhami Afik Zakie , Luthfia Ratna , Putri Aviola Syania , Soebono Hardyanto , Husada Dominicus , Notobroto Hari Basuki , Listiawan Muhammad Yulianto , Endaryanto Anang , Prakoeswa Cita Rosita Sigit , Burkhart Craig G.
Published: September 2020

Leprosy, also known as morbus Hansenʼs disease, is a chronic disease caused by M. leprae. Leprosy attacks various parts of the body including nerves and skin. The most important factor in the occurrence of leprosy is the sources of transmission and contact, both from patients and the environment. Household conditions where the person lives and the nutritional status of the individual can be a risk factor for leprosy. Household hygiene and sanitation can be seen from several aspects, like the physical environment of the house, clean water facilities, personal hygiene, availability of latrines, waste disposal facilities, and garbage disposal. This study was aimed to determine the correlation between household hygiene sanitation and nutritional status with females with leprosy in Gresik Regency. This case-control study was conducted in December 2019 in Gresik Regency. The subjects of this study were 74 respondents taken by consecutive sampling techniques. Retrieval of data was carried out using observations from the healthy house component questionnaire, personal hygiene questionnaire, and direct measurement. Data were analyzed using the chi-square test. The results showed significant correlation between physical environment of the house (

p
=
0.001

, OR = 0.104), clean water facilities (

p
=
0.008

, OR = 0.261), availability of latrines (

p
=
0.018

, OR = 0.209), waste disposal facilities (

p
=
0.015

, OR = 0.291), and personal hygiene (

p
=
0.001

, OR = 2.850) and female leprosy in Gresik Regency. There is no correlation between nutritional status (

p
=
0.085

, OR = 0.422) and wastewater disposal waste (

p
=
0.183

, OR = 0.486) and female leprosy in this study.
Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis
Authors: Li Shu-ying , Zhao Ya-ling , Yang Yu-fan , Wang Xi , Nie Min , Wu Xue-yan , Mao Jiang-feng , Veglio Franco
Published: September 2020

Background. Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective. A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods. We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results. A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and

P
=
0.006

) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and

P
<
0.0001

). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and

P
=
0.002

) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and

P
<
0.0001

). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and

P
<
0.00001

) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and

P
=
0.0005

). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions. TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.
Periodic Microstrip Leaky Wave Antenna with Double-Sided Shorting Pins and Pairs of Slots
Authors: Chen Yahuan , Wang Kuang , Li Yuanxin , Long Yunliang
Published: October 2020

A backward to forward scanning periodic microstrip leaky wave antenna (MLWA) is presented. The proposed antenna consists of a long rectangular patch with alternating shorting pin on each side, which connects the antenna patch and the ground plane to form periodic shorting circuits. There are two pairs of slots alternately spaced on the long patch to suppress the open stop band (OSB). The OSB problem was initially reduced by optimizing the structural parameters, and the slotting on the patch further improved it. The measured radiation pattern in the y-z plane shows that the antenna can scan electronically from 142° to 39° toward the end-fire (+z direction) when the operating frequency changes from 6 GHz to 12.9 GHz. The measured gain is greater than 5 dBi over the entire operating band.
Elevated Serum Ceruloplasmin Levels Are Associated with Higher Impulsivity in People with Parkinson’s Disease
Authors: Bakeberg Megan C. , Riley Maddeson , Byrnes Michelle , Jefferson Alexa , Ghosh Souyma , Horne Malcom K. , McGregor Sarah , Stell Rick , Walters Sue , Evans Tess , Roberts Katherine , Mastaglia Frank L. , Anderton Ryan S.
Published: October 2020

Background. Heightened impulsivity has been reported in a subset of people with Parkinson’s disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. Objectives. To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP. Methods. The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores. Results. Serum ceruloplasmin was higher in females with PD (p<0.001) and associated with MDS-UPDRS III, Hoehn and Yahr, and ACE-R scores (p<0.05). When correcting for covariates, higher serum ceruloplasmin concentrations were associated with the 2nd order nonplanning impulsivity and with the 1st order self-control and cognitive complexity impulsivity domains. Conclusions. Higher serum ceruloplasmin levels are independently associated with heightened nonplanning impulsivity in PwP. Thus, serum ceruloplasmin levels may have clinical utility as a marker for heightened impulsivity in PD.
Bioinformatics-Based Identification of a circRNA-miRNA-mRNA Axis in Esophageal Squamous Cell Carcinomas
Authors: Wang Zhaojun , Li Haifeng , Li Fajun , Su Xin , Zhang Junhang , Silvestris Nicola
Published: September 2020

