bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurse and allied health professional experiences and attitudes toward critical care research: A national questionnaire study
Authors: Battle Ceri , Lynch Ceri , Discroll Timothy , Thorpe Chris , Hatchley Bryony , Biggs Sara , Phillips Rebecca , Roberts Alice , Roberts Sian , Cole Jade , Davies Rhys , Hobrok Maria , Canning David , Littler Christopher , Williams Anwen , Pugh Richard
Published: October 2020

Introduction

The aim of this study was to investigate nurse and allied health professional experiences and attitudes toward critical care research in Wales.

Methods

Data were collected related to demographic characteristics, involvement in and understanding of research, perceived influences and attitudes towards research. We calculated means (ranges) for continuous variable and frequencies (proportions) for discrete variables and performed an exploratory factor analysis.

Results

Response rate was 55% ( n = 575). Most respondents (84%) had participated in research less than five times in the previous 12 months, yet 91% believed research led to improved care patients. Only 32% respondents felt they were encouraged by managers to participate in research. Only 25% respondents had undertaken research training. Few respondents (29%) reported receiving adequate information regarding study progress or results (25%). Linear regression models indicate that a higher level of formal education was associated with a more positive view of research across all attitude factors. Promotion of research by colleagues and recognition/ opportunities for involvement in critical care research, were positively associated with the acceptability and experience of research.

Discussion

A number of factors have been identified that could be targeted to improve recruitment to critical care research, including identification of staff to promote research, improved communication of study progress and findings and management encouragement to attend research training. Staff attitudes were positive towards the benefit of research on patient care in Wales.
Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study
Authors: Procopio Giuseppe , Chiuri Vincenzo Emanuele , Giordano Monica , Mantini Giovanna , Maisano Roberto , Bordonaro Roberto , Calvani Nicola , Facchini Gaetano , De Placido Sabino , Airoldi Mario , Sbrana Andrea , Gasparro Donatello , Ludovico Giuseppe Mario , Guglielmini Pamela , Naglieri Emanuele , Fagnani Daniele , Aglietta Massimo , Schips Luigi , Beccaglia Patrizia , Sciarra Alessandro , Livi Lorenzo , Santini Daniele
Published: October 2020

Background:

Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies.

Methods:

ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined.

Results:

In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone.

Conclusions:

Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.
A systematic review of how daily activities and exercises are recommended following volar plating of distal radius fractures and the efficacy and safety of early versus late mobilisation
Authors: Collis Julie , Signal Nada , Mayland Elizabeth , Clair Valerie Wright-St
Published: October 2020

Introduction

Following surgical repair of distal radius fractures, mobilisation timeframes and interventions vary. Early mobilisation (<2 weeks postoperatively) usually includes range of motion exercises and may include recommendations to perform daily activities. The review investigated (i) how early mobilisation was recommended, particularly with respect to wrist use during daily activities and (ii) the efficacy and safety of early versus delayed mobilisation (< or ≥2 weeks).

Methods

The study protocol was registered on PROSPERO (CRD42019136490). Five databases were searched for studies that compared early and delayed mobilisation in adults with volar plating of distal radius fractures. The Downs and Black Quality Index and the Template for Intervention Description and Replication checklist were used for quality evaluation. Effect sizes were calculated for range of movement, function and pain at 6–8, 10–12 and 26 weeks. A descriptive analysis of outcomes and mobilisation regimes was conducted.

Results

Eight studies with a mean Quality Index score of 20 out of 28 (SD=5.6) were included. Performing daily activities was commonly recommended as part of early mobilisation. Commencing mobilisation prior to two weeks resulted in greater range of movement, function and less pain at up to eight weeks postoperatively than delaying mobilisation until two weeks or later.

