bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative analysis of differentially expressed proteins in psoriasis vulgaris using tandem mass tags and parallel reaction monitoring
Authors: Li Yu , Lin Peng , Wang Siyao , Li Shuang , Wang Rui , Yang Lin , Wang Hongmei
Published: August 2020

Background

Psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.

Methods

The study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography–mass spectrometry (LC–MS)/MS.

Results

A total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV.

Conclusions

These findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.
UvAtg8-Mediated Autophagy Regulates Fungal Growth, Stress Responses, Conidiation, and Pathogenesis in Ustilaginoidea virens
Authors: Meng Shuai , Xiong Meng , Jagernath Jane Sadhna , Wang Congcong , Qiu Jiehua , Shi Huanbin , Kou Yanjun
Published: August 2020

Background

Ustilaginoidea virens has become one of the most devastating rice pathogens in China, as well as other rice-growing areas. Autophagy is an important process in normal cell differentiation and development among various organisms. To date, there has been no optimized experimental system introduced for the study of autophagy in U. virens. In addition, the function of autophagy in pathogenesis remains unknown in U. virens. Therefore, the functional analyses of UvAtg8 may potentially shed some light on the regulatory mechanism and function of autophagy in U. virens.

Results

In this study, we characterized the functions of UvAtg8, which is a homolog of Saccharomyces cerevisiae ScAtg8, in the rice false smut fungus U. virens. The results showed that UvATG8 is essential for autophagy in U. virens. Also, the GFP-UvATG8 strain, which could serve as an appropriate marker for monitoring autophagy in U. virens, was generated. Furthermore, this study found that the ΔUvatg8 mutant was defective in the vegetative growth, conidiation, adaption to oxidative, hyperosmotic, cell wall stresses, and production of toxic compounds. Pathogenicity assays indicated that deletion of UvATG8 resulted in significant reduction in virulence of U. virens. Further microscopic examinations of the infection processes revealed that the severe virulence defects in the ∆Uvatg8 were mainly caused by the highly reduced conidiation and secondary spore formation.

Conclusions

Our results indicated that the UvAtg8 is necessary for the fungal growth, stresses responses, conidiation, secondary spore formation, and pathogenicity of U. virens. Moreover, our research finding will potentially assist in further clarifying the molecular mechanism of U. virens infection, as well as provide a good marker for autophagy in U. virens and a good reference value for the further development of effective fungicides based on gene targeting.
NPF:network propagation for protein function prediction
Authors: Zhao Bihai , Zhang Zhihong , Jiang Meiping , Hu Sai , Luo Yingchun , Wang Lei
Published: August 2020

Background

The accurate annotation of protein functions is of great significance in elucidating the phenomena of life, treating disease and developing new medicines. Various methods have been developed to facilitate the prediction of these functions by combining protein interaction networks (PINs) with multi-omics data. However, it is still challenging to make full use of multiple biological to improve the performance of functions annotation.

Results

We presented NPF (Network Propagation for Functions prediction), an integrative protein function predicting framework assisted by network propagation and functional module detection, for discovering interacting partners with similar functions to target proteins. NPF leverages knowledge of the protein interaction network architecture and multi-omics data, such as domain annotation and protein complex information, to augment protein-protein functional similarity in a propagation manner. We have verified the great potential of NPF for accurately inferring protein functions. According to the comprehensive evaluation of NPF, it delivered a better performance than other competing methods in terms of leave-one-out cross-validation and ten-fold cross validation.

Conclusions

We demonstrated that network propagation, together with multi-omics data, can both discover more partners with similar function, and is unconstricted by the “small-world” feature of protein interaction networks. We conclude that the performance of function prediction depends greatly on whether we can extract and exploit proper functional information of similarity from protein correlations.
Game theoretic centrality: a novel approach to prioritize disease candidate genes by combining biological networks with the Shapley value
Authors: Sun Min Woo , Moretti Stefano , Paskov Kelley M. , Stockham Nate T. , Varma Maya , Chrisman Brianna S. , Washington Peter Y. , Jung Jae-Yoon , Wall Dennis P.
Published: August 2020

Background

Complex human health conditions with etiological heterogeneity like Autism Spectrum Disorder (ASD) often pose a challenge for traditional genome-wide association study approaches in defining a clear genotype to phenotype model. Coalitional game theory (CGT) is an exciting method that can consider the combinatorial effect of groups of variants working in concert to produce a phenotype. CGT has been applied to associate likely-gene-disrupting variants encoded from whole genome sequence data to ASD; however, this previous approach cannot take into account for prior biological knowledge. Here we extend CGT to incorporate a priori knowledge from biological networks through a game theoretic centrality measure based on Shapley value to rank genes by their relevance–the individual gene’s synergistic influence in a gene-to-gene interaction network. Game theoretic centrality extends the notion of Shapley value to the evaluation of a gene’s contribution to the overall connectivity of its corresponding node in a biological network.

