bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer‐specific survival after radical cystectomy: external validation in a large bi‐institutional cohort
Authors: Muilwijk Tim , Akand Murat , Soria Francesco , Giordano Andrea , Milenkovic Uros , Moris Lisa , Gevaert Thomas , Van Poppel Hendrik , Albersen Maarten , Gontero Paolo , Joniau Steven
Published: July 2020

Objective

To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer‐specific survival (CSS) after radical cystectomy (RC) in a large bi‐institutional cohort of patients.

Patients and Methods

Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan–Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log‐rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C‐indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model.

Results

A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low‐ (0–1) vs intermediate‐ (2–4) vs high‐risk (5–7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C‐indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models.

Conclusion

We performed an external validation of the COBRA score in a large bi‐institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non‐overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.
A hybrid ensemble‐based technique for predicting drug–target interactions
Authors: Sachdev Kanica , Gupta Manoj Kumar
Published: July 2020

Drug–target interaction is the intercommunication between chemical drugs and target proteins to produce any kind of change in the human body. The laboratory experiments conducted to recognize these potential intercommunications are costly and tedious. Various computational methods have been established recently, including the chemogenomic approach for identifying drug–target intercommunication, that integrates the chemical data of the drugs and the genomic properties of the proteins for identifying the interactions between them. This paper proposes a novel technique based on hybrid ensemble to predict drug target interactions. Hybrid ensembles introduce diversity in classification that helps to improve the performance of prediction. The proposed method has been evaluated by comparing the technique with state–of‐the‐art methods on two different databases under three cross‐validation settings. The comparison clearly shows that the technique produced significant improvement in the interaction prediction.
Obesity, menstrual irregularity and polycystic ovary syndrome in young women with type 1 diabetes: A population‐based study
Authors: Thong Eleanor P. , Milat Frances , Joham Anju E. , Mishra Gita D. , Teede Helena
Published: July 2020

Background

Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications.

Objective

To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls.

Methods

Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989‐95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self‐reported menstrual irregularity, PCOS and BMI.

Results

Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m2, P < .001), where over half were overweight or obese (54.4% vs 32.9%, P < .001). Median BMI increased by 1.11 and 0.45 kg/m2, in the T1D and control groups, respectively. T1D was independently associated with an increased risk of menstrual irregularity (RR 1.22, 95% CI 1.02‐1.46) and PCOS (RR 2.41, 95% CI 1.70‐3.42). Obesity conferred a 4‐fold increased risk of PCOS, compared to those with normal BMI (RR 3.93, 95% CI 3.51‐4.42).

Conclusions

Obesity is prevalent amongst women with T1D and may be a key contributor to the higher risk of menstrual irregularity and PCOS in this cohort, representing an important opportunity for prevention and intervention.
Patch testing with purified and oxidized citronellol
Authors: Hagvall Lina , Rudbäck Johanna , Bråred Christensson Johanna , Karlberg Ann‐Therese
Published: July 2020

Background

Citronellol is a commonly used fragrance terpene included in fragrance mix II. As with many other fragrance terpenes, citronellol is susceptible to autoxidation. Citronellol hydroperoxides are formed in large amounts and are the only oxidation products identified as sensitizers in oxidized citronellol.

Aim

To compare frequencies of contact allergy to purified and oxidized citronellol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series, oxidized linalool, and oxidized limonene.

Methods

A total of 658 dermatitis patients were patch tested with purified and oxidized citronellol at 2.0%, 4.0%, 6.0%, and 1.0%, 2.0%, 4.0%, 6.0% petrolatum, respectively. The irritant properties of purified and oxidized citronellol were studied before patch testing.

Results

Few irritant reactions were observed in the pretest. Purified citronellol detected positive reactions in 0.15%–0.31% of patients, while oxidized citronellol detected positive reactions in 0.61%–4.5%. Among patients reacting to oxidized citronellol, 34%–50% showed concomitant reactions to fragrance markers of the baseline series and 75%–91% to oxidized linalool or oxidized limonene.

Conclusion

Oxidized citronellol detects more cases of contact allergy than purified citronellol, and these cases are not all detected using fragrance mix II. Patch testing with oxidized citronellol will add to the tools in the diagnosis of fragrance allergy.
Anal dysplasia as an incidental finding: the importance of specimen evaluation
Authors: Kavalukas S. L. , Yang F. , Wexner S. D. , Nogueras J. J.
Published: July 2020

Aim

The incidence of anal squamous cell carcinoma (SCC) has increased dramatically in the USA. The squamous intraepithelial lesion has been identified as a precursor lesion to SCC, stratifying the abnormality into low grade or high grade. There have been studies on the prevalence of incidentally found SCC in haemorrhoidectomy specimens, but there are no studies to date on the incidence of dysplasia. The purpose of this study was to establish a baseline incidence of dysplasia that provides helpful information for future epidemiological studies.

