bluuebunny/crossref_metadata_2025 huggingface dataset:
O4 Neural network image capture to predict response of oesophageal adenocarcinoma to neoadjuvant therapy
Authors: Rahman S , Early J , Sharpe B , Lloyd M , Grace B , De Vries M , Ramchurn S , Underwood T J
Published: July 2021

Introduction

Locally advanced oesophageal adenocarcinoma is typically treated with neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) followed by surgery. Significant benefit to neoadjuvant treatment however is confined to a minority of patients (<25%) and there are no reliable means of establishing prior to treatment in whom this benefit will occur. In this study, we assessed the utility of features extracted from high-resolution digital microscopy of pre-treatment biopsies in predicting response to neoadjuvant therapy in a machine-learning based modelling framework.

Method

A total of 102 cases were included in the study. Pre-treatment clinical information, including TNM staging, was obtained, along with diagnostic biopsies. Diagnostic biopsies were converted into high-resolution whole slide-images and features extracted using a pre-trained convolutional neural network (Xception). Elastic net regression models were then trained and validated with bootstrapping with 1000 resampled datasets. The response was considered according to Mandard tumour regression grade (TRG).

Result

There were 45 (44.1%) responders (TRG1-2) and 57 (57%) non-responders (TRG3-5) in the dataset. 34 patients (33.3%) received NACT and 68 (66.7%) received NACRT. A model trained with RNA-seq data achieved fair performance only in predicting response (AUC 0.598 95% CI 0.593–0.603), which was far exceeded by use of segmented diagnostic biopsy images (AUC 0.872 95% CI 0.869–0.875), which also produced well calibrated predictions of risk.

Conclusion

Despite using a small dataset, impressive performance in classifying response to neoadjuvant treatment can be achieved, particularly using automated image classification. Further study to refine the methodology is required before expansion to clinical settings.

Take-home Message

Response to neoadjuvant treatment for oesophageal cancer can be predicted from diagnostic biopsies
O6 Analysis of angiogenic gene profiling after E-selectin + stem cell therapy in murine ischemic limb
Authors: Quiroz Hallie J , Shao Hongwei J , Li Yan , Ortiz Yulexi Y , Parikh Punam P , Lassance-Soares Roberta M , Liu Zhao-Jun J , Velazquez Omaida C
Published: July 2021

Introduction

There remains a paucity of novel therapeutics for limb salvage in patients with critical limb ischemia (CLI) for whom revascularization procedures have failed and amputation is imminent. We have shown that E-selectin+/Mesenchymal Stem Cell (MSC) injections into the ischemic limb tissue of a CLI mouse model improves revascularization and limb function. Thus, we sought to determine a mechanism of action for E-selectin+/MSC’s pro-angiogenic and tissue salvage properties.

Methods

MSC were extracted from donor mice bone marrow and subsequently engineered via viral transduction with E-selectin-ires-GFP/AAV and GFP/AAV (control) to create E-selectin-GFP+/MSC vs GFP+/MSC. Intramuscular injections of E-selectin-GFP+/MSC, GFP+/MSC, or PBS were performed in a mouse model of hindlimb ischemia. Laser doppler imaging (LDI), confocal laser microscopy, and treadmill exhaustion test were utilized to determine neovascularization and limb function. RNA extraction from engineered MSC (E-selectin-GFP+/MSC vs GFP+/MSC) and ischemic hindlimb tissues treated with E-selectin-GFP+/MSC vs GFP+/MSC was performed, followed by RT2 Profiler PCR Array analysis of 84 genes involved in angiogenesis. GFP+/MSC treated hindlimb tissue served as control. Student’s t-test or ANOVA was utilized to compare means and significance set at P < 0.05.