Results

We implemented and applied game theoretic centrality to rank genes on whole genomes from 756 multiplex autism families. Top ranking genes with the highest game theoretic centrality in both the weighted and unweighted approaches were enriched for pathways previously associated with autism, including pathways of the immune system. Four of the selected genes HLA-A, HLA-B, HLA-G, and HLA-DRB1–have also been implicated in ASD and further support the link between ASD and the human leukocyte antigen complex.

Conclusions

Game theoretic centrality can prioritize influential, disease-associated genes within biological networks, and assist in the decoding of polygenic associations to complex disorders like autism.
To bloom once or more times: the reblooming mechanisms of Iris germanica revealed by transcriptome profiling
Authors: Fan Zhuping , Gao Yike , Ren Yi , Guan Chunjing , Liu Rong , Zhang Qixiang
Published: August 2020

Background

The reblooming bearded iris (Iris germanica) can bloom twice a year, in spring and autumn. The extended ornamental period makes it more popular and brings additional commercial values. However, little is known about the reblooming mechanisms, making the breeding programs time-consuming and labor-wasting. Therefore, a comparative transcriptome profiling was conducted on once-bloomers and rebloomers from the same F1 generation on six development stages, and the candidate genes associated with reblooming were identified.

Results

A total of 100,391 unigenes were generated, the mean length being 785 bp. In the three comparisons (the floral initiation stage of spring flowering in once-bloomers (OB-T1) vs the floral initiation stage of spring flowering in rebloomers (RB-T1); RB-T1 vs the floral initiation stage of autumn flowering in rebloomers (RB-T5); OB-T1 vs RB-T5), a total of 690, 3515 and 2941 differentially expressed genes (DEGs) were annotated against the public databases, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis focused on the photoperiod response, the temperature insensitivity and the growth speed, to remove the redundant DEGs and figure out the candidate key genes. As a result, the following four genes, PHYTOCHROME A (PHYA), GIGANTEA (GI), SHORT VEGETATIVE PERIOD (SVP) and AUXIN RESPONSE FACTOR (ARF), were considered to be involved in the second floral initiation of the rebloomers.

Conclusion

This research provides valuable information for the discovery of the reblooming-related genes. The insights into the molecular mechanisms of reblooming may accelerate the breeding of bearded iris and other perennials.
Gut microbiome of endangered Tor putitora (Ham.) as a reservoir of antibiotic resistance genes and pathogens associated with fish health
Authors: Khurana Himani , Singh Durgesh Narain , Singh Anoop , Singh Yogendra , Lal Rup , Negi Ram Krishan
Published: August 2020

Background

Tor putitora, the largest freshwater fish of the Indian subcontinent, is an endangered species. Several factors have been attributed towards its continuous population decrease, but very little is known about the gut microbiome of this fish. Also, the fish gut microbiome serves as a reservoir of virulence factors and antibiotic resistance determinants. Therefore, the shotgun metagenomic approach was employed to investigate the taxonomic composition and functional potential of microbial communities present in the gut of Tor putitora, as well as the detection of virulence and antibiotic resistance genes in the microbiome.

Results

The analysis of bacterial diversity showed that Proteobacteria was predominant phylum, followed by Chloroflexi, Bacteroidetes, and Actinobacteria. Within Proteobacteria, Aeromonas and Caulobacter were chiefly present; also, Klebsiella, Escherichia, and plant symbionts were noticeably detected. Functional characterization of gut microbes endowed the virulence determinants, while surveillance of antibiotic resistance genes showed the dominance of β-lactamase variants. The antibiotic-resistant Klebsiella pneumoniae and Escherichia coli pathovars were also detected. Microbial genome reconstruction and comparative genomics confirmed the presence of Aeromonads, the predominant fish pathogens.

Conclusions

Gut microbiome of endangered Tor putitora consisted of both commensals and opportunistic pathogens, implying that factors adversely affecting the non-pathogenic population would allow colonization and proliferation of pathogens causing diseased state in asymptomatic Tor putitora. The presence of virulence factors and antibiotic resistance genes suggested the potential risk of dissemination to other bacteria due to horizontal gene transfer, thereby posing a threat to fish and human health. The preservation of healthy gut microflora and limited use of antibiotics are some of the prerequisites for the conservation of this imperilled species.
A randomised dose-response study of prophylactic Methoxamine infusion for preventing spinal-induced hypotension during Cesarean delivery
Authors: Fu Feng , Tang Yu-wen , Chen Hong , Jiao Cui-cui , Ma Na , Chen Xin-zhong
Published: August 2020

Background

α-receptor agonists have been reported to be safe and effective for treating or preventing spinal-induced hypotension during cesarean delivery. As a pure α1 adrenergic agonist, methoxamine has potential advantages of reducing myocardial oxygen consumption and protecting the heart in obstetric patients compared to phenylephrine. The aim of this study was to determine the optimal prophylactic methoxamine infusion dose that would be effective for preventing spinal-induced hypotension in 50% (ED50) and 95% (ED95) of parturients.