Background. Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to the lack of early disease symptoms. Using bioinformatics tools, this study aimed to discover differentially expressed nonprotein-coding RNAs and genes with potential prognostic relevance in ESCC. Methods. Two microRNAs (miRNAs) and one circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression of miRNAs (DEMs) and circRNAs (DECs) was, respectively, identified in ESCC tissue and compared to adjacent healthy tissue. Further analysis was performed using the miRNA microarray datasets, where miRTarBase was used to predict which messenger RNAs (mRNAs) was present. This was followed by protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses. Moreover, cytoHubba and UALCAN were used to predict the important nodes and perform patient survival analysis, respectively. The miRNA-associated circRNAs were predicted using the ENCORI website. The interaction between DECs and the predicted circRNAs was also determined. A circRNA-miRNA-mRNA axis was constructed. Results. Associated with RAP1B and circ_0052867, two miRNAs (miR-133b and miR-139-5p) were identified as being differentially expressed and downregulated across the two datasets. Finally, the circ_0052867/miR-139-5p/RAP1B regulatory axis was established. Conclusion. This study provides support for the possible mechanisms of disease progression in ESCC.
A New Elastoplastic Time‐History Analysis Method for Frame Structures
Authors: Liang Qianqian , Zhao Chen , Hu Jun
Published: October 2020

This study aimed to analyze the formation and application of the time‐domain elastoplastic response spectrum. The elastoplastic response spectrum in the time domain was computed according to the trilinear force‐restoring model. The time‐domain elastoplastic response spectrum corresponded to a specific yield strength coefficient, fracture stiffness, and yield stiffness. However, the force‐restoring models corresponding to different structural systems and the states of the structural systems at different moments were not the same. Therefore, the dynamic characteristics of a particular periodic point corresponding to a particular structure were meaningful for the elastoplastic response spectrum. In addition, the curve in the time‐domain dimension along the periodic point truly reflected the real‐time response of the structure when the structure encountered a seismic load.
Green Synthesis and Antibacterial Activity of HAp@Ag Nanocomposite Using Centella asiatica (L.) Urban Extract and Eggshell
Authors: Pham Xuan Nui , Nguyen Hoa Thi , Pham Ngan Thi
Published: October 2020

In recent years, the green synthesis of nanoparticles via biological processes has attracted considerable attention. Herein, we introduce a facile and green approach for the synthesis of poriferous silver nanoparticles (Ag-NPs) decorated hydroxylapatite (HAp@Ag) nanoparticles with excellent antibacterial properties. All the nanocomposites were fully characterized in the solid state via various techniques such as X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectrometer (EDX), in which the synthesized Ag-NPs (24 nm in diameter) and their homogeneous incorporation on HAp have been studied by ultraviolet-visible (UV-vis) technique, transmission electron microscopy (TEM), and dynamic light scattering (DLS) analysis. The obtained results indicate that the structure and morphology of HAp have no significant changes after the incorporation of Ag-NPs on its surface. Moreover, an impressive antibacterial activity of HAp@Ag nanocomposite against Gram-positive bacterium Staphylococcus aureus and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa has been recorded by using the agar well diffusion method. As a result, the HAp@Ag nanocomposite promises to be a great biomedical material with high antibacterial properties.
A DEA-Based Complexity of Needs Approach for Hospital Beds Evacuation during the COVID-19 Outbreak
Authors: Nepomuceno Thyago C. C. , Silva Wilka M. N. , Nepomuceno Késsia T. C. , Barros Isloana K. F.
Published: October 2020

Data envelopment analysis (DEA) is a powerful nonparametric engineering tool for estimating technical efficiency and production capacity of service units. Assuming an equally proportional change in the output/input ratio, we can estimate how many additional medical resource health service units would be required if the number of hospitalizations was expected to increase during an epidemic outbreak. This assessment proposes a two-step methodology for hospital beds vacancy and reallocation during the COVID-19 pandemic. The framework determines the production capacity of hospitals through data envelopment analysis and incorporates the complexity of needs in two categories for the reallocation of beds throughout the medical specialties. As a result, we have a set of inefficient healthcare units presenting less complex bed slacks to be reduced, that is, to be allocated for patients presenting with more severe conditions. The first results in this work, in collaboration with state and municipal administrations in Brazil, report 3772 beds feasible to be evacuated by 64% of the analyzed health units, of which more than 82% are moderate complexity evacuations. The proposed assessment and methodology can provide a direction for governments and policymakers to develop strategies based on a robust quantitative production capacity measure.
Progressive Failure and Fracture Mechanism of Sandstone under Hydraulic-Mechanical Coupling
Authors: Li Yingming , Liu Gang , Qin Tao , Jin Zhupeng , Zhao Chengxing , Huang Shunjie
Published: October 2020