Results

Compared with GFP+/MSC and PBS, treatment with E-selectin-GFP+/MSC increased ischemic leg LDI reperfusion (54% vs. 39% vs. 22%, P < 0.001), treadmill distance traversed (162 m vs. 111 m vs. 110 m, P < 0.01) and ischemic mouse footpad vessel density (23% vs. 14% vs. 14%, P < 0.01). RT2 Profiler PCR Array demonstrated pro-angiogenic gene upregulation occurred in 7 genes (Csf3, Cxcl2, Cxcl5, Serpine1, F2, Lep, Tbx1, Table I.) in E-selectin-GFP+/MSC treated ischemic leg tissue while tumour necrosis factor (TNF) was found to be downregulated, when compared with GFP+/MSC treated tissues. Of these 7 upregulated genes, CXCl2, F2, Leptin and T-box1 (Table I.) are likely produced by E-selectin-GFP+/MSC, as analysis of cellular gene expression profiles of E-selectin-GFP+/MSC also revealed upregulation by 2-fold or more in these factors when compared to GFP+/MSC. Validation of gene functions in-vivo are under investigation.

Conclusion

Stem cell therapy using E-selectin-GFP+/MSC, in a murine model of CLI, confers both augmented postnatal neovascularization and increased limb function. The pro-angiogenic and pro-repair effects are likely mediated by upregulation of a panel of chemokines/cytokines and down-regulation of TNF in ischemic tissues treated with E-selectin-GFP+/MSC.
O11 Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an important clinical and prognostic indicator in pancreatic cancer
Authors: Yang Y M , Sanders A J , Dong X , Cui Y , Hao C , Ji J , Jiang W G
Published: July 2021

Introduction

Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a cell adhesion molecule and one of the potential metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cell adhesion. The present study investigated the clinical, pathological and prognostic value of ALCAM in patients with pancreatic cancer.

Method

Pancreatic cancer tissues (n = 223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts. The expression was analysed against clinical, pathological and clinical outcome of the patients. We validated our findings with an available TCGA database (n = 117), including correlations with the ALCAM interactive partners.

Result

Pancreatic cancer tissues had significantly higher levels of ALCAM transcript than normal tissues (P < 0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P = 0.018), finding also supported by ROC analysis (P = 0.016). Multivariant analysis showed ALCAM as an independent prognosis factor for overall survival (hazardous ratio 5.485), with both nodal status and TNM staging contributing to the model (HR 2.578 and 3.02 respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P = 0.021, with vs without tumour embolism). ALCAM significantly correlated with its interactive protein partners including CD6 and ITGB1, but not L1CAM.

Conclusion

ALCAM/CD166 expression is aberrant in pancreatic cancer and the raised expression is an independent prognostic factor for the survival of the patients and the microvessel embolism by cancer cells.

Take-home Message

ALCAM is a prognostic indicator for survival and tumour embolism in pancreatic cancer
O13 Acid ceramidase: a potential biomarker for locally advanced rectal cancer?
Authors: Clifford Rachael Elizabeth , Govindarajah Naren , Bowden David , Sutton Paul , Parsons Jason , Vimalachandran Dale
Published: July 2021

Introduction

We have previously utilized proteomic and immuno-histochemical data to validate that high levels of acid ceramidase (AC) expression confers poorer neoadjuvant response in rectal cancer. Biological (siRNA, plasmid and CRISPR) AC manipulation altered radiosensitivity in-vitro. We aimed to assess the radiosensitising effect of pharmacological AC inhibitions and elucidate the potential underlying mechanism.

Methods

Optimal drug dosing was achieved using ELISA activity assays in multiple colorectal cancer cell lines (HCT116, HT29, LIM1215). Carmofur and a novel small molecular inhibitor (LCL521) were used as pharmacological inhibitors. Standard clonogenic assays assessed cell survival following increasing irradiation (2 D), volume change in 3 D spheroids and cell viability in patient derived organoids. Annexin V/PI staining was used to determine apoptosis.

Results

Carmofur clonogenic assays demonstrated reduced colony formation efficiency (CFE) and improved radiosensitivity across cell lines. HCT116 showed 0.438(CFE) control v 0.183(CFE) carmofur at 1 Gy, 0.140(CFE) control v 0.076(CFE) at 2 Gy (P = 0.000563). LCL521 dosing improved radiosensitivity in spheroid models. HCT116 volume day-15 2.36x10-5mm v control 4.15x10-5mm. siRNA-AC demonstrated increased apoptosis across time points compared to NT control (P = 0.035), and increased poly-ADP ribose polymerase-1 (PARP-1) cleavage in a p53-dependent process.