Methods

Eighty parturients with a singleton pregnancy scheduled for elective cesarean delivery were randomly allocated to receive prophylactic methoxamine infusion at one of four different fixed-rates: 1 μg/kg/min (group M1), 2 μg/kg/min (group M2), 3 μg/kg/min (group M3), or 4 μg/kg/min (group M4). An adequate response was defined as absence of hypotension (maternal SBP < 80% of baseline or SBP < 90 mmHg). The values for ED50 and ED95 of prophylactic methoxamine infusion were determined by probit regression model. The outcomes of maternal hemodynamics and fetal status were compared among the groups.

Results

The calculated ED50 and ED95 (95% confidence interval) of prophylactic methoxamine infusion dose were 2.178 (95% CI 1.564 to 2.680) μg/kg/min and 4.821 (95% CI 3.951 to 7.017) μg/kg/min, respectively. The incidence of hypotension decreased with increasing methoxamine infusion dose (15/20, 11/20, 7/20 and 2/20 in group M1, M2, M3 and M4 respectively, P <  0.001). 1-min Apgar scores and umbilical arterial PaO2 were lower but umbilical arterial PaCO2 was higher in Group M1. No difference was found in the other incidence of adverse effects and neonatal outcomes among groups.

Conclusions

Under the conditions of this study, when prophylactic methoxamine infusion was given at a fixed-rate based on body weight for preventing spinal-induced hypotension in obstetric patients, the values for ED50 and ED95 were 2.178 μg/kg/min and 4.821 μg/kg/min respectively.

Clinical trial registration

Chinese Clinical Trial Registry (ChiCTR), registry number of clinical trial: ChiCTR-1,800,018,988, date of registration: October 20, 2018.
A four-step strategy for handling missing outcome data in randomised trials affected by a pandemic
Authors: Cro Suzie , Morris Tim P. , Kahan Brennan C. , Cornelius Victoria R. , Carpenter James R.
Published: August 2020

Background

The coronavirus pandemic (Covid-19) presents a variety of challenges for ongoing clinical trials, including an inevitably higher rate of missing outcome data, with new and non-standard reasons for missingness. International drug trial guidelines recommend trialists review plans for handling missing data in the conduct and statistical analysis, but clear recommendations are lacking.

Methods

We present a four-step strategy for handling missing outcome data in the analysis of randomised trials that are ongoing during a pandemic. We consider handling missing data arising due to (i) participant infection, (ii) treatment disruptions and (iii) loss to follow-up. We consider both settings where treatment effects for a ‘pandemic-free world’ and ‘world including a pandemic’ are of interest.

Results

In any trial, investigators should; (1) Clarify the treatment estimand of interest with respect to the occurrence of the pandemic; (2) Establish what data are missing for the chosen estimand; (3) Perform primary analysis under the most plausible missing data assumptions followed by; (4) Sensitivity analysis under alternative plausible assumptions. To obtain an estimate of the treatment effect in a ‘pandemic-free world’, participant data that are clinically affected by the pandemic (directly due to infection or indirectly via treatment disruptions) are not relevant and can be set to missing. For primary analysis, a missing-at-random assumption that conditions on all observed data that are expected to be associated with both the outcome and missingness may be most plausible. For the treatment effect in the ‘world including a pandemic’, all participant data is relevant and should be included in the analysis. For primary analysis, a missing-at-random assumption – potentially incorporating a pandemic time-period indicator and participant infection status – or a missing-not-at-random assumption with a poorer response may be most relevant, depending on the setting. In all scenarios, sensitivity analysis under credible missing-not-at-random assumptions should be used to evaluate the robustness of results. We highlight controlled multiple imputation as an accessible tool for conducting sensitivity analyses.

Conclusions

Missing data problems will be exacerbated for trials active during the Covid-19 pandemic. This four-step strategy will facilitate clear thinking about the appropriate analysis for relevant questions of interest.
Disease progression of cancer patients during COVID-19 pandemic: a comprehensive analytical strategy by time-dependent modelling
Authors: Bhattacharjee Atanu , Vishwakarma Gajendra K. , Banerjee Souvik , Shukla Sharvari
Published: August 2020

Background

As the whole world is experiencing the cascading effect of a new pandemic, almost every aspect of modern life has been disrupted. Because of health emergencies during this period, widespread fear has resulted in compromised patient safety, especially for patients with cancer. It is very challenging to treat such cancer patients because of the complexity of providing care and treatment, along with COVID-19. Hence, an effective treatment comparison strategy is needed. We need to have a handy tool to understand cancer progression in this unprecedented scenario. Linking different events of cancer progression is the need of the hour. It is a huge challenge for the development of new methodology.

Methods

This article explores the time lag effect and makes a statistical inference about the best experimental arm using Accelerated Failure Time (AFT) model and regression methods. The work is presented as the occurrence of other events as a hazard rate after the first event (relapse). The time lag effect between the events is linked and analysed.

Results

The results were presented as a comprehensive analytical strategy by joining all disease progression. An AFT model applied with the transition states, and the dependency structure between the gap times was used by the auto-regression model. The effects of arms were compared using the coefficient of auto-regression and accelerated failure time (AFT) models.