Discussion

Performance of daily activities was used alongside exercise to promote recovery but without clearly specifying the type, duration or intensity of activities. In combination with exercise, early daily activity was safe and beneficial. Performing daily activities may have discrete advantages. Hand therapists are challenged to incorporate activity-approaches into early mobilisation regimes.
Transconjunctival Approach Using Lateral Skin Extension for Reconstruction of Orbit Zygomatic Complex Fractures: Technique Description and a Case Series Analysis
Authors: Pérez Salvador Valladares , Correa Diego Bustamante , Fuentes Carlos Cortez , Mori Felipe Astorga , Troncoso Gerson Sepúlveda , Sirandoni Rodrigo Fariña
Published: October 2020

Study Design:

A descriptive-observational study of a series case report of patients diagnosed with orbito-zygomatic complex (OZMC) fracture with lateral wall involvement, was conducted. All patients were assessed in the Oral and Maxillofacial Surgery Service at Hospital El Carmen, Maipu, Santiago, Chile.

Objective:

The purpose of this study was to evaluate a single-institution experience with the transconjunctival approach to the orbit, utilizing a lateral skin extension as unique approach to access to fronto-zygomatic suture, infraorbital rim and/or orbital floor.

Method:

The authors identified 41 patients with OZMC fractures who underwent to surgical treatment over a 45 months period. Among this group, 21 patients needed fixation with osteosynthesis of the frontozygomatic suture, and 16 of whom were treated with the approach being studied. The authors assessed scleral exposure, eyelid position changes, ectropion, and entropion as outcome measures, and reported satisfactory outcomes at a minimum of 9 months follow-up.

Conclusions:

This study concludes that in our experience, the transconjunctival approach utilizing a lateral skin extension allows a direct, easy, and quick access to the entire infra orbital rim, orbital floor, fronto-zygomatic suture and lateral wall of the orbit, up to spheno-zygomatic suture, with low associated morbidity and complications.
Who Is Impacted? Personality Predicts Individual Differences in Psychological Consequences of the COVID-19 Pandemic in Germany
Authors: Modersitzki Nick , Phan Le Vy , Kuper Niclas , Rauthmann John F.
Published: October 2020

The COVID-19 pandemic has led to changes in people’s private and public lives that are unprecedented in modern history. However, little is known about the differential psychological consequences of restrictions that have been imposed to fight the pandemic. In a large and diverse German sample ( N = 1,320), we examined how individual differences in psychological consequences of the pandemic (perceived restrictiveness of government-supported measures, global pandemic-related appraisals, subjective well-being) were associated with a broad set of faceted personality traits (Big Five, Honesty-Humility, Dark Triad). Facets of Extraversion, Neuroticism, and Openness were among the strongest and most important predictors of psychological outcomes, even after controlling for basic sociodemographic variables (gender, age). These findings suggest that psychological consequences of the pandemic depend on personality and thus add to the growing literature on the importance of considering individual differences in crisis situations.
Rising Ethnic Diversity in the United States Accompanies Shifts Toward an Individualistic Culture
Authors: Huynh Alex C. , Grossmann Igor
Published: October 2020

We investigate the relationship between ethnic diversity and the rise of individualism in the United States during the 20th and 21st centuries. Tests of the historical rates of ethnic diversity alongside individualistic relational structures (e.g., adults living alone, single-/multi-child families) from the years 1950 to 2018 reveal that societal and regional rates of ethnic diversity accompanied individualistic relational structures. These effects hold above and beyond time-series trends in each variable. Further evidence from experimental studies ( N = 707) suggests that the presence of, and contact with, ethnically diverse others contributes to greater individualistic values (e.g., the importance of uniqueness and personal achievement). Converging evidence across societal-, regional-, and individual-level analyses suggests a systematic link between ethnic diversity and individualism. We discuss the implications of these findings for sociocultural livelihood in light of the rising rates of ethnic diversity across the globe.
Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis
Authors: Bsteh Gabriel , Hegen Harald , Altmann Patrick , Auer Michael , Berek Klaus , Pauli Franziska Di , Wurth Sebastian , Zinganell Anne , Rommer Paulus , Deisenhammer Florian , Leutmezer Fritz , Berger Thomas
Published: October 2020

Background

PIRA (progression independent of relapse) has emerged as a term to quantify the proportion of disability worsening due to non-inflammatory neurodegenerative processes in multiple sclerosis (MS).

Objective

To determine the impact of PIRA on retinal thinning, a biomarker of neuroaxonal degeneration in MS, in comparison to traditional disability worsening and relapse.