Methods

This is a retrospective review of patients who underwent haemorrhoidectomy from 2005 to 2019. Pathology regarding the type of dysplasia, medications, and diagnoses that may predispose to immunosuppression were collected.

Results

In all, 810 patients with a mean age of 51.7 (range 20–91) years underwent haemorrhoidectomy. Eighteen (2.2%) of the patients had abnormal pathology (low‐grade squamous intraepithelial lesion, 3; high‐grade squamous intraepithelial lesion, 12; SCC, 2; adenocarcinoma, 1). Thirty‐seven (4.5%) of the entire cohort had some risk factors for immunosuppression: chronic steroid use (nine), human immunodeficiency virus (HIV) (13), biologic medications (six), transplant recipients (two) and immunocompromising diseases (four). Only 4/18 patients had an immunosuppression risk in that all four of these patients were HIV‐positive. Surveillance following excision was undertaken for an average of 6 (range 1–12) months, during which time four patients underwent a repeat biopsy.

Discussion

Anal dysplasia found in an otherwise asymptomatic population has a prevalence of 2.2%. This finding supports the routine examination of benign anorectal specimens undergoing microscopic examination. Interestingly, the majority of the patients identified had no immunosuppressant risk factors.
The visual array task: A novel gaze‐based measure of object label and category knowledge
Authors: Hauschild Kathryn M. , Pomales‐Ramos Anamiguel , Strauss Mark S.
Published: July 2020

Visual attention measures of receptive vocabulary place minimal task demand on participants and produce a more accurate measure of language comprehension than parent report measures. However, current gaze‐based measures employ visual comparisons limited to two simultaneous items. With this limitation, the degree of similarity of the target to the distractor can have a significant impact on the interpretation of task performance. The current study evaluates a novel gaze‐based paradigm that includes an eight‐item array. This visual array task (VAT) combines the theoretical frameworks of the Intermodal Preferential Looking Paradigm (IPLP) and looking‐while‐listening (LWL) methods of language comprehension measurement but using a larger array of simultaneously presented items. The use of a larger array of items and the inclusion of a superordinate category contrast may provide a more sensitive measure of receptive vocabulary as well as an understanding of the extent to which early word comprehension reflects knowledge of broader categories. Results indicated that the tested VAT was a sensitive measure of both object label and category knowledge. This paradigm provides researchers with a flexible and efficient task to measure language comprehension and category knowledge while reducing behavioral demands placed on participants.
Symptomatic cervical spinal stenosis in spastic cerebral palsy
Authors: Hung Chun Wai , Matsumoto Hiroko , Ball Jacob R , Plachta Stephen , Dutkowsky Joseph P , Kim Heakyung , Hyman Joshua E , Riew K Daniel , Roye David P
Published: July 2020

Aim

To describe the prevalence of symptomatic cervical spinal stenosis (CSS) in spastic cerebral palsy (CP) and associated characteristics.

Method

This cross‐sectional study of adults (>18y) with CP (2006–2016) at a single institution compared the patient characteristics (demographics, comorbidities, surgical history, medications, Gross Motor Function Classification System [GMFCS] level, and CP type) of patients with and without CSS.

Results

Of 424 patients (mean age 33y 4mo, SD 13y 6mo, range 18–78y; 225 females, 199 males), 32 patients (7.5%) had symptomatic CSS. GMFCS levels in the study cohort were distributed as follows: level I, 25%; level II, 25%; level III, 22%; level IV, 19%; level V, 9%. Twenty‐five out of 32 (78.1%) patients had spastic CP, two (6.3%) had dystonic CP, and one (3.1%) had mixed characteristics. Individuals with CSS were older (mean age 54y 6mo, SD 10y 5mo vs mean age 31y 7mo, SD 12y 1mo,p<0.05) and had a higher body mass index (26.1, SD 4.8 vs 23.4, SD 6.2,p<0.05) than those without CSS. Presentations included upper‐extremity symptoms (73%), ambulation decline (70%), neck pain (53%), and incontinence (30%). Common stenosis levels were C5–C6 (59%), C4–C5 (56%), and C6–C7 (53%).