Conclusions

We provide the solutions to overcome the issue with intervals between two consecutive events in motivating head and neck cancer (HNC) data. COVID-19 is not going to leave us soon. We have to conduct several cancer clinical trials in the presence of COVID-19. A comprehensive analytical strategy to analyse cancer clinical trial data during COVID-19 pandemic is presented.
Effect of financial stress on self-rereported health and quality of life among older adults in five developing countries: a cross sectional analysis of WHO-SAGE survey
Authors: Huang Rui , Ghose Bishwajit , Tang Shangfeng
Published: August 2020

In developing countries, older adults (65 years of age and above) share an increased vulnerability to catastrophic health expenditures and financial stress which can have significant bearing on their health and well-being. Currently, research evidence on how financial stress correlates with health and well-being among older adults in the developing countries is limited. Therefore, in this study, we aimed to assess the relationship between financial stress and subjective 1) health, 2) depression, 3) quality of life, and 4) life satisfaction among older adults in five developing countries.

Methods

Data used in this study were cross-sectional which were collected from the first wave of Study on Global AGEing and Health (SAGE) survey of World Health Organization. Sample population were 12,299 community dwelling men and women in China (n = 4548), Ghana (n = 1968), India (n = 2441), South Africa (n = 1924), and Russia (n = 1418). Using generalized linear models with logit links, we assessed the correlation between self-reported financial stress and income inequality with the four outcome measures by adjusting for various sociodemographic factors.

Results

Overall, the prevalence of good self-reported health, quality of life and positive life-satisfaction was 47.11, 79.25 and 44.40% respectively, while 20.13% of the participants reported having depression during past 12 months. Only about a fifth (18.67%) of the participants reported having enough money to meet daily their necessities completely, while more than quarter (28.45%) were in the lowest income quintile. With a few exceptions, the odds of reporting good self-reported health, quality of life, and life satisfaction were generally lower among those with varying degrees of financial stress, and larger among those in the higher income quintiles. Conversely, the likelihood of self-reported depression was significantly higher among those with any level of financial stress, and lower among those in the higher income quintiles.

Conclusion

This study concludes that both subjectively and objectively measured financial stress are inversely associated with good self-reported health, quality of life, life satisfaction, and positively associated with self-reported depression among older adults.
Genetic diversity of group A rotavirus in acute gastroenteritis outpatients in Shanghai from 2017 to 2018
Authors: Kuang Xiaozhou , Gong Xiaohuan , Zhang Xi , Pan Hao , Teng Zheng
Published: August 2020

Background

Group A Rotavirus (RVA), despite being an important pathogen in hospitalized children, is less studied in pediatric outpatients, and even rarely investigated in adults. This study aims to understand the genetic diversity of RVA in outpatients across all age groups in Shanghai, and thus providing a molecular basis for vaccine implementation and evaluation.

Methods

Stool samples were first screened by Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR). RVA genotyping was performed through the amplification of partial VP7 and VP4 gene. Strains of interest were further sequenced and analyzed using MEGA 6.0.

Results

Four thousand nine hundred one samples were collected, from which 7.61% (373 cases) were screened positive for RVA. RVA prevalence was higher in children (9.30%) than in adults (7.21%) (χ2 = 4.72,P < 0.05). 9.38% RVA positive cases had taken antibiotics before hospital visit while 49.60% had been prescribed antibiotics afterwards. RVA displayed a strong seasonality in both adults and children with a shared commonality in genotype repertoire, where G9P[8] was the most prevalent strain (67.96%) followed by G3P[8] (15.49%) and G1P[8] (12.32%). Meanwhile the first local case of fecal shedding of the G10P[15] vaccine strain was also discovered.

Conclusions

While the prevalence of rotavirus is highest during cold seasons, it is revealed for the first time that G9P[8] is the predominant genotype in both adults and pediatric outpatients. Clinically, higher occurrence of nausea or vomiting was observed in RVA positive cases. Antibiotic overuse was implicated in both non-clinical and clinical settings. The finding emphasizes the importance of RVA genotyping in surveillance as it provides the basis for new vaccine application as well as a baseline for future vaccine efficacy evaluation.
Predictors of tuberculosis infection among adults visiting anti-retroviral treatment center at east and west Gojjam, northwest, Ethiopia, 2017
Authors: Belew Habtamu , Wubie Moges , Tizazu Getaye , Bitew Abebaw , Birlew Tesfa
Published: August 2020

Background

Tuberculosis is a serious health risk, for people living with human immune deficiency virus worldwide, and the burden of TB/HIV infection is still high in Ethiopia in particular. Therefore, the aim of this study was to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in East and West Gojjam, northwest, Ethiopia.