Hydraulic coupling often leads to progressive rock failure accidents. Mechanical tests were performed over a range of combined pore water pressure and confining pressure stress path conditions to study the progressive failure characteristics of sandstone under hydraulic-mechanical coupling and explore the crack initiation and pore water fracture mechanism. The closure stress and damage stress were determined by the axial deformation stiffness and volume deformation stiffness. The experimental results indicate that confining pressure is the main controlling factor in the crack propagation stage, and pore water pressure enhances crack evolution. With increasing effective confining pressure, the effective peak deviatoric stress strongly increases and the characteristic stress increases linearly. The initiation stress and damage stress decrease with increasing pore water pressure. The moduli in stages I, II, and III are similar to the law of the transverse and radial deformation ratio with notable differences in stage IV. The fracture trend angle was determined by the ratio of axial crack strain and radial crack strain. Compared with the experimental results, the internal cracks in the sandstone samples are mainly type-II cracks, and type-I cracks are also locally present. After stress damage, the cracks expand and extend at an angle close to the real fracture.
Ultrasonic Spectrum Analysis of Granite Damage Evolution Based on Dry‐Coupled Ultrasonic Monitoring Technology
Authors: Liu Yang , Qiao Lan , Li Yuan , Ma Guodong , Golosov Andrei M.
Published: September 2020

The self‐developed dry‐coupled rock ultrasonic monitoring system is adopted to set up a multidirectional and multiwaveform ultrasonic monitoring network, which aims to analyse the evolution law of acoustic spectrum parameters in the process of granite loading failure under uniaxial compression, to explore the dominant acoustic spectrum characteristic information at different stages of granite loading, and to verify in situ the damage monitoring of time‐effect deformation. The results show that the wave velocity, amplitude, and amplitude‐frequency of the first wave and the velocity of P‐wave and S‐wave show a significant upward trend in the rock compaction section. After entering the elastic stage, the three spectral parameters become peacefully stable, and the stage transformation is obvious. In the stable crack growth stage, with the initiation of the crack, the dominant frequency of S‐wave shows a significant stage transition compared with the global ultrasonic wave velocity and the first arrived amplitude, and the dominant frequency decreases by 6%. In the unstable crack growth stage, the three acoustic spectrum parameters present obvious downward trend, and the first arrived wave amplitude of S‐wave is found to have a significant decline of 39.1%. On the eve of failure, the amplitude‐frequency of S‐wave shows different feature from the P‐wave; that is, S‐wave transfers from the state of multipeak in wide frequency to the state of single peak in low frequency, which is the failure precursor of the rock sample.
Experimental Investigation on Short Concrete Columns Reinforced by Bamboo Scrimber under Axial Compression Loads
Authors: Lei Min , Wang Zihao , Li Penghui , Zeng Liyi , Liu Hongyao , Zhang Zhidong , Su Huicheng
Published: September 2020

The paper presents bamboo scrimber bars as a reinforcing material instead of steel reinforcement in low‐strength concrete columns. Twelve short concrete columns with different reinforcements are tested under axial compression load to study the axial compressive behavior of short concrete columns reinforced by bamboo scrimber. Three columns are reinforced concrete columns, and the other nine columns are bamboo scrimber reinforced concrete columns. The failure process, bearing capacity, axial deformation, and strain of the specimens are compared and analyzed. The results show that the bonding performance between the bamboo scrimber bars by surface treatment and low‐strength concrete is excellent. In low‐strength concrete columns, the material properties of bamboo bars play more thoroughly than those of steel bars. When the bamboo reinforcement ratio is increased, the concrete column ductility is significantly improved, but the bearing capacity of the concrete column is not increased. The bamboo scrimber bars with the size of 10 mm × 10 mm or 15 mm × 15 mm can be used as longitudinal bars of low‐strength concrete columns. The ductility of the short concrete column with 2.56% bamboo scrimber reinforcement is close to that of the short concrete column with 0.72% steel reinforcement.
A Novel Robust Principal Component Analysis Algorithm of Nonconvex Rank Approximation
Authors: Zhu E. , Xu M. , Pi D.
Published: October 2020

Noise exhibits low rank or no sparsity in the low-rank matrix recovery, and the nuclear norm is not an accurate rank approximation of low-rank matrix. In the present study, to solve the mentioned problem, a novel nonconvex approximation function of the low-rank matrix was proposed. Subsequently, based on the nonconvex rank approximation function, a novel model of robust principal component analysis was proposed. Such model was solved with the alternating direction method, and its convergence was verified theoretically. Subsequently, the background separation experiments were performed on the Wallflower and SBMnet datasets. Furthermore, the effectiveness of the novel model was verified by numerical experiments.
Inverse Analysis of the Partitioning Deformation Modulusof High‐Arch Dams Based on Quantum Genetic Algorithm
Authors: Zhu Yantao , Niu Xinqiang , Wang Jimin , Gu Chongshi , Zhao Erfeng , Huang Lixian
Published: September 2020