Methods

In a 4-year, prospective observational study including 171 relapsing MS (RMS) patients, retinal thinning was determined by annual spectral-domain optical coherence tomography measuring macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and peripapillary-retinal-nerve-fibre-layer (pRNFL). PIRA was defined as an expanded disability status scale (EDSS) or symbol digit modalities test (SDMT) worsening confirmed after 24 weeks with no relapse in the 30 days before or after the disability worsening.

Results

Each PIRA event was associated with a mean additional loss of GCIPL (1.8 µm) and pRNFL (1.9 µm), similar to the impact of EDSS and SDMT worsening. Overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3 µm) and pRNFL (1.4 µm).

Conclusions

PIRA is associated with retinal thinning, likely reflecting neurodegenerative processes, not directly associated with focal inflammation. It might be a clinical measure to identify MS patients with ongoing MS-associated neurodegeneration.
A surgical solution for a catamenial epilepsy medical therapy-resistant: A presumed case of cerebral endometriosis?
Authors: Antonio Maiorana , Walter Alio , Giorgia Ranieri , Anna Civiletto , Luigi Alio , Domenico Incandela
Published: October 2020

The presence of catamenial epilepsy in patients diagnosed with endometriosis is the symptom that would direct towards a suspected cerebral endometriotic localization. However, data research of medical literature supporting this diagnosis shows a small number of studies and the specific research on medline led to the finding of only four case reports. Hence forward, we will report a case of a patient with the surgical diagnosis of ovarian endometriosis, whom had signs of catamenial epilepsy resistant to medical therapy, and with contraindication to hormone therapy because of cerebral ischemic episodes, subjected to laparoscopic bilateral ovarosalpingectomy.
Upward Trends of Parotitis and Mumps in Atlanta over a Decade
Authors: Reddy Lankala M. , Bloch Deborah , Mallino Amanda , Kumari Polly , Figueroa Janet , Kendrick Lea , Chahroudi Ann , Tuttle Jessica , Thomas Ebony , Morris Claudia R.
Published: October 2020

Rising rates of mumps in Georgia have been reported. We hypothesize that the incidence of parotitis and mumps presenting to Children’s Healthcare of Atlanta (CHOA) has increased over the past decade among immunized children. Retrospective chart reviews were conducted using ICD9/10-codes for parotitis and mumps from January 2007 to December 2017. Data on demographics, vaccination status, labs, management and disposition were collected. 1017 parotitis cases were diagnosed; an upward trend in incidence occurred over time. Mumps testing was done in 47 (4.6%) parotitis cases; 9 mumps cases were identified, with 6 diagnosed in 2017. Seven patients (78%) were fully vaccinated. Median age for mumps was 13 years. Few symptoms differentiate mumps from non-mumps-parotitis. The incidence of parotitis and mumps in children has increased since 2007 in the Atlanta area, reflecting a nationwide trend. Mumps is likely underreported as rates of testing are low, and should be considered in children with parotitis regardless of vaccination history.
Reliability of Clinical DWI Mismatch Approach to Predict Patient With the Probability of Large Infarct Growth: A Comparison of the Percentage of Infarct Growth and Clinical DWI Mismatch Status of the Patients With Acute Ischemic Stroke
Authors: Christian Nganji , Ghanaati Hossein , Changizi Vahid , Siroos Bahaadin , Mousavi Farnoosh
Published: October 2020

Purpose:

The purpose of this study is to highlight the reliability of clinical DWI mismatch (CDM) in the identification of patients with large infarct growth.

Methods:

We prospectively reviewed 21 ischemic stroke patients who underwent DWI imaging within 72 hours from stroke symptoms onset. Description of images was made by experienced radiologists. Lesion volumes were assessed by manually outlining the DWI infarct lesions area. The percentage of infarct growth was calculated by dividing the difference between second and first infarct volume by the first infarct volume times 100. The NIHSS scores were assessed by an experienced neurologist. CDM was defined as NIHSS score ≥8 and initial infarct volume on DWI ≤ 25 mL.