Interpretation

Symptomatic CSS was identified in 7.5% of this adult cohort during the 2006 to 2016 period. Diagnosis in CP is difficult due to impaired communication and pre‐existing gait abnormalities and spasticity. Given the high prevalence of symptomatic CSS in adults, we propose developing screening guidelines. Physicians must maintain a high level of suspicion for CSS if patients present with changes in gait or spasticity.
Trial of restarting and tolerating metformin (TreatMet)
Authors: Orloff Jeremy N. , Touhamy Samir H. , Truong Wanda , Casper Anthony , Shukla Alpana P. , Igel Leon I. , Flory James H.
Published: July 2020

This randomized, double‐blind, placebo‐controlled, n‐of‐1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow‐up or were non‐adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.
DOES EARLY ACCESS TO PENSION WEALTH IMPROVE HEALTH?
Authors: Kim Seonghoon , Koh Kanghyock
Published: July 2020

We examine the health impacts of early access to public pension wealth by exploiting a unique policy in Singapore allowing individuals to withdraw a proportion of their pension savings after their 55th birthday. For the identification, we employ a regression discontinuity design by comparing individuals before and after their 55th birthday. To address anticipated and lagged health impacts, we adopt the donut regression discontinuity approach. Using nationally representative monthly panel data, we find that early access to pension wealth improves self‐reported overall health. (JEL I10, H55, D15)
Leptin protects brain from ischemia/reperfusion‐induced infarction by stabilizing the blood–brain barrier to block brain infiltration by the blood‐borne neutrophils
Authors: Hung Wan‐Ting , Wang Chen‐Hsuan , Lin Shih‐Yi , Cheng Shu‐Yun , Liao Li‐Ya , Lu Li‐Yu , Chen Yu‐Ju , Huang Yu‐Zhen , Lin Chi‐Hsin , Hsueh Chi‐Mei
Published: July 2020

The cellular and molecular mechanisms underlying leptin‐mediated brain protection against cerebral ischemia were investigated at the blood–brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 μg/kg, intracisternally) could block the I/R‐increased BBB permeability, activation of matrix metallopeptidase 9 (MMP‐9) and brain infiltration of blood–borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO‐1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin‐inhibited brain infiltration of neutrophils. Leptin‐mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose–oxygen–serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R‐increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO‐1 and VE‐Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood‐borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.
Family resources moderate the relationship between seizure control and health‐related quality of life in children with drug‐resistant epilepsy
Authors: Phillips Natalie L. , Widjaja Elysa , Smith Mary Lou
Published: July 2020

Objective

Pediatric drug‐resistant epilepsy (DRE) is associated with poor health‐related quality of life (HRQOL). Achieving seizure control, however, does not improve HRQOL in all children. This study sought to evaluate whether (1) baseline caregiver and family factors are associated with child HRQOL at 1‐year follow‐up over and above epilepsy characteristics, treatment, and seizure outcome; and (2) baseline family factors moderate the association between seizure outcome and child HRQOL at 1‐year follow‐up.

Methods

This multicenter longitudinal cohort study recruited 152 children with DRE who were being evaluated for surgical candidacy. Child HRQOL was rated by caregivers using the Quality of Life in Childhood Epilepsy Questionnaire at baseline and 1‐year follow‐up. Additional data collected at baseline included child epilepsy characteristics, caregiver demographics, caregiver mood, and family environment.

Results

Seizure freedom was achieved in 68% and 28% of patients 1 year after surgery and medical treatment, respectively. Caregiver and family factors were not associated with higher child HRQOL at follow‐up after accounting for epilepsy characteristics, treatment, seizure outcome, and baseline child HRQOL, F11, 131 = 1.34, P = .21, ΔR2 = .04. Family resources moderated the association between seizure outcome and child HRQOL at follow‐up (b = .41, 95% confidence interval [CI] = 0.09‐0.74, P = .03); seizure freedom was strongly associated with higher HRQOL when family resources were high (b = 13.50, 95% CI = 8.35‐18.54, P < .001), relative to when family resources were low (b = 5.17, 95% CI = −0.18 to 10.52, P = .06). Family relationships and demands did not moderate the relationship between seizure outcome and HRQOL.

Significance

Achieving seizure freedom was associated with better HRQOL in children with DRE, but this association was reduced for those children who presented with limited family resources. These results highlight the importance of assessing the family environment during presurgical evaluation and implementing early family‐based intervention and supports to promote better outcomes for children in the long term.
Pest risk analysis of rice root‐knot nematode (Meloidogyne graminicola) for the Italian territory
Authors: Torrini G. , Roversi P. F. , Cesaroni C. F. , Marianelli L.
Published: July 2020