The physical and mechanical parameters of hydraulic structures in complicated operating conditions often change over time. Updating these parameters in a timely manner is important to comprehend the operating behaviors and monitor the safety of hydraulic structures. Conventional inverse analysis methods can only generate inversions on the comprehensive deformation modulus of concrete dam structures, which contradict practical conditions. Based on the researches on conventional reversion methods of the deformation modulus of the dam body, foundation, and reservoir basin, the objective fitness function is established in this paper according to engineering‐measured data and finite element simulation results. The quantum genetic algorithm has high global search efficiency and population diversity. A mechanical parameter inversion of high‐arch dams is built from the intelligent optimization of an established algorithm by applying the quantum genetic algorithm. The proposed algorithm is tested to be feasible and valid for practical engineering projects and therefore shows scientific and practical application values.
Splenic Hematopoietic and Stromal Cells in Cancer Progression
Authors: Steenbrugge Jonas , De Jaeghere Emiel A. , Meyer Evelyne , Denys Hannelore , De Wever Olivier
Published: September 2020

Tumor-derived secretory factors orchestrate splenic hematopoietic and stromal cells to fuel metastasis. The spleen acts as a reservoir site for hematopoietic stem and progenitor cells, which are rapidly exploited as myeloid-derived suppressor cells at the cost of tumor-reactive lymphoid cells. Splenic erythroid progenitor cells and mesenchymal stromal cells contribute directly and indirectly to both tumor immune escape and the metastatic cascade. Animal models provide valuable mechanistic insights, but their translation to a clinical setting highlights specific challenges and open issues. In this review, we envision the exploitation of the spleen as a source for novel biomarkers and therapeutic approaches.
Development of Helicobacter pylori Whole-Proteome Arrays and Identification of Serologic Biomarkers for Noncardia Gastric Cancer in the MCC-Spain Study
Authors: Jeske Rima , Reininger Dennis , Turgu Busra , Brauer Amber , Harmel Christoph , Fernández de Larrea-Baz Nerea , Martín Vicente , Moreno Victor , Kogevinas Manolis , Pollán Marina , Hoheisel Jörg D. , Waterboer Tim , Butt Julia , Aragonés Nuria , Hufnagel Katrin
Published: September 2020

Background:

Helicobacter pylori (H. pylori) is a bacterial carcinogen and the leading risk factor for noncardia gastric cancer (NCGC). Detecting antibodies against specific H. pylori proteins in peripheral blood can be applied to characterize infection and determine disease associations. Most studies analyzing the association between H. pylori infection and gastric cancer have focused on previously identified antigens, predominantly the virulence factor cytotoxin-associated gene A (CagA). Selecting antigens in an unbiased approach may, however, allow the identification of novel biomarkers.

Methods:

Using a combination of multiple spotting technique and cell-free, on-chip protein expression, we displayed the H. pylori genome (strain 26695) on high-density microarrays. Immunogenic proteins were identified by serum pool incubations and henceforth analyzed in individual samples. To test its applicability, we used sera from a multicase–control (MCC)-Spain study. Serologic responses between NCGC cases and controls were assessed by conditional logistic regression estimating ORs and 95% confidence intervals.

Results:

We successfully expressed 93% of the 1,440 H. pylori open reading frames in situ. Of these, 231 (17%) were found to be immunogenic. By comparing 58 NCGC cases with 58 matched controls, we confirmed a higher seroprevalence of CagA among cases (66%) than controls (31%). We further identified a potential novel marker, the Helicobacter outer membrane protein A (HopA).

Conclusions:

In this study, we provide evidence that our H. pylori whole-proteome microarray offers a platform for unbiased de novo identification of serologic biomarkers.

Impact:

Given its versatile workflow, antibody responses against other H. pylori strains and possible associations with diverse H. pylori–related outcomes can be systematically analyzed.
The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids
Authors: Houghton Lauren C. , Howland Renata E. , Wei Ying , Ma Xinran , Kehm Rebecca D. , Chung Wendy K. , Genkinger Jeanine M. , Santella Regina M. , Hartmann Michaela F. , Wudy Stefan A. , Terry Mary Beth
Published: September 2020

Background:

No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk.

Methods:

We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case–control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels.

Results:

The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3–5.3) and androgens (aOR = 1.6; 95% CI = 1.0–2.7) was associated with increased breast cancer risk. Specific glucocorticoids (THE, THF αTHF, 6β-OH-F, THA, and α-THB) were associated with 49% to 161% increased risk. Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1–2.7) and 90% (aOR = 1.9; 95% CI = 1.2–3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0–2.7) increased risk. E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively.