Statistical Tests:

We assessed the relationships of variables within different groups of CDM using nonparametric tests—Kruskal-Wallis and chi-square test. Sensitivity and specificity of CDM to predict large infarct growth were tested by using crosstabs table.

Results:

CDM was present in 36.8% of our patients and was associated with the percentage of infarct growth ( P < .01). The mean percentage growth was high in patients with CDM (211.8%) while it was low in the group of patients without CDM (5.7%; group B and 10.7%; group C). The sensitivity and specificity of CDM to predict infarct growth was 77.8% vs 100% with a likelihood ratio of 15.4 ( P = .0004).

Conclusion:

The approach of comparing CDM and percentage of infarct growth proved that the concept of CDM can accurately indicate the existence of a large volume of tissue at risk of infarction—penumbra.
Impact of MYC and BCL2 structural variants in tumors of DLBCL morphology and mechanisms of false-negative MYC IHC
Authors: Collinge Brett J , Ben-Neriah Susana , Chong Lauren C. , Boyle Merrill , Jiang Aixiang , Miyata-Takata Tomoko , Farinha Pedro , Craig Jeffrey W , Slack Graham W. , Ennishi Daisuke , Mottok Anja , Meissner Barbara , Chavez Elizabeth A. , Gerrie Alina S. , Villa Diego , Freeman Ciara L. , Savage Kerry J. , Sehn Laurie H. , Morin Ryan D. , Mungall Andrew J , Gascoyne Randy D. , Marra Marco A. , Connors Joseph M , Steidl Christian , Scott David W.
Published: October 2020

When the WHO defined high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) as a clinical category, rearrangements were the only structural variant (SV) incorporated. An "atypical double-hit" entity has been proposed, encompassing tumors with concurrent MYC and BCL2 SVs other than co-occurring translocations - i.e. copy number variations (CNVs). While the identification of a gene expression signature (DHITsig) shared among tumors harboring MYC and BCL2 rearrangements (HGBL-DH/TH-BCL2) has confirmed a shared underlying biology, the biological implication of MYC and BCL2 CNVs requires further elucidation. We performed a comprehensive analysis of MYC and BCL2 SVs, as determined by fluorescent in situ hybridization (FISH), in a cohort of 802 de novo tumors with diffuse large B-cell lymphoma (DLBCL) morphology. While BCL2 CNVs were associated with increased expression, MYC CNVs were not. Furthermore, MYC and BCL2 CNVs, in the context of atypical double-hit, did not confer a similar gene expression profile as HGBL-DH/TH-BCL2. Finally, while MYC IHC has been proposed as a screening tool for FISH testing, two mechanisms were observed that uncoupled MYC rearrangement from IHC positivity. 1) low MYC mRNA expression and 2) false-negative immunohistochemistry (IHC) staining mediated by a single nucleotide polymorphism resulting in an asparagine to serine substitution at the 11th amino acid residue of MYC (MYC-N11S). Taken together, these results support the current exclusion of MYC and BCL2 CNVs from HGBL-DH/TH and highlight the ability of a molecular based classification system to identify tumors with shared biology that FISH and IHC fail to fully capture.
Transcriptomic and functional analyses reveal an antiviral role of autophagy during pepper mild mottle virus infection
Authors: Jiao Yubing , An Mengnan , Li Xiaodong , Yu Man , Zhao Xiuxiang , Xia Zihao , Wu Yuanhua
Published: October 2020

Background

Pepper mild mottle virus (PMMoV) is a member in the genus Tobamovirus and infects mainly solanaceous plants. However, the mechanism of virus-host interactions remains unclear. To explore the responses of pepper plants to PMMoV infection, we analyzed the transcriptomic changes in pepper plants after PMMoV infection using a high-throughput RNA sequencing approach and explored the roles of host autophagy in regulating PMMoV infection.