Meloidogyne graminicola is one of the most harmful organisms associated with rice cultivation throughout the world. Until recently, M. graminicola was present only in Asia, parts of the Americas, Madagascar and South Africa. In 2016, it was detected for the first time in mainland Europe (Northern Italy) and subsequently added to the EPPO Alert List. In this study, the risk posed by this nematode to rice in Italy was assessed using an internationally developed pest risk analysis scheme. In the risk assessment section, information about biology, pathways for entry, the likelihood of establishment, spread and negative impact of
M. graminicola are reviewed. Internationally, its spread is more likely through the movement of infested host plants, soil or growing medium and non‐host plant parts that may have growing medium attached, from areas where this nematode occurs. Migrant waterbirds, machinery and travellers were also considered as possible pathways for entry. The probability of establishment is very likely due to the suitable environmental conditions and the large range of host plant species present in Italy. This and the nematodes’ ability to survive for long periods in low oxygen environments make the control of
M. graminicola very difficult.
Long‐term exposure to increasing temperature can offset predicted losses in marine food quality (fatty acids) caused by ocean warming
Authors: Jin Peng , Gonzàlez Gala , Agustí Susana
Published: July 2020

Marine phytoplankton produce essential fatty acids (FA), which are key component of a healthy diet in humans and marine food webs. Increased temperatures can reduce lipid and FA content in phytoplankton; thus, ocean warming poses a risk for the global production of these essential FA. However, responses to warming may differ between phytoplankton species especially after long‐term exposure because phenotypic plasticity, de novo mutations, or genetic evolution may occur. Here, we examine the content of FA and lipids in phytoplankton following long‐term selection (~2 years) to warming conditions (+4°C), and we observe that FA and lipids content were partly or entirely recovered following long‐term exposure to warming conditions. Furthermore, this observed long‐term response also offset the predicted losses of some essential polyunsaturated fatty acids (PUFA) in three of the four species tested. Our study suggests that long‐term exposure of phytoplankton to warming may help to maintain marine food quality in a moderately warming ocean. The responses of FA to increasing temperatures may vary among species, and the level of this idiosyncrasy remains to be further studied.
The secondary‐structured DNA‐binding activity of Dna2 endonuclease/helicase is critical to cell growth under replication stress
Authors: Park Soyeong , Karatayeva Nargis , Demin Annie Albert , Munashingha Palinda Ruvan , Seo Yeon‐Soo
Published: July 2020

Dna2 can efficiently process 5′ flaps containing DNA secondary structure using coordinated action of the three biochemical activities: the N‐terminally encoded DNA‐binding activity and the C‐terminally encoded endonuclease and helicase activities. In this study, we investigated the cross talk among the three functional domains using a variety of dna2 mutant alleles and enzymes derived thereof. We found that disruption of the catalytic activities of Dna2 activated Dna2‐dependent checkpoint, residing in the N‐terminal domain. This checkpoint activity contributed to growth defects of dna2 catalytic mutants, revealing the presence of an intramolecular functional cross talk in Dna2. The N‐terminal domain of Dna2 bound specifically to substrates that mimic DNA replication fork intermediates, including Holliday junctions. Using site‐directed mutagenesis of the N‐terminal domain of Dna2, we discovered that five consecutive basic amino acid residues were essential for the ability of Dna2 to bind hairpin DNA in vitro. Mutant cells expressing the dna2 allele containing all five basic residues substituted with alanine displayed three distinct phenotypes: (i) temperature‐sensitive growth defects, (ii) bypass of S‐phase arrest, and (iii) increased sensitivity to DNA‐damaging agents. Taken together, our results indicate that the interplay between the N‐terminal regulatory and C‐terminal catalytic domains of Dna2 plays an important role in vivo, especially when cells are placed under replication stress.
Effects of scanning speed on creep behaviour of 316L stainless steel produced using selective laser melting
Authors: Yu Jong Min , Dao Van Hung , Yoon Kee Bong
Published: July 2020

Increasing numbers of critical components for the aerospace and power industries are fabricated using additive manufacturing (AM). To increase the productivity of high‐temperature components by AM, the scanning speed needs to be maximized without sacrificing the required creep properties. In this study, five rectangular blocks were manufactured using selective laser melting while varying the scanning speed from 420 to 980 mm/s. Small punch creep tests were conducted at 650°C using 10 × 10 × 0.5 mm specimens machined from each block. Creep deformation and rupture life were measured. Power law creep constants were also determined. Difference of creep behaviours were explained based on the microstructures showing pore defects and the measured metal density values. A 3D response surface plot was employed to predict the creep life as a function of the scanning speed and the energy density. As a consequence, a scanning speed range of 416 to 572 mm/s is recommended to maximize productivity and to increase creep resistance.
Online Flow‐Based Spectrophotometric Determination of Ferrous Iron Mass Fraction and Total Iron Mass Fraction in Twenty‐Seven Rock Reference Materials Using a Schlenk line Technique
Authors: Xue Ding‐Shuai , Su Ben‐Xun , Liu Yan‐Hong , Zhang Dan‐Ping , Guo Qian , Guo Ju‐Jie , Sun Jie‐Fang , Sakyi Patrick Asamoah
Published: July 2020