Conclusions:

Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum.

Impact:

If replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.
Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia
Authors: Zeidner Joshua F. , Lee Daniel J. , Frattini Mark , Fine Gil D. , Costas Judy , Kolibaba Kathryn , Anthony Stephen P. , Bearss David , Smith B. Douglas
Published: September 2020

Purpose:

Alvocidib is a cyclin-dependent kinase 9 inhibitor leading to downregulation of the antiapoptotic BCL-2 family member, MCL-1. Alvocidib has shown clinical activity in a timed sequential regimen with cytarabine and mitoxantrone in relapsed/refractory and newly diagnosed acute myeloid leukemia (AML) but has not been studied in combination with traditional 7+3 induction therapy.

Patients and Methods:

A multiinstitutional phase I dose-escalation study of alvocidib on days 1–3 followed by 7+3 (cytarabine 100 mg/m2/day i.v. infusion days 5–12 and daunorubicin 60 mg/m2 i.v. days 5–7) was performed in newly diagnosed AML ≤65 years. Core-binding factor AML was excluded.

Results:

There was no MTD on this study; the recommended phase II dose of alvocidib was 30 mg/m2 i.v. over 30 minutes followed by 60 mg/m2 i.v. infusion over 4 hours. There was one dose-limiting toxicity of cytokine release syndrome. The most common grade ≥3 nonhematologic toxicities were diarrhea (44%) and tumor lysis syndrome (34%). Overall, 69% (22/32) of patients achieved complete remission (CR). In an exploratory cohort, eight of nine (89%) patients in complete remission had no measurable residual disease, as determined by a centralized flow cytometric assay. Clinical activity was seen in patients with secondary AML, AML with myelodysplastic syndrome–related changes, and a genomic signature of secondary AML (50%, 50%, and 92% CR rates, respectively).

Conclusions:

Alvocidib can be safely administered prior to 7+3 induction with encouraging clinical activity. These findings warrant further investigation of alvocidib combinations in newly diagnosed AML. This study was registered at clinicaltrials.gov identifier NCT03298984.
Survival Implications of the Relationship between Tissue versus Circulating Tumor DNA TP53 Mutations—A Perspective from a Real-World Precision Medicine Cohort
Authors: Rosenberg Shai , Okamura Ryosuke , Kato Shumei , Soussi Thierry , Kurzrock Razelle
Published: September 2020

Interrogating the genomics of circulating tumor DNA (ctDNA; the liquid biopsy) has advantages in patients in whom tissue biopsy is difficult. However, the reported concordance between genomic analysis of tissue DNA and ctDNA is variable among studies. Herein, we characterized the clinical implications of the relationship between mutations in TP53 genes in tissue DNA versus ctDNA. The molecular profiles of both liquid (Guardant Health) and tissue (Foundation Medicine) biopsies from 433 patients were analyzed (pan-cancer setting). In 71/433 (16%) cases, all same TP53 mutations were detected in both tissue DNA and ctDNA; in 18/433 (4%), same mutation plus additional mutation/mutations; and in 27/433 (6%), different TP53 mutations were detected. In 99/433 (23%) cases, TP53 mutations were detected only in tissue DNA; in 43/433 (10%), only in ctDNA; and in 175/433 (40%), no TP53 mutations were detected in either test. When TP53 mutations were identical in tissue and ctDNA, the alterations were enriched for nonsense mutations, and survival was significantly shorter in multivariate analysis (as compared with different mutations in ctDNA vs. tissue or no mutations); this finding was independent of tumor type, time interval between tests, and the %ctDNA for TP53 mutations. In summary, in 16% of 433 patients with diverse cancers, TP53 mutations were identical in tissue DNA and ctDNA. In these individuals, the alterations were enriched for stop–gain (nonsense) mutations (results in a premature termination codon). Though unknown confounders cannot be ruled out, these patients fared significantly worse than those whose ctDNA and tissue DNA harbored different TP53 mutation portfolios or no TP53 mutations.
PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study
Authors: Derbyshire Abigail E. , Allen Jennifer L. , Gittins Matthew , Lakhiani Bhavna , Bolton James , Shaw Joseph , Pemberton Philip W. , Needham Michelle , MacKintosh Michelle L. , Edmondson Richard J. , Kitchener Henry C. , Crosbie Emma J.
Published: September 2020

Obesity is the major etiologic driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity [body mass index (BMI) > 40 kg/m2] and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion, and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate, and 25 received a LNG-IUS. Their median age and BMI were 54 years [interquartile range (IQR) 52–57] and 47 kg/m2 (IQR 44–51), respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphologic change, reduced Ki-67, and PR expression, but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.