Conclusion

Initial work demonstrates that pharmacological inhibition of AC produces comparative radiosensitizing effects in these cell lines and cancer models. siRNA-AC increases apoptosis, suggestive of a potential underlying mechanism. This work further solidifies AC as a potential biomarker, however further recapitulation in more complex models and ultimately in-vivo is required to establish a translatable clinical role.
O14 Optimising the management of primary breast cancer in older women
Authors: Parks R M , Green A R , Cheung K L
Published: July 2021

Introduction

The risk of breast cancer increases with age and our global population is ageing. By 2040 the number of breast cancer cases diagnosed per year worldwide will double and over 40% of these will be in patients aged 70 or over. Despite this, there are few treatment guidelines specific to breast cancer in older women and none which consider the unique biological differences of this cohort.

Method

Surgical and core needle biopsy (CNB) specimens were obtained from an existing series of 1,785 women over the age of 70 with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and 693 CNB specimens. Immunohistochemical staining for 32 biomarkers has been performed in all of the available TMAs. Association between histological score for each biomarker and tumour size, grade, recurrence rate, breast cancer specific and overall survival is currently being investigated in the whole cohort.

Results

Results to date have revealed a unique biological cluster in older women with primary breast cancer that is not seen in a comparative younger cohort. In the future, bioinformatics analysis will determine which biomarkers and in what combination, can predict chance of recurrence/overall survival in this cohort.

Conclusions

This information will be used to create a prognostic tool specific to assist older women with decision making regarding primary treatment of breast cancer.
O15 Venous Leg Ulceration: an assessment of associated lifestyle, sociodemographic and clinical factors using UK Biobank
Authors: Salim Safa , Vidal-Diez Alberto , Machin Matthew , Patterson Benjamin O , Onida Sarah , Davies Alun H
Published: July 2021

Introduction

A number of factors have reportedly been associated with venous leg ulceration (VLU) however many of these remain disputed. UK Biobank (UKB) is an electronic dataset that provides in-depth detail on the lives of its participants. The aim of this research is to utilise UKB to understand factors associated with VLU.

Methods

Participants in the UKB with historical or active venous ulceration were identified and an age, sex and comorbidity matched control group was formed. A multivariate logistic regression was used to explore factors associated with VLU with significant factors expressed through odds ratios (OR). Mortality was investigated using a Kaplan Meier plot and log-rank test. Data analysis was preformed using R Studio Version 1.2.5033 and Python 3.8.10.

Results

Factors associated with VLU included; male gender, older age, deprivation (OR 1.27), obesity (OR 1.40), current smoking (OR 1.21), immoderate alcohol intake (OR 1.32), previous deep vein thrombosis (OR 3.07), depression and loneliness (OR 1.21). Biochemical factors associated with VLU included low haemoglobin concentrations (OR 1.50), low circulating lymphocyte percentages (OR 1.57), raised glycated haemoglobin (HbA1c) (OR 2.92), raised c-reactive protein (OR 1.41), raised cystatin C (OR 1.11) and low Vitamin D levels (OR 1.52). At a median follow up of 11.5 years, the mortality in VLU participants was 28%; significantly higher than in controls (P < 0.001).

Conclusion

Participants with VLU are comorbid with poorer physical, social and psychological wellbeing.
O23 Outcomes after non-operative management of perforated diverticular disease: a population based cohort study
Authors: Adiamah A , Ban L , Otete H , Crooks C J , West J , Humes D J
Published: July 2021

Introduction

The management of perforated diverticular disease has changed in the last 10 years with a move towards less surgical intervention. This population based cohort study aimed to define the risk of mortality and readmission following non-operative management of perforated diverticular disease (DD).

Method

Patients diagnosed with perforated DD and managed without surgery were identified from the linked Clinical Practice Research Datalink and Hospital Episode Statistics data from 2000 to 2013. The outcomes were 1-year case-fatality, re-admissions and surgery at re-admission.

Result

In total, 880 patients with perforated DD were managed without surgery, comprising of 523 females (59.4%). One year case-fatality was 33.2% (293/880). The majority of deaths occurred in the first 90 days following the index admission with a 90 day case-fatality of 28.8%. 90 day survival varied by age with 97.2% survival at 90 days in those under 65 years compared to 85.0% in those between 65–74 years and 51.5% in those over 75 years.