We developed an online continuous‐flow spectrophotometric method for determination of ferrous iron and total iron mass fractions in various types of geological certified reference materials (CRMs) using a Schlenk line technique to exclude oxygen during the digestion process. The continuous‐flow technique enabled automatic, reliable and real‐time analysis, and decreased sample and reagent consumption. The Schlenk line expels air to prevent oxidation during sample digestion. Compared with traditional spectrophotometric procedures, this analytical procedure is easier, more automated and more accurate. The composition of the acid matrix and time used to dissolve the samples were carefully examined. The procedure was tested on 186 replicates of twenty‐seven rock CRMs, and the results showed good agreement with the compiled values from the literature. Based on the statistical data, the proposed procedure was found to be accurate within 0.12% m/m for ferrous iron mass fraction and 0.084% m/m for total iron mass fraction compared with the certified/recommended values. The proposed procedure is accurate, reproducible and has a high throughput (ten samples per hour).
Use of glass polishing waste in the development of ecological ceramic roof tiles by the geopolymerization process
Authors: de Azevedo Afonso R. G. , Marvila Markssuel Teixeira , Rocha Higor Azevêdo , Cruz Lucas Reis , Vieira Carlos Mauricio Fontes
Published: July 2020

The production process of ceramic roof tiles requires a large consumption of natural raw material, such as clay, and energy consumption in the sintering process. Thus, the objective of this research was the development of more ecological tile for civil construction, adopting the process of geopolymerization, which does not require burning, and the use of glass polishing waste, in partial replacement of natural raw material. Prismatic specimens were made with a ratio of alkaline solution/ (metakaolin + waste) = 0.26 and variation of the curing time in 7, 28, and 60 days, and a ratio of precursors with SiO2/Al2O3 varying in 2.5, 3.0, 3.5, and 4.0 for the evaluation of technological properties such as apparent specific mass, linear shrinkage, water absorption, and mechanical resistance to flexion, in addition to microstructural evaluations and the physical, chemical, and mineralogical characterization of the waste. The results showed that the glass waste had potential for use as a precursor in the geopolymerization process, and that the specimens with a 7 days cure and a SiO2/Al2O3 = 4 ratio are the most recommended for the production of roof tiles for civil construction.
Scabies coexisting with other dermatoses: the importance of recognizing multiple pathologies in resource‐poor settings
Authors: Padovese Valeska , Dassoni Federica , Morrone Aldo
Published: July 2020

Background

Background Skin Neglected Tropical Diseases (NTDs) are a group of ten diseases often co‐endemic in African rural communities and characterized by primary skin involvement. If not diagnosed and treated promptly, they can lead to long‐term disfigurement, disability, stigmatization, and socioeconomic loss. Scabies is a parasitic disease and it was added in 2017 to the World Health Organization's (WHO) list of NTDs. Skin NTDs comorbidities differ according to the local diseases burden and are associated to other poverty‐related illnesses.

Methods

We report a case series of scabies and comorbidities in children from rural Ethiopia aimed at highlighting diagnostic challenges.

Results

We propose an epidemiological framework to the integrated skin NTDs approach at a community level.

Conclusion

This bottleneck approach may significantly reduce skin diseases burden in rural communities, prevent long‐term disabilities, and contain costs.
Molecular and clinical profile of congenital fibrinogen disorders in Iran, identification of two novel mutations
Authors: Tavasoli Behnaz , Safa Majid , Dorgalaleh Akbar , Ghasemi Jahan B. , Rezaei Makhouri Farahnaz , Rezvani Mohammad R. , Ahmadi Abbas , Tabibian Shadi , Jazebi Mohammad , Baghaipour Mohammad R. , Zaker Farhad
Published: July 2020

Introduction

Congenital fibrinogen disorders (CFDs) comprise the quantitative and qualitative fibrinogen molecule abnormalities that are caused by fibrinogen gene mutations. The objective of this cohort research was to study the molecular and clinical profiles of patients with CFDs.

Materials and methods

Genomic DNA Sanger sequencing of 14 Iranian patients was performed to determine CFDs‐causing mutations. The disorders were diagnosed by routine and specific (fibrinogen antigen and functional assay) coagulation tests, and clinical data were obtained from medical records. Molecular dynamics (MD) simulations were performed to investigate the effect of missense mutation on the protein structure.