Results

A total of 197 differentially expressed genes (DEGs) were obtained after PMMoV infection, including 172 significantly up-regulated genes and 25 down-regulated genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that most up-regulated DEGs were involved in plant abiotic and biotic stresses. Further analyses showed the expressions of multiple autophagy-related genes (ATGs) were increased after PMMoV infection in pepper and Nicotiana benthamiana plants. Through confocal microscopy and transmission electron microscopy, we have found that PMMoV infection in plant can induce autophagy, evidenced by the increased number of GFP-ATG8a fluorescent punctate and the appearance of double membrane autophagic structures in cells of N. benthamiana. Additionally, inhibition of autophagy significantly increased PMMoV RNA accumulation and aggravated systemic PMMoV symptoms through autophagy inhibitor (3-MA and E64d) treatment and silencing of NbATG expressions by a Tobacco rattle virus-induced gene silencing assays. These results indicated that autophagy played a positive role in plant resistance to PMMoV infection.

Conclusions

Taken together, our results provide a transcriptomic insight into pepper responding to PMMoV infection and reveal that autophagy induced by PMMoV infection has an antiviral role in regulating PMMoV infection. These results also help us to better understand the mechanism controlling PMMoV infection in plants and to develop better strategies for breeding projects for virus-resistant crops.
Analysis of antibiotic treatment of children in a Shanghai tertiary hospital based on point prevalence surveys
Authors: Xu Jiang-Jiang , Gao Jie , Guo Jun-Hua , Song Li-Li
Published: October 2020

Background

Misuse and overuse of antibiotics by physicians in the treatment of children is common in China. This study aimed to reveal the overall use of antibiotics to treat children hospitalized in four types of pediatric wards.

Methods

Seven independent point prevalence surveys (PPSs) were conducted in Shanghai Children’s Hospital of Shanghai Jiao Tong University over the period 2012 to 2018. Pediatric ward types were defined general pediatric medical, pediatric surgical, pediatric intensive care units (PICU), and neonatal.

Results

A total of 3975 pediatric patients were included in the study, of which 63.9% received at least one dose antibiotic. The top five classes of antibiotics administered were cephalosporins (43.8%, n = 1743), penicillins (13.2%, n = 526), carbapenems (8.7%, n = 347), nitroimidazoles (7.1%, n = 281) and macrolides (6.5%, n = 257). The five most commonly used generic antibiotics were cefuroxime (14.9%, n = 594), ceftriaxone (9.7%, n = 387), cefotaxime (9.0%, n = 358), meropenem (8.1%, n = 320) and ampicillin/sulbactam (6.0%, n = 239). Meropenem was among top five antibiotics prescribed in the general pediatric, PICU and neonatal wards and sixth in the pediatric surgical wards. Of all children on antibiotics, 23.4% received prophylactic treatment, and prophylaxis accounted for 68.1% of indications for treatment in the pediatric surgical wards.

Conclusions

Given that over-treatment with third-generation cephalosporins and carbapenems has been associated with treatment-resistant infections, the prescription of these drugs should be strictly controlled and monitored, and measures should be taken to improve the management of surgical prophylaxis in hospitalized children in China.
The translation and validation of the Arabic Version of the Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (AR-PCOSQ)
Authors: Alghadeer Sultan , Algarawi Alhanouf , Abu-Rkybah Faten , Alshebly Mashael M. , Alruthia Yazed
Published: October 2020

Background

Polycystic ovarian syndrome (PCOS) is a hormonal disorder that is prevalent in females of reproductive age with signs and symptoms that significantly reduce self-esteem and have a negative impact on their quality of life. The management of PCOS signs and symptoms should result in an improvement in the health-related quality of life (HRQoL) of patients. Polycystic ovarian syndrome questionnaire (PCOSQ) is a disease-specific scale. The PCOSQ has been translated into different languages and assessed in different populations. The validity and reliability of PCOSQ varied depending on the ethnicity and culture of the respondents. The objective of the study was to establish a valid and reliable version of the PCOSQ (AR-PCOSQ) in Arabic.

Methods

A cross-sectional study using the translated and validated AR-PCOSQ questionnaire was conducted by interviewing 117 women with PCOS.