Methods

Institution based unmatched case-control study was employed to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in east and west Gojjam, Northwest, Ethiopia from March 7–April 15, 2017. Just about 552 participants were participated in the study (139 Cases and 413 controls). Cases were confirmed with active TB and infected with HIV, and controls were HIV positive adults with non-TB. All cases in each health facility who confirmed by acid-fast bacilli, culture and gene expert were considered as TB positive. However, controls were selected by using simple random sampling technique through the above diagnostic criteria and the data were collected with Face to face interview as well as patient medical record were utilized, and the quality of the data were assured, checked, coded, cleaned and entered in EPI-Data version 3.1 and exported to SPSS version 20 for the analysis.

Result

Of the total sample (556), just about 552(99.2%) were participated in the study. 47.5% were females and 58.9% were rural dweller. Behavioral and modifiable biological risk factors: alcohol users (AOR = 2.33; 95%CI:1.34,4.07), BMI < 18.5 kg/m2(AOR = 3.03;95%CI:1.79,5.14), CD4 count ≤200 cells/μl (AOR = 2.34;95%CI:1.89,2.79) and between 201 and 499 cells/μl (AOR = 2.63; 95%CI: 1.01,6.84), bedridden and ambulatory (AOR = 3.3;95%CI:1.70,6.29 and AOR = 8.2;95%CI:4.34,15.64), respectively. TB history in the family (AOR = 3.00; 95%CI: 1.57, 5.74) were predictors for TB infection. Taking CPT (AOR = 0.36; 95%CI: 0.21, 0.62) and having early WHO clinical stage I or II (AOR = 0.34; 95%CI: 0.20, 0.56) had protective effect against TB infection.

Conclusion

From this study, it has been concluded that alcohol users, BMI < 18.5 kg/m2, CD4 count < 499 cells/μl, bedridden and ambulatory and TB history were predictors for TB-HIV co-infected adults. Strengthen screening more frequently, CPT Prophlaxysis and treated promptly important to reduce TB co-morbidity.
Renal proximal tubulopathy in an HIV-infected patient treated with tenofovir alafenamide and gentamicin: a case report
Authors: Heron Jack E. , Bloch Mark , Vanguru Vinay , Saunders John , Gracey David M.
Published: August 2020

Background

The nucleotide reverse transcriptase inhibitor Tenofovir Alafenamide (TAF) is a novel pro-drug of tenofovir (TFV) and possesses a superior renal safety profile compared with tenofovir disoproxil fumerate (TDF). Due to unique pharmacokinetic characteristics, treatment with TAF is not associated with significant renal proximal tubular accumulation of TFV. TAF is associated with a lower risk of acute kidney injury, chronic kidney disease, proteinuria and renal proximal tubular dysfunction than treatment with TDF. No cases of Fanconi syndrome have been reported in clinical trials of TAF. It is unknown whether treatment with TAF can lead to accumulation of TFV in proximal tubular cells and cause nephrotoxicity under certain clinical circumstances.

Case presentation

Here we report the case of a patient on stable TAF-based antiretroviral therapy with for HIV-1 infection who developed proximal tubulopathy when treated with gentamicin for febrile neutropenia in the context of relapsed Hodgkin lymphoma. Eighteen days after commencing chemotherapy for relapsed Hodgkin lymphoma the patient presented to hospital with fevers, hypotension and neutropenia. The patient was commenced on piperacillin, tazobactam and gentamicin. Within 24 h the patient developed marked hypokalaemia and hypophosphataemia requiring intravenous replacement therapy. There was proteinuria, glycosuria and evidence of marked urinary electrolyte wasting, consistent with acute proximal tubular dysfunction. Eleven days after the gentamicin was stopped the serum biochemistry normalised. The urinary electrolyte wasting and proteinuria had improved, and the glycosuria had resolved.

Conclusion

This is the first case report to describe acute renal proximal tubulopathy in an HIV-infected patient treated with TAF and gentamicin. As the number of patients prescribed TAF outside the clinical trial setting increases, so too does the potential for previously unreported drug interactions and adverse events. Clinicians need to be aware of potential unreported adverse drug reactions as the use of TAF becomes increasingly common in clinical practice.
Adequacy and complication rates of percutaneous renal biopsy with 18- vs. 16-gauge needles in native kidneys in Chinese individuals
Authors: Xie Weiji , Xu Jing , Xie Yi , Lin Zhijun , Xu Xiaochang , Zhang Xialan , Zhang Yimin
Published: August 2020

Background

Percutaneous renal biopsy (PRB) is the primary biopsy technique and it was used by 16G needles or 18G needles in China, but there is controversy about the effect and safety of the two different diameters. The study aims to compare the adequacy, complication rate and pathological classification when using 18G vs. 16G needles to perform renal biopsy with ultrasound-guidedance on native kidneys in Chinese individuals.

Methods

We retrospectively analyzed the number of glomeruli, adequate sample rates, complication rates and pathological classification in 270 patients with the use of 18G or 16G needles from January 2011 to May 2017 and verified whether the needle gauge affected the disease diagnosis.