Results

Thirteen out of 14 patients had afibrinogenemia while the remaining patient had dysfibrinogenemia. Umbilical cord bleeding was the most common clinical presentation (n: 9, ~70%) which led to the diagnosis of afibrinogenemia, while menorrhagia led to the diagnosis of dysfibrinogenemia. Six homozygous mutations were identified in afibrinogenemia: three previously described variants in FGA (p.Trp52Ter, p.Ser312AlafsTer109 and p.Gly316GlufsTer105), one in FBG (p.Gly430Asp), and two novel mutations in FGB (p.Gly430Arg) and FGG (p.His366ThrfsTer40), while the FGA (p.Arg38Thr) heterozygous mutation was identified in dysfibrinogenemia. MD simulation indicated that the FGA p. Arg38Thr mutation probably interferes with polymerization of fibrin monomers.

Conclusions

In Iran, with its high rate of consanguinity, autosomal recessive afibrinogenemia with severe clinical presentations is relatively common due to heterogeneous molecular defects.
Use of Sysmex XN‐10 red blood cell parameters for screening of hereditary red blood cell diseases and iron deficiency anaemia
Authors: Nivaggioni Vanessa , Bouriche Lakhdar , Coito Sylvie , Le Floch Anne‐Sophie , Ibrahim‐Kosta Manal , Leonnet Caroline , Arnoux Isabelle , Loosveld Marie
Published: July 2020

Introduction

In daily practice in haematology laboratories, red blood cell (RBC) abnormalities are frequent and their management is a real challenge. The aim of this study is to establish a “decision tree” using RBC and reticulocyte parameters from the SYSMEX XN‐10 analyser to distinguish between patients with a hereditary RBC disease from iron deficiency anaemia and other patients.

Methods

We analysed results of complete RBC counts in a cohort composed of 8217 adults divided into 5 different groups: iron deficiency anaemia (n = 120), heterozygous haemoglobinopathy (n = 92), sickle cell disease syndrome (n = 56), hereditary spherocytosis (n = 18) and other patients (n = 7931). A Classification And Regression Tree (CART) analysis was used to obtain a two‐step decision tree in order to predict these previous groups.

Results

Five parameters and the calculated RBC score were selected by the CART method: mean corpuscular haemoglobin concentration, percentage of microcytes, distribution width of the RBC histogram, percentage of nucleated red blood cells, immature reticulocytes fraction and finally RBC Score. When applying the tree and recommended flowchart, 158/166 of the RBC hereditary disease patients and 114/120 iron deficiency anaemia patients are detected. Overall, the correct classification rate reached 99.4%. Sensitivity and specificity for RBC disease detection were 95.2% and 99.9%, respectively. These results were confirmed in an independent validation cohort.

Conclusion

Based on the XN‐10 RBC and reticulocyte parameters, we propose a two‐step decision tree delivering a good prediction and classification of hereditary RBC diseases. These results can be used to optimize additional reticulocyte analysis and microscopy review.
Molecular characteristics and markers of advanced clear cell renal cell carcinoma: Pitfalls due to intratumoral heterogeneity and identification of genetic alterations associated with metastasis
Authors: Obeng Rebecca C , Arnold Rebecca S , Ogan Kenneth , Master Viraj A , Pattaras John G , Petros John A , Osunkoya Adeboye O
Published: July 2020

Objectives

To identify clear cell renal cell carcinoma‐related gene mutations potentially associated with aggressive disease, sarcomatoid differentiation or poor prognosis.

Methods

We carried out genomic analysis of 217 tumor foci from 25 patients with conventional clear cell renal cell carcinoma (14 patients), clear cell renal cell carcinoma with sarcomatoid differentiation (six patients) and non‐clear cell renal cell carcinoma (five patients). Each tumor nodule on the tissue block that corresponded to the same focus on the slide was separated from the normal parenchyma and other histologically distinct areas of tumor. The isolated tumor foci were used for subsequent analyses and sequencing. Deoxyribonucleic acid from the formalin‐fixed paraffin‐embedded tissues was extracted. Multiplex bar‐coded polymerase chain reaction amplification was carried out using next‐generation sequencing libraries.

Results

Overall, 67 protein alterations, including amino acid alterations, frame shifts and splice site mutations in seven genes were identified in the cohort of renal cell carcinoma tumors included in this study. Fewer patients with clear cell renal cell carcinoma with sarcomatoid differentiation had clear cell renal cell carcinoma‐related mutations in comparison with patients with conventional clear cell renal cell carcinoma. Additionally, the average number of unique clear cell renal cell carcinoma‐related protein alterations per patient was significantly lower in clear cell renal cell carcinoma with sarcomatoid differentiation than in conventional clear cell renal cell carcinoma. Mutations in PBRM1 were identified in a higher proportion of patients with high‐grade tumors (World Health Organization/International Society of Urological Pathology grade 4) and in the primary tumors of six of 10 (60%) patients with metastatic disease.