Prevention Relevance: Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial.
Unilateral Koilonychia Secondary to Chemical Depilatory Product
Authors: Gupta Isha , Tyagi Meha , Dayal Surabhi , Singh Jayanti
Published: September 2020

Excess hair is a problem for both men and women who want to conform to today’s cosmetic social norms. Chemical depilatories are a safe, fast, and inexpensive method of hair removal. The most commonly used depilatory agents are thioglycolates and to a lesser extent, sulphides. The most common side effect of chemical depilatories is irritant contact dermatitis. However, allergic contact dermatitis is rare and may be related to lanolin, fragrance, or thioglycolate itself. Unilateral koilonychia as a side effect of chemical depilatories has not been described previously in the literature. We report this case due to its rarity and highlight the significance of nail protection while using chemical depilatory products.
Reanatomização dental pela técnica direta com guias de silicone
Authors: Detogni Anna Caroliny , Piana Ediana Amanda , Gadonski Ana Paula , Camilotti Veridiana
Published: September 2020

A reanatomização dental tem se tornado um procedimento de elevada relevância no dia a dia odontológico, uma vez que inconformidades com a aparência estética do sorriso estão cada vez mais frequentes. Para sua realização, várias técnicas e materiais estão disponíveis, dentre os quais restaurações cerâmicas, como lentes de contato, facetas e coroas, além das restaurações em resinas compostas. Estas se destacam por sua abordagem minimamente invasiva, proporcionando características ópticas e mecânicas favoráveis à estrutura dental, as quais permitem a reprodução das caraterísticas dos tecidos dentais naturais, tais como translucidez e opacidade, além de garantir longevidade às restaurações. Várias técnicas podem ser empregadas para a realização da reanatomização com a resina composta, dentre as quais podemos destacar a técnica direta, com o uso de guias de silicone. Assim, este trabalho tem como objetivo apresentar um relato de caso clínico realizado na Clínica de Odontologia da Universidade Estadual do Oeste do Paraná, por meio do uso das guias de silicone vestibular e palatina para o restabelecimento estético dos dentes anteriores superiores, visando a ressaltar sua confecção laboratorial, aplicação clínica e as vantagens de seu uso.
Endothelial
BMPR2
Loss Drives a Proliferative Response to BMP (Bone Morphogenetic Protein) 9 via Prolonged Canonical Signaling
Authors: Theilmann Anne L. , Hawke Lindsey G. , Hilton L. Rhiannon , Whitford Mara K.M. , Cole Devon V. , Mackeil Jodi L. , Dunham-Snary Kimberly J. , Mewburn Jeffrey , James Paula D. , Maurice Donald H. , Archer Stephen L. , Ormiston Mark L.
Published: October 2020

Objective:

Pulmonary arterial hypertension is a disease of proliferative vascular occlusion that is strongly linked to mutations in
BMPR2
—the gene encoding the BMPR-II (BMP [bone morphogenetic protein] type II receptor). The endothelial-selective BMPR-II ligand, BMP9, reverses disease in animal models of pulmonary arterial hypertension and suppresses the proliferation of healthy endothelial cells. However, the impact of
BMPR2
loss on the antiproliferative actions of BMP9 has yet to be assessed.

Approach and Results:

BMP9 suppressed proliferation in blood outgrowth endothelial cells from healthy control subjects but increased proliferation in blood outgrowth endothelial cells from pulmonary arterial hypertension patients with
BMPR2
mutations. This shift from growth suppression to enhanced proliferation was recapitulated in control human pulmonary artery endothelial cells following siRNA-mediated
BMPR2
silencing, as well as in mouse pulmonary endothelial cells isolated from endothelial-conditional
Bmpr2
knockout mice (
Bmpr2

EC

−/−
). BMP9-induced proliferation was not attributable to altered metabolic activity or elevated TGFβ (transforming growth factor beta) signaling but was linked to the prolonged induction of the canonical BMP target
ID1
in the context of
BMPR2
loss. In vivo, daily BMP9 administration to neonatal mice impaired both retinal and lung vascular patterning in control mice (
Bmpr2

EC+/+

) but had no measurable effect on mice bearing a heterozygous endothelial
Bmpr2
deletion (
Bmpr2

EC
+/−

) and caused excessive angiogenesis in both vascular beds for
Bmpr2

EC

−/−
mice.

Conclusions:

BMPR2
loss reverses the endothelial response to BMP9, causing enhanced proliferation. This finding has potential implications for the proposed translation of BMP9 as a treatment for pulmonary arterial hypertension and suggests the need for focused patient selection in clinical trials.
Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER‐AMI Study
Authors: Hajduk Alexandra M. , Dodson John A. , Murphy Terrence E. , Tsang Sui , Geda Mary , Ouellet Gregory M. , Gill Thomas M. , Brush John E. , Chaudhry Sarwat I.
Published: October 2020

Background

Functional decline (ie, a decrement in ability to perform everyday activities necessary to live independently) is common after acute myocardial infarction (AMI) and associated with poor long‐term outcomes; yet, we do not have a tool to identify older AMI survivors at risk for this important patient‐centered outcome.