Results

A total of 270 kidney biopsies were performed. Among them,72 were performed with 18G needles, and 198 were performed with 16G needles. There was no difference in the number of glomeruli under light microscope using 18G relative to 16G needles (24 ± 11 vs. 25 ± 11,p = 0.265), whereas more glomeruli were found in the 16G group than in the 16G group using immunofluorescence microscopy (3 ± 2 vs. 5 ± 3,p < 0.05). There was no significant difference in the adequate sample rates between the 18G group and the 16G group (90.28% vs. 93.94%,p = 0.298). Minor complications including the incidence of lumbar or abdominal pain (4.17% vs. 7.07%,p = 0.57), gross hematuria (4.17% vs. 3.54%,p = 0.729), and perinephric hematoma without symptoms (4.17% vs. 1.52%,p = 0.195), were not significantly different between the 18G and 16G groups. In the 16G group, 2 cases of serious complications occurred: severe gross hematuria requiring blood transfusion and retroperitoneal hematoma requiring surgery. No serious complications were observed in the 18G group, although there was no significant difference in serious complications rates between the 18G and 16G groups (0% vs. 1.02%,p = 1).

Conclusion

There was no significant difference in the number of glomeruli, adequate sample rates, or complication rates when using 18G or 16G needles to perform renal biopsy, and the use of an 18G needle with a smaller diameter did not affect the pathological diagnosis or classification of IgA nephropathy and lupus nephritis.
Maternal perceptions of the experience of attempted labor induction and medically elective inductions: analysis of survey results from listening to mothers in California
Authors: Declercq Eugene , Belanoff Candice , Iverson Ronald
Published: August 2020

Background

The rate of induction of labor in the U.S. has risen from 9.6% in 1990 to 25.7% in 2018, including 31.7% of first-time births. Recent studies that have examined inductions have been small qualitative studies or relied on either medical records or administrative data. This study examines induction from the perspective of those women who experienced it, with a particular focus on the prevalence and predictors of inductions for nonmedical indications, women’s experience of pressure to induce labor and the relationship between the attempt to medically initiate labor and cesarean section.

Methods

Study data are drawn from the 2119 respondents to theListening to Mothers in Californiasurvey who were planning to have a vaginal birth in 2016. Mothers were asked if there had been an attempt to medically initiate labor, if it actually started labor, if they felt pressured to have the induction, if they had a cesarean and the reason for the induction. Reasons for induction were classified as either medically indicated or elective.

Results

Almost half (47%) of our respondents indicated an attempt was made to medically induce their labor, and 71% of those attempts initiated labor. More than a third of the attempts (37%) were elective. Attempted induction overall was most strongly associated with giving birth at 41+ weeks (aOR 3.28; 95% C.I. 2.21–4.87). Elective inductions were more likely among multiparous mothers and in pregnancies at 39 or 40 weeks. The perception of being pressured to have labor induced was related to higher levels of education, maternal preference for less medical intervention in birth, having an obstetrician compared to a midwife and gestational ages of 41+ weeks. Cesarean birth was more likely in the case of overall induction (aOR 1.51; 95% C.I. 1.11–2.07) and especially following a failed attempt at labor induction (aOR 4.50; 95% C.I. 2.93–6.90).

Conclusion

Clinicians counselling mothers concerning the need for labor induction should be aware of mothers’ perceptions about birth and engage in true shared decision making in order to avoid the maternal perception of being pressured into labor induction.
Perinatal and neonatal outcomes of pregnancies after early rescue intracytoplasmic sperm injection in women with primary infertility compared with conventional intracytoplasmic sperm injection: a retrospective 6-year study
Authors: Xiong Feng , Sun Qing , Li Guangui , Yao Zhihong , Chen Peilin , Wan Caiyun , Zhong Huixian , Zeng Yong
Published: August 2020

Background

Early rescue intracytoplasmic sperm injection (ICSI) has been used in clinic as appropriate currently. While the outcomes of children born after this method were not well assessed. The purpose of this study was to evaluate the effect of early rescue ICSI on women with primary infertility.

Methods

Fresh embryo transfer cycles after rescue (n = 214) and conventional (n = 546) ICSI were retrospectively evaluated from women with primary infertility who underwent their first assisted reproductive technology cycles at our center in 2012–2017. The conventional ICSI group was subdivided into ICSI-1 (semen suitable for in vitro fertilization, IVF) and ICSI-2 (poor semen quality) to minimize bias from differences in semen quality. Pregnancy, delivery and neonatal outcomes were compared between groups.

Results

There was a higher rate of polyspermy and a lower rate of top-quality embryos (TQE) on day 3 for oocytes subject to rescue ICSI compared with conventional ICSI. This reduced the total number of TQE and the number of TQE transferred in the rescue ICSI group. There was no significant difference between groups in clinical pregnancy, ongoing pregnancy, early miscarriage and live birth. For pregnant women, gestational age, route of delivery, risk of preterm birth and gestational diabetes mellitus were also comparable. Neonatal outcomes including sex ratio, birth weight, neonatal intensive care unit admission and birth defects were also similar after rescue and conventional ICSI. Moreover, no differences were observed with the different ICSI subgroups.