Conclusions

Although there are pitfalls due to intratumoral heterogeneity and sampling bias, mutations in PBRM1 may be associated with metastasis and aggressive disease in clear cell renal cell carcinoma.
Fibroplasty (venoplasty) to facilitate transvenous lead placement: A single‐center experience
Authors: Kella Danesh K. , Isath Ameesh , Yasin Omar , Padmanabhan Deepak , Webster Tracy , Mulpuru Siva , Cha Yong‐Mei , Friedman Paul A.
Published: July 2020

Introduction

Venous stenosis is a well‐recognized complication of transvenous leads (TVLs) that is encountered during lead revisions or device upgrades. We here report the outcomes of TVL placement facilitated by fibroplasty or tunneling (TUN) procedure.

Methods

We conducted a single‐center retrospective cohort study of all patients undergoing TVL implantation requiring fibroplasty or TUN from 2005 to 2017. Medical records and procedure reports were reviewed for relevant data. Outcomes for fibroplasty and TUN to facilitate TVL placement were compared.

Results

Sixty patients had fibroplasty and thirty‐five patients had a TUN procedure. There was no difference in procedure success rates between the two groups (97% fibroplasty vs. 100% TUN; p = .98). The fluoroscopy time was longer (fibroplasty = 39.7 ± 21.5 min vs. TUN = 29.2 ± 21.3 min; p = .01) and the total procedural time was shorter in the fibroplasty group (fibroplasty = 247 ± 77.8 min vs. TUN = 287 ± 77.1 min; p = .01). TUN was associated with a significantly higher incidence of acute complications (fibroplasty = 0 vs. TUN = 8; p = .002) most requiring invasive intervention and/or transfusion with blood products. Long‐term complications requiring additional device‐related procedures were comparable between the two groups (fibroplasty = 6 vs. TUN = 6; logrank p = .21).

Conclusions

For patients with venous stenosis requiring additional TVL, balloon fibroplasty is associated with similar rates of success and a significantly decreased incidence of acute complications when compared with subcutaneous TUN.
Modified Cornell electrocardiographic criteria in the assessment of left ventricular hypertrophy geometry of patients with essential hypertension
Authors: Xu Min , Ge Zhixiang , Huang Jun , Shao Xiaoliang , Li Jumei , MRCP  , Yang Junhua
Published: July 2020

To evaluate the value of modified Cornell electrocardiographic criteria in the assessment of left ventricular hypertrophy (LVH) for patients with essential hypertension. A total of 381 patients with essential hypertension diagnosed in our hospital were selected. Using the left ventricle (LV) geometric patterns classified by the American Society of Echocardiography (ASE), we examined the distribution of the modified Cornell criteria of Ravl + SD (the deepest S wave in 12‐lead ECG) in different geometric patterns and analyzed the correlation of modified Cornell criteria with changes in the LV geometric patterns using multiple linear regression analysis. The distribution of modified Cornell criteria, Sokolow‐Lyon criteria (RV5/V6 + SV1), and Cornell criteria (Ravl + SV3) in gender‐specific hypertensive geometric patterns were significantly different (P ≤ .01 for all). The voltage of Ravl + SD in male patients showed an increase trend in the normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups, and this increase trend was significantly in the unadjusted model and the adjusted model. The voltages of Ravl + SV3 and RV5/V6 + SV1 of male patients in CR, CH and RH groups showed a gradual increase trend, but the increase trend in CR group has no statistical significance compared to that in NG group (P ≥ .05). The voltages of Ravl + SD, RV5/V6 + SV1, and Ravl + SV3 in female patients in CR, CH and EH groups showed a trend of increase after decrease in the adjusted model. In conclusion, the modified Cornell criteria could dynamically reflect left ventricular hypertensive geometry of male patients.
High neuropilin and tolloid‐like 1 expression associated with metastasis and poor survival in epithelial ovarian cancer via regulation of actin cytoskeleton
Authors: Xu Yunzhao , Wang Wei , Chen Jinling , Mao Haixia , Liu Yuanlin , Gu Shuting , Liu Qinqin , Xi Qinghua , Shi Wenyu
Published: July 2020