Methods and Results

We used data from the prospective SILVER‐AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction) study of 3041 patients with AMI, aged ≥75 years, recruited from 94 US hospitals. Participants were assessed during hospitalization and at 6 months to collect data on demographics, geriatric impairments, psychosocial factors, and activities of daily living. Clinical variables were abstracted from the medical record. Functional decline was defined as a decrement in ability to independently perform essential activities of daily living (ie, bathing, dressing, transferring, and ambulation) from baseline to 6 months postdischarge. The mean age of the sample was 82±5 years; 57% were men, 90% were White, and 13% reported activity of daily living decline at 6 months postdischarge. The model identified older age, longer hospital stay, mobility impairment during hospitalization, preadmission physical activity, and depression as risk factors for decline. Revascularization during AMI hospitalization and ability to walk a quarter mile before AMI were associated with decreased risk. Model discrimination (c=0.78) and calibration were good.

Conclusions

We identified a parsimonious model that predicts risk of activity of daily living decline among older patients with AMI. This tool may aid in identifying older patients with AMI who may benefit from restorative therapies to optimize function after AMI.
Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: A Systematic Review and Meta‐Analysis of Prospective Cohort Studies
Authors: Zurbau Andreea , Au‐Yeung Fei , Blanco Mejia Sonia , Khan Tauseef A. , Vuksan Vladimir , Jovanovski Elena , Leiter Lawrence A. , Kendall Cyril W. C. , Jenkins David J. A. , Sievenpiper John L.
Published: October 2020

Background

Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta‐analysis of prospective cohort studies.

Methods and Results

MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle‐Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane‐Q and I
2
) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty‐one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89–0.96]; 0.91 [0.88–0.95]; and 0.94 [0.90–0.97], respectively), coronary heart disease (0.88 [0.83–0.92]; 0.88 [0.84–0.92]; and 0.92 [0.87–0.96], respectively), and stroke (0.82 [0.77–0.88], 0.82 [0.79–0.85]; and 0.88 [0.83–0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85–0.93]; 0.88 [0.86–0.91]; and 0.87 [0.85–0.90], respectively), coronary heart disease (0.81 [0.72–0.92]; 0.86 [0.82–0.90]; and 0.86 [0.83–0.89], respectively), and stroke (0.73 [0.65–0.81]; 0.87 [0.84–0.91]; and 0.94 [0.90–0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was “very low” to “moderate,” with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables.

Conclusions

Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT03394339.
Association of Isolated Diastolic Hypertension Based on the Cutoff Value in the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines With Subsequent Cardiovascular Events in the General Population
Authors: Kaneko Hidehiro , Itoh Hidetaka , Yotsumoto Haruki , Kiriyama Hiroyuki , Kamon Tatsuya , Fujiu Katsuhito , Morita Kojiro , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Yasunaga Hideo , Komuro Issei
Published: September 2020

Background

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain.

Methods and Results

We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged <20 years, had systolic hypertension, were taking antihypertensive medication, or had prevalent cardiovascular disease, and studied 1 746 493 individuals (mean age, 42.9±10.7 years; 961 097 men [55.0%]). The average observational period was 1107±855 days. Stage 1 IDH, defined as diastolic BP 80 to 89 mm Hg, and stage 2 IDH, defined as diastolic BP ≥90 mm Hg, were found in 230 513 (13.2%) and 16 159 (0.9%) individuals, respectively. Compared with individuals with normal diastolic BP, individuals with stage 1 and stage 2 IDH were older and more likely to be men. Prevalence of classic risk factors was higher in patients with IDH. Kaplan–Meier curves showed that stage 1 and stage 2 IDH were associated with a higher incidence of cardiovascular events, defined as myocardial infarction, angina pectoris, and stroke. Multivariable analysis showed that stage 1 (hazard ratio [HR], 1.17) and stage 2 (HR, 1.28) IDH were independently associated with a higher incidence of cardiovascular events. Subgroup analyses showed that the association of IDH with cardiovascular events was seen irrespective of age and sex.