Conclusions

For women with primary infertility who have a high risk of IVF fertilization failure (FF), rescue ICSI provides a safe and efficient alternative to minimize FF after initial IVF, but results in fewer TQE on day 3.
Breast cancer diagnosis is associated with relative left ventricular hypertrophy and elevated endothelin-1 signaling
Authors: Maayah Zaid H. , Takahara Shingo , Alam Abrar S. , Ferdaoussi Mourad , Sutendra Gopinath , El-Kadi Ayman O. S. , Mackey John R. , Pituskin Edith , Paterson D. Ian , Dyck Jason R. B.
Published: August 2020

Background

The survival rates of women with breast cancer have improved significantly over the last four decades due to advances in breast cancer early diagnosis and therapy. However, breast cancer survivors have an increased risk of cardiovascular complications following chemotherapy. While this increased risk of later occurring structural cardiac remodeling and/or dysfunction has largely been attributed to the cardiotoxic effects of breast cancer therapies, the effect of the breast tumor itself on the heart prior to cancer treatment has been largely overlooked. Thus, the objectives of this study were to assess the cardiac phenotype in breast cancer patients prior to cancer chemotherapy and to determine the effects of human breast cancer cells on cardiomyocytes.

Methods

We investigated left ventricular (LV) function and structure using cardiac magnetic resonance imaging in women with breast cancer prior to systemic therapy and a control cohort of women with comparable baseline factors. In addition, we explored how breast cancer cells communicate with the cardiomyocytes using cultured human cardiac and breast cancer cells.

Results

Our results indicate that even prior to full cancer treatment, breast cancer patients already exhibit relative LV hypertrophy (LVH). We further demonstrate that breast cancer cells likely contribute to cardiomyocyte hypertrophy through the secretion of soluble factors and that at least one of these factors is endothelin-1.

Conclusion

Overall, the findings of this study suggest that breast cancer cells play a greater role in inducing structural cardiac remodeling than previously appreciated and that tumor-derived endothelin-1 may play a pivotal role in this process.
When to call it off: defining transplant candidacy limits in liver donor liver transplantation for hepatocellular carcinoma
Authors: Bhatti Abu Bakar Hafeez , Qureshi Ammal Imran , Tahir Rizmi , Dar Faisal Saud , Khan Nusrat Yar , Zia Haseeb Haider , Riyaz Shahzad , Rana Atif
Published: August 2020

Background

Living donor liver transplantation (LDLT) is an acceptable treatment option for hepatocellular carcinoma (HCC). Traditional transplant criteria aim at best utilization of donor organs with low risk of post transplant recurrence. In LDLT, long term recurrence free survival (RFS) of 50% is considered acceptable. The objective of the current study was to determine preoperative factors associated with high recurrence rates in LDLT.

Methods

Between April 2012 and December 2019, 898 LDLTs were performed at our center. Out of these, 242 were confirmed to have HCC on explant histopathology. We looked at preoperative factors associated with ≤ 50%RFS at 4 years. For survival analysis, Kaplan Meier curves were used and Cox regression analysis was used to identify independent predictors of recurrence.

Results

Median AFP was 14.4(0.7–11,326.7) ng/ml. Median tumor size was 2.8(range = 0.1–11) cm and tumor number was 2(range = 1–15). On multivariate analysis, AFP > 600 ng/ml [HR:6, CI: 1.9–18.4,P = 0.002] and microvascular invasion (MVI) [HR:5.8, CI: 2.5–13.4,P <  0.001] were independent predictors of 4 year RFS ≤ 50%. When AFP was > 600 ng/ml, MVI was seen in 88.9% tumors with poor grade and 75% of tumors outside University of California San Francisco criteria. Estimated 4 year RFS was 78% for the entire cohort. When AFP was < 600 ng/ml, 4 year RFS for well-moderate and poor grade tumors was 88 and 73%. With AFP > 600 ng/ml, RFS was 53% and 0 with well-moderate and poor grade tumors respectively (P <  0.001).

Conclusion

Patients with AFP < 600 ng/ml have acceptable outcomes after LDLT. In patients with AFP > 600 ng/ml, a preoperative biopsy to rule out poor differentiation should be considered for patient selection.
Impact on quality of life 3 years after diagnosis of prostate cancer patients below 75 at diagnosis: an observational case-control study
Authors: Houédé Nadine , Rébillard Xavier , Bouvet Sophie , Kabani Sarah , Fabbro-Peray Pascale , Trétarre Brigitte , Ménégaux Florence
Published: August 2020

Background

Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression.

Methods

Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects.

Results

In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151).

Conclusions

Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients < 75 years at diagnosis. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction.

Trial registration

clinicaltrials.gov, NCT02854982. Registered 4 August 2016, retrospectively registered.
Evidence for disruption of diurnal salivary cortisol rhythm in childhood obesity: relationships with anthropometry, puberty and physical activity
Authors: Yu Ting , Zhou Wei , Wu Su , Liu Qianqi , Li Xiaonan
Published: August 2020

Background

The aim of this study was to examine the characteristics of diurnal cortisol rhythm in childhood obesity and its relationships with anthropometry, pubertal stage and physical activity.