Abnormal expression of neuropilin and tolloid‐like 1 (NETO1) has been detected in some human carcinomas. However, the expression of NETO1 and the underlying mechanism in epithelial ovarian cancer (EOC) remain unknown. In this study, we found that a higher NETO1 expression in EOC tissue samples compared to normal ovarian tissue samples was significantly correlated with worse overall survival. Additionally, Cox regression analysis suggested that NETO 1 was independently associated with overall survival. NETO1 overexpression enhanced the EOC cells’ migration and invasion capability in vitro via regulation of actin cytoskeleton. Mechanistically, silencing NETO1 reduced the expression of β‐tubulin, F‐actin and KIF2A. In conclusion, our results demonstrated the critical role of NETO1 in EOC invasion, and therapies aimed at inhibiting its expression or activity might significantly control EOC growth, invasion and metastatic dissemination.
Tuning into the real effect of smartphone use on parenting: a multiverse analysis
Authors: Modecki Kathryn L. , Low‐Choy Samantha , Uink Bep N. , Vernon Lynette , Correia Helen , Andrews Kylie
Published: July 2020

Background

Concerns have been raised regarding the potential negative impacts of parents’ smartphone use on the parent–child relationship. A scoping literature review indicated inconsistent effects, arguably attributable to different conceptualizations of parent phone use and conflation of phone use with technological interference.

Methods

Based on a sample of n = 3, 659 parents collected in partnership with a national public broadcaster, we conducted a multiverse analysis. We explored 84 different analytic choices to address whether associations were weak versus robust, and provide clearer direction for measurement, theory, and practice. Effects were assessed in relation to p values, effect sizes, and AIC; we further conducted a meta‐analytic sensitivity check.

Results

Direct associations between smartphone use and parenting were relatively weak and mixed. Instead, the relation between use and parenting depended on level of technological interference. This pattern was particularly robust for family displacement. At low levels of displacing time with family using technology, more smartphone use was associated with better (not worse) parenting.

Conclusions

Our results indicate fragility in findings of risks for parental smartphone use on parenting; there were few concerns in this regard. Rather, at low levels of technological interference, more phone use was associated with higher parenting quality. Scholars should avoid generalized narratives of family risk and seek to uncover real effects of smartphone use on family outcomes across diverse households and contexts.
Ablative fractional CO2 laser vs lyophilized growth factor intralesional injection vs combination of both modalities for striae distensae treatment
Authors: Abdallah Mahmoud , Fahmy Hossam , Abdel Hameed Shawkat , Mostafa Azza E.
Published: July 2020

Background

Different studies had evaluated the efficacy of fractional CO2 laser and platelet‐rich plasma (PRP) in treating striae distensae (SD). Lyophilized growth factors (LGF) represent another form of delivering growth factors similar to PRP with a more standardized method. To the best of our knowledge, no previous trials have been reported using LGF in SD.

Aims

We aimed to compare the efficacy of ablative fractional CO2 laser vs intralesional injection of LGF vs combination of both modalities for SD treatment.

Methods

This study included 20 female patients with SD. All patients received three modalities of treatment in separate three areas: area A: received fractional CO2 laser, area B: received combination of fractional CO2 laser and intradermal injection of LGF, and area C: received intradermal injection of LGF. Each area received three sessions with 6‐week intervals. The outcome was evaluated clinically and histopathologically before treatment and six weeks after the last session.

Results

There was a statistically significant clinical and histopathological improvement of SD both in areas A and B after treatment. Area C exhibited nonsignificant clinical and histopathological improvement. Area B showed the best improvement results as compared to areas A and C.

Conclusion

We reported that fractional CO2 laser combined with LGF injection was more effective than fractional CO2 laser alone in SD treatment based on clinical and histopathological assessment. We do not advocate LGF as a monotherapy for SD treatment; instead, LGF can be used as a combined therapy with fractional CO2 laser to improve its outcome.
A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study
Authors: Van Olden C. C. , Van de Laar A. W. , Meijnikman A. S. , Aydin O. , Van Olst N. , Hoozemans J. B. , De Brauw L. M. , Bruin S. C. , Acherman Y. I. Z. , Verheij J. , Pyykkö J. E. , Hagedoorn M. , Sanderman R. , Bosma N. C. , Tremaroli V. , Lundqvist A. , Olofsson L. E. , Herrema H. , Lappa D. , Hjorth S. , Nielsen J. , Schwartz T. , Groen A. K. , Nieuwdorp M. , Bäckhed F. , Gerdes V. E. A.
Published: July 2020

Introduction

Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non‐alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood‐samples.

Methods

The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux‐en‐Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal‐samples and intra‐operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra‐operative portal vein blood‐sampling. Fecal‐samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma‐samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq‐analyses. Data will be integrated using state‐of‐the‐art neuronal networks and metabolic modeling. Patient follow‐up will be ten years.

Results

Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra‐individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference.

Conclusion

The BARIA study can add more understanding in how gut‐microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity‐associated disease epidemic.