Results

The mean age (years) and BMI (kg/m2) of subjects were 29.90 ± 6.33 and 27.21 ± 5.54, respectively. Most of the patients had ≥ 1-year long history of PCOS (73.5%) and a post-school degree (64.96%). The content validity index (CVI) for the AR-PCOSQ from 10 gynecologists was 0.9, indicating satisfactory validity content. The internal consistency for reliability confirmation measured by Cronbach’s alpha coefficient was applied. Alpha coefficients for all items together was 0.863, indicating good reliability. The intraclass correlation coefficients for each item for 30 participants were also acceptable, ranging from 0.911 to 0.986 with p value < 0.001. As far as the factor analysis is concerned, the overall Kaiser–Meyer–Olkin sampling adequacy measure was 0.772. The Bartlett sphericity test was significant (p ≤ 0.001), Indicating that there were interrelated variables.

Conclusion

Our results demonstrated the initial reliability and validity of the Arabic version of the PCOSQ as a measure of specific HRQoL in Saudi women with PCOS. This will fill an important gap in measuring the HRQoL for patients with PCOS in research and community settings in Saudi Arabia. The AR-PCOSQ can be used to help prioritize health-related concerns from the patient’s perspective.
Accessing health services in India: experiences of seasonal migrants returning to Nepal
Authors: Adhikary Pratik , Aryal Nirmal , Dhungana Raja Ram , KC Radheshyam Krishna , Regmi Pramod R. , Wickramage Kolitha Prabhash , Duigan Patrick , Inkochasan Montira , Sharma Guna Nidhi , Devkota Bikash , van Teijlingen Edwin , Simkhada Padam
Published: October 2020

Background

Migration to India is a common livelihood strategy for poor people in remote Western Nepal. To date, little research has explored the degree and nature of healthcare access among Nepali migrant workers in India. This study explores the experiences of returnee Nepali migrants with regard to accessing healthcare and the perspectives of stakeholders in the government, support organizations, and health providers working with migrant workers in India.

Methods

Six focus group discussions (FGDs) and 12 in-depth interviews with returnee migrants were conducted by trained moderators in six districts in Western Nepal in late 2017. A further 12 stakeholders working in the health and education sector were also interviewed. With the consent of the participants, FGDs and interviews were audio-recorded. They were then transcribed and translated into English and the data were analysed thematically.

Results

The interviewed returnee migrants worked in 15 of India’s 29 states, most as daily-wage labourers. Most were from among the lowest castes so called-Dalits. Most migrants had had difficulty accessing healthcare services in India. The major barriers to access were the lack of insurance, low wages, not having an Indian identification card tied to individual biometrics so called: Aadhaarcard. Other barriers were unsupportive employers, discrimination at healthcare facilities and limited information about the locations of healthcare services.

Conclusions

Nepali migrants experience difficulties in accessing healthcare in India. Partnerships between the Nepali and Indian governments, migrant support organizations and relevant stakeholders such as healthcare providers, government agencies and employers should be strengthened so that this vulnerable population can access the healthcare they are entitled to.
Mutations in normal tissues—some diagnostic and clinical implications
Authors: Fiala Clare , Diamandis Eleftherios P.
Published: October 2020

Background

It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management.

Main body

The prevailing cancer development hypothesis posits that cancer originates from mutations in cancer-driving genes that accumulate in tissues over time. These mutations then confer special characteristics to cancer cells, known as the hallmarks of cancer. Mutations in specific driver genes can lead to the formation of cancerous subclones and mutation risk increases with age. New research has revealed an unexpectedly large number of mutations in normal tissues; these findings could have significant implications to the understanding of the pathobiology of cancer and for disease diagnosis and therapy. Here, we discuss how the prevalence of mutations in normal tissues provides novel and relevant insights about clonal development in cancer and other diseases. Specifically, this review will focus on discussing mutations in normal tissues in the context of developing specific, circulating tumor DNA (ctDNA) tests for cancer, and evaluating clonal hematopoiesis as a predictor of blood cancers and cardiovascular pathology, as well as their implications to the phenomena of neural mosaicism in the context of Alzheimer’s disease.