Methods

Thirty-five children with obesity (median age: 11.80[interquartile range 10.30, 13.30] and median BMI z-score: 3.21[interquartile range 2.69, 3.71]) and 22 children with normal weight (median age: 10.85[interquartile range 8.98, 12.13] and median BMI z-score: − 0.27[interquartile range − 0.88, 0.35]) were recruited. Saliva samples were collected at 08:00, 16:00 and 23:00 h. Cortisol concentrations at 3 time points, corresponding areas under the curve (AUCs) and diurnal cortisol slope (DCS) were compared between the two groups. Anthropometric measures and pubertal stage were evaluated, and behavioural information was obtained via questionnaires.

Results

Children with obesity displayed significantly lower cortisol08:00 (median [interquartile range]: 5.79[3.42,7.73] vs. 8.44[5.56,9.59] nmol/L, P = 0.030) and higher cortisol23:00 (median [interquartile range]: 1.10[0.48,1.46] vs. 0.40[0.21,0.61] nmol/L, P < 0.001) with a flatter DCS (median [interquartile range]: − 0.29[− 0.49, 0.14] vs. -0.52[− 0.63, 0.34] nmol/L/h, P = 0.006) than their normal weight counterparts. The AUC increased with pubertal development (AUC08:00–16:00:P = 0.008; AUC08:00–23:00: P = 0.005). Furthermore, cortisol08:00 was inversely associated with BMI z-score (β = − 0.247, P = 0.036) and waist-to-height ratio (WHtR) (β = − 0.295, P = 0.027). Cortisol23:00 was positively associated with BMI z-score (β = 0.490, P<0.001), WHtR (β = 0.485, P<0.001) and fat mass percentage (FM%) (β = 0.464, P<0.001). Absolute values of DCS were inversely associated with BMI z-score (β = − 0.350, P = 0.009), WHtR (β = − 0.384, P = 0.004) and FM% (β = − 0.322, P = 0.019). In multivariate analyses adjusted for pubertal stage and BMI z-score, Cortisol08:00, AUC08:00–16:00 and absolute values of DCS were inversely associated with the relative time spent in moderate to vigorous intensity physical activity (P < 0.05). AUC16:00–23:00 was positively associated with relative non-screen sedentary time and negatively associated with sleep (P < 0.05).

Conclusions

The disorder of diurnal salivary cortisol rhythm is associated with childhood obesity, which is also influenced by puberty development and physical activity. Thus, stabilizing circadian cortisol rhythms may be an important approach for childhood obesity.
Child maltreatment-related dissociation and its core mediation schemas in patients with borderline personality disorder
Authors: Khosravi Mohsen
Published: August 2020

Background

From a developmental and pathogenic perspective, child maltreatment is strongly linked to later dissociative symptoms, as ultimate forms of human response to chronic stress. The present study aimed to investigate the mediating role of early maladaptive schemas (EMSs) in the relationship between child maltreatment and dissociation among patients with borderline personality disorder (BPD).

Methods

In this cross-sectional study, a total of 152 BPD patients (men: 52%; women: 48%) with an average age of 29.64 years (standard deviation (SD) = 7.29, range = 18–47) were selected by systematic random sampling from the patients who referred to Baharan psychiatric hospital in Zahedan, Iran, with the sampling interval of 3. The Childhood Trauma Questionnaire-Short Form, Dissociative Experiences Scale, and Young Schema Questionnaire-Short Form 3 were used to assess the patients. Data were analyzed using SPSS v25 software, and the statistical significance level was set at p < 0.05.

Results

four main findings were obtained from the present study: (1) Heterogeneity of the levels of dissociation (LOD) in BPD patients; (2) The predicting roles of emotional neglect (EN), vulnerability to harm, and defectiveness/shame schemas in the total DES scores; (3) The vague role of childhood sexual abuse (SA) in developing dissociative symptoms; and (4) The mediating role of the core schemas of vulnerability to harm (β = 0.28, 95% confidence interval (CI): 0.04, 0.61) and defectiveness/shame (β = 0.21, 95% CI: 0.008, 0.45) in the relationship between EN and dissociation.

Conclusions

Regarding the heterogeneity of LOD and its crucial role in the successful treatment of BPD patients, it is highly essential to evaluate the present-state dissociation of the patient during the diagnosis process and provide effective interventions to reduce it. The obtained results highlighted the potential role of schema therapy in reducing dissociative responses to emotional stimuli (based on EN), vulnerability to harm, and defectiveness/shame. Nevertheless, psychopathology of dissociation among BPD patients should be further investigated in depth.
Correction to: Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) – a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial
Authors: Chalder Trudie , Patel Meenal , James Kirsty , Hotopf Matthew , Frank Philipp , Watts Katie , McCrone Paul , David Anthony , Ashworth Mark , Husain Mujtaba , Garrood Toby , Moss-Morris Rona , Landau Sabine
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.