Of 767 patients discharged from hospital, 250 (32.6%, 250/767) were re-admitted (47 elective(6.1%) and 203 emergency(26.5%)) during a median of 1.6 years of follow-up (iqr 0.1–3.9 years) with similar proportions in each age category. In the first year of follow-up only 5.1% of patients required surgery of whom 16/767 (2.1%) required elective and 23/767 (3.0%) emergency surgery.

Conclusion

Conservative management of perforated diverticulitis in those under 65 years is feasible and safe. A third of patients are readmitted during follow-up, however, re-intervention rates following conservative management were low across all age categories.

Take-home Message

In younger patients (<65yrs) conservative management of perforated diverticulitis is feasible and safe. A third of conservatively managed patients are readmitted during follow-up, however, need for surgery on readmission is rare.
O37 Carotid surgery during the COVID-19 pandemic
Authors: Busuttil A , Jacob L , Elanwar S , Lim C. S , Baker D. M
Published: July 2021

Introduction

The aim of this prospective study was to evaluate the efficacy and safety of carotid endarterectomy for symptomatic carotid stenosis during the COVID-19 pandemic.

Method

Re-organisation of stroke services due to the COVID-19 pandemic resulted in carotid endarterectomy for symptomatic disease being performed in two hospitals; Covid-19 free and non-free sites. Patients were referred from multiple online regional neurovascular multi-disciplinary team meetings, and managed according to the pre-Covid-19 guidance. All patients referred for carotid endarterectomy between 23 March 2020 and 31 July 2020 were included. Demographic, medical history, imaging, peri-operative, complication and follow-up data were collected and analysed prospectively.

Result

28 patients were referred for carotid endarterectomy, of whom 21 patients underwent surgery. The mean time to surgery was 11 days (3–35). The technical success rate was 100%. Peri-operatively and within 30-days post-operatively, no patient suffered death or stroke. There were 2 minor complications; one non-ST elevation myocardial infarction, and another wound haematoma and infection requiring readmission for antibiotics. No patient developed new COVID-19 infection post-operatively. Of the 7 patients not operated on; 2 were medically unfit for surgery, three declined surgery, and two had free floating thrombus that was managed successfully with anti-coagulation.

Conclusion

During the pandemic, the provision of carotid endarterectomy for symptomatic carotid diseases was carried out safely and within the current recommendations, with several pre-cautionary measures being undertaken. Therefore, symptomatic carotid intervention should still be considered to reduce the risk of stroke provided similar pre-cautionary measures are undertaken.

Take-home Message

Carotid surgery should continue during successive waves of the COVID-19 pandemic
O39 Unidimensional and functional pain assessment tools in postoperative adult patients: a systematic review of their development and utility
Authors: Baamer R M , Iqbal A , Lobo D N , Knaggs R D , Levy N A , Toh L S
Published: July 2021

Introduction

The Visual Analogue Scale (VAS), Numeric Rating Scale (NRS), Verbal descriptor scale, and faces pain scale are used to measure postoperative pain in adults. However, their utility in this population has not been reviewed systematically. We aimed to summarise and appraise the evidence relating to the measurement properties of unidimensional tools when used for this population and to identify available tools assessing the impact of pain on the restoration of function.

Method

Four databases (MEDLINE, EMBASE, CINAHL, PsycINFO) were searched up to August 2020 for relevant studies. Two reviewers independently screened articles and assessed risk of bias using the COensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist.

Result

Thirty-one studies were included. Only one study included an objective pain score; a tool assessing pain interference with function and reported low-quality evidence for construct validity. Studies looked at unidimensional tools were underpinned by low or very low-quality evidence for reliability, and all displayed a low quality of evidence of indeterminate responsiveness. Measurement error was only reported for VAS in one study of moderate quality. Interpretability results were available only for VAS and NRS. Feasibility results varied based on the included population.

Conclusion

Despite the extensive use of unidimensional tools, there is no evidence to suggest that any of these tools has superior measurement properties for postoperative pain. Therefore, future studies should be prioritised to assess their validity, measurement error and responsiveness. Validation studies of pain assessment tools that promote function are needed.

Take-home Message

Take home message: Functional pain scores should be assessed and validated for postoperative pain.
Epidemiology and burden of chronic kidney disease-associated pruritus
Authors: Kim Dana , Pollock Carol
Published: August 