Conclusions

In view of these new findings, the fundamental differences between the accumulation of genetic alterations in healthy, aging tissues compared to cancer and cardiovascular or neural diseases will need to be better delineated in the future.
Assessment of Campylobacter fetus subsp. venerealis molecular diagnosis using clinical samples of bulls
Authors: Silva Marta Filipa , Duarte Ana , Pereira Gonçalo , Mateus Luísa , Lopes-da-Costa Luís , Silva Elisabete
Published: October 2020

Background

Campylobacter fetus subsp. venerealis (Cfv) is the pathogen responsible for Bovine Genital Campylobacteriosis (BGC), a venereal disease of cattle associated with impaired reproductive performance. Although several PCR assays were developed to identify this pathogen, most of them are still poorly evaluated in clinical samples. This study evaluated real-time PCR assays for Cfv detection in preputial samples of bulls (n = 308).

Results

The detection at the subspecies level (Cfv) compared four assays: two targeting ISCfe1 and two targeting parA gene. The detection at the species level (C. fetus) considered an assay targeting the nahE gene and a commercial kit for C. fetus identification. At the subspecies level, assays directed either to different targets (parA and ISCfe1), or to the same target (ISCfe1 or parA), showed a high percentage of disagreeing results. All samples positive at the subspecies level (n = 169) were negative in C. fetus detection assays, which strongly suggests the horizontal gene transfer of ISCfe1 and parA to other bacterial species. This was confirmed by microbiological isolation of three Campylobacter portucalensis strains responsible for false positive results. Sequences with a high level of identity with ISCfe1 and parA gene of Cfv were identified in C. portucalensis genome.

Conclusions

Overall, this study reveals that PCR assays solely directed to a subspecies target originate a high rate of false positive results, due to the presence of parA and ISCfe1 homologous sequences in other bacterial species, namely of the genus Campylobacter. Although the specificity of these methods may be higher if applied to bulls from herds with clinical features of BGC or in other geographical regions, current PCR diagnosis should couple subspecies and species targets, and further research must be envisaged to identify Cfv specific molecular targets.
Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion
Authors: Zhang Hai , Li Changhui , Hu Fang , Zhang Xueyan , Shen Yinchen , Chen Yuqing , Li Feng
Published: October 2020

Background

Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio.

Patients and method

The study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators.

Result

In the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (allp < 0.001). In the test set, PF CEA at the cut-off value of 5.23 ng/ml showed the highest sensitivity, specificity and accuracy, positive and negative predictive value among other tumor biomarkers, which were 99.0%, 69.1%, 91.6%, 90.7%, and 95.9%, respectively.

Conclusion

PF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.
Molecular interaction and cellular studies on combination photodynamic therapy with rutoside for melanoma A375 cancer cells: an in vitro study
Authors: Khorsandi Khatereh , Hosseinzadeh Reza , Chamani Elham
Published: October 2020

Background

Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells.

Methods

For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured.

Results

The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside.

Conclusion

The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.
YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer
Authors: Li Jiangfeng , Xie Haiyun , Ying Yufan , Chen Hong , Yan Huaqing , He Liujia , Xu Mingjie , Xu Xin , Liang Zhen , Liu Ben , Wang Xiao , Zheng Xiangyi , Xie Liping
Published: October 2020

Background

N6-methyladenosine (m6A) is the most abundant modification in mRNA of humans. Emerging evidence has supported the fact that m6A is comprehensively involved in various diseases especially cancers. As a crucial reader, YTHDF2 usually mediates the degradation of m6A-modified mRNAs in m6A-dependent way. However, the function and mechanisms of m6A especially YTHDF2 in prostate cancer (PCa) still remain elusive.

Methods

To investigate the functions and mechanisms of YTHDF2 in PCa, in vitro, in vivo biofunctional assays and epigenetics experiments were performed. Endogenous expression silencing of YTHDF2 and METTL3 was established with lentivirus-based shRNA technique. Colony formation, flow cytometry and trans-well assays were performed for cell function identifications. Subcutaneous xenografts and metastatic mice models were combined with in vivo imaging system to investigate the phenotypes when knocking down YTHDF2 and METTL3. m6A RNA immunoprecipitation (MeRIP) sequencing, mRNA sequencing, RIP-RT-qPCR and bioinformatics analysis were mainly used to screen and validate the direct common targets of YTHDF2 and METTL3. In addition, TCGA database was also used to analyze the expression pattern of YTHDF2, METTL3 and the common target LHPP in PCa, and their correlation with clinical prognosis.