Conclusions

The analysis of a nationwide epidemiological database showed that IDH based on the cutoff value in the 2017 ACC/AHA BP guidelines was associated with an elevated risk of subsequent cardiovascular events.
Molecular identification, phylogeny and phylogeography of the entomopathogenic nematodes of the genus Heterorhabditis Poinar, 1976: a multigene approach
Authors: Dhakal Manoj , Nguyen Khuong B. , Hunt David J. , Ehlers Ralf-Udo , Spiridonov Sergei E. , Subbotin Sergei A.
Published: October 2020

Presently, the genus Heterorhabditis contains 16 valid entomopathogenic nematode species. In this study we used samples from 11 species: H. amazonensis, H. bacteriophora, H. baujardi, H. beicherriana, H. downesi, H. floridensis, H. georgiana, H. indica, H. megidis, H. noenieputensis, and H. zealandica to amplify and sequence five gene fragments: the D2-D3 expansion segments of 28S rRNA, ITS rRNA, COI mtDNA genes and unc-87 and cmd-1 genes encoding thin filament (F-actin)-associated protein and calmodulin, respectively. Fifty new sequences for 11 species were generated. More than 980 sequences of five genes were analysed. Phylogenetic and sequence analysis of these genes using Bayesian inference, maximum likelihood and statistical parsimony confirmed a division of the genus into three clades (groups): ‘Indica’, ‘Bacteriophora’ and ‘Megidis’. The analysis of gene sequences downloaded from GenBank and identified as Heterorhabditis revealed many cases of species misidentifications and presence of reading mistakes in some sequences. Synonymisation of H. somsookae with H. baujardi, H. gerrardi, H. pakistanensis with H. indica, and H. sonorensis with H. taysearae, are confirmed by sequence and phylogenetic analysis. The ITS rRNA and COI genes could be considered as informative markers for species identification, barcoding and phylogeographical studies of Heterorhabditis.
Knema flavostamina (Myristicaceae), a new species from southern Western Ghats, India

Authors: GOVIND MURUGAN GOVINDAKURUP , DAN MATHEW
Published: September 2020

Myristicaceae Brown (1810: 399), the pantropical ‘nutmeg family’, comprise 21 genera and 520 species (Christenhusz & Byng 2016). The family thrives in the dense evergreen forests of the Western Ghats and is represented by three genera, viz. Gymnacranthera (Candolle 1855: 31) Warburg (1896: 94), Knema Loureiro (1790: 604) and Myristica Gronovius (1755: 141) (Nayar et al. 2014). Knema, one of the major genera of Myristicaceae with 93 species, is distributed in Indomalaya (Mabberley 2018). In India, the genus is represented by eight species, of which the endemic Knema attenuata (Wallich in Hooker & Thomson, 1855: 157) Warburg (1896: 590) is the only species in the Western Ghats (Sinclair 1961, Nayar et al. 2014, Banik & Bora 2016).
Two new species of idoteid isopods (Crustacea, Isopoda, Idoteidae) from Korea
Authors: KIM SUNG HOON , JUNG TAE WON , YOON SEONG MYEONG
Published: September 2020

Two new species, Cleantiella ampliscutula sp. nov. and Pentias pluriarticulatus sp. nov., are reported from Korean waters with keys to all known species of the genera Cleantiella and Pentias. Cleantiella ampliscutula sp. nov. can be distinguished from its congeners by the following characteristics: the body is relatively small; pereonite 1 is expanded anterolaterally; coxal plates 2–7 are triangular; the pleon has three partial sutures; the pleotelson is widening posteriorly on the lateral margin; the flagellum of the antenna is single-articled; and the maxillipedal palps are four-articled. Pentias pluriarticulatus sp. nov. can be distinguishable from its congeners by the following characteristics: the lateral margins of the body are parallel; the anterior margin of the cephalon is slightly concave and has a small median notch; the coxal plates are invisible dorsally on pereonites 2–4, but visible on pereonites 5–7; the pleon has three partial sutures; the flagellum of the antenna is composed of nine articles; and the distal ends of the uropodal endopods are sinuous.
Description of female genitalia, additional morphological variations, and courtship behavior and copulation of Macrostemum brasiliense (Fischer 1970) (Trichoptera: Hydropsychidae)
Authors: SILVA LARISSA MOREIRA , PAPROCKI HENRIQUE
Published: October 2020

Macrostemum Kolenati 1859 is a cosmopolitan caddisfly genus with 105 described species easily recognized by the remarkable contrasting dark and clear wing patterns. The larvae of the genus build retreats with capture nets adapted to filter fine particulate organic matter. The genus has 19 described, Neotropical species, almost all described only by wing patterns and male genitalia. To date, only two Neotropical species have an associated immature stage and only one has the female genitalia described. Macrostemum brasiliense occurs in southeastern Brazil, primarily in the Atlantic Rainforest. The species has characteristic wing and body patterns, and phallic morphology recorded in literature and further described here. We contribute to knowledge of this species by further describing and illustrating the female genitalia, adding detail about wing variation patterns and venation, including the intriguing melanic female variation. This conspicuous Atlantic Rainforest caddisfly is now among the best-known species of Neotropical Trichoptera.