Results

The upregulated YTHDF2 and METTL3 in PCa predicted a worse overall survival rate. Knocking down YTHDF2 or METTL3 markedly inhibited the proliferation and migration of PCa in vivo and in vitro. LHPP and NKX3–1 were identified as the direct targets of both YTHDF2 and METTL3. YTHDF2 directly bound to the m6A modification sites of LHPP and NKX3–1 to mediate the mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3–1 at both mRNA and protein level with inhibited phosphorylated AKT. Overexpression of LHPP and NKX3–1 presented the consistent phenotypes and AKT phosphorylation inhibition with knock-down of YTHDF2 or METTL3. Phosphorylated AKT was consequently confirmed as the downstream of METTL3/YTHDF2/LHPP/NKX3–1 to induce tumor proliferation and migration.

Conclusion

We propose a novel regulatory mechanism in which YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3–1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer. We hope our findings may provide new concepts of PCa biology.
Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm
Authors: Jahani Mozhgan , Dokaneheifard Sadat , Mansouri Kamran
Published: October 2020

COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.
A nomogram based on pretreatment CT radiomics features for predicting complete response to chemoradiotherapy in patients with esophageal squamous cell cancer
Authors: Luo He-San , Huang Shao-Fu , Xu Hong-Yao , Li Xu-Yuan , Wu Sheng-Xi , Wu De-Hua
Published: October 2020

Purpose

To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features.

Methods

Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions.

Results

A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95% CI 0.742–0.869, p < 0.001) in the training set and 0.744 (95% CI 0.632–0.851, p = 0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with p values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95% CI 0.779–0.897) in the training set and 0.807 (95% CI 0.691–0.894) in the validation set. Delong test showed that the nomogram model was significantly superior to the clinical staging, with p < 0.001 in the training set and p = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%.

Conclusion

We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.
Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy
Authors: Vrankar Martina , Kern Izidor , Stanic Karmen
Published: October 2020

Background

Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC.

Methods

National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining.

Results

Eighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005).

Conclusions

In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.
Is cup positioning easier in DDH patients previously treated with Bernese periacetabular osteotomy?
Authors: Ma Yunqing , Luo Dianzhong , Cheng Hui , Xiao Kai , Chai Wei , Li Rui , Zhang Hong
Published: October 2020

Background

Acetabular orientation changes after periacetabular osteotomy (PAO) lead to technical change when performing subsequent total hip arthroplasty (THA). There is no unified consensus regarding the solution for acetabular component installation after PAO. In the current study, we performed computed tomography (CT)-based simulation of acetabular component installation and compared the acetabular defect and component position following THA after PAO and the same patient before PAO.

Methods

From January 2014 to December 2018, pelvic models of 28 patients (28 hips) underwent PAO and with the risk factors to develop secondary osteoarthritis. The acetabular reconstruction process was simulated using 3D models from CT data, and the acetabular component coverage was calculated in 3D space based on the measurement and algorithm we proposed. We evaluated the anterior, posterior, superior, inferior acetabular sector angle (ASA), the medial wall thickness (MWT), and the distance from the hip center to the plane of pubic symphysis and ossa sedentarium in the study group (post-PAO group) and control group (pre-PAO group). In addition, we investigated the changes in the acetabular component covering and size between the two groups.

Results

A-ASA and I-ASA values were significantly smaller in the post-PAO group than in the pre-PAO group. The S-ASA and distance values were significantly bigger in the post-PAO group. Compared to the pre-PAO group, the post-PAO group has a bone defect in the anterior and inferior medial. However, the post-PAO group has to elevate the cup to improved component coverings.

Conclusion

Acetabular defection following simulation of cup installation after PAO was significantly changed compared to those without PAO. Elevation of hip joint centers as much as 4 mm and increase acetabular cup anteversion were therapeutic options for DDH patients following THA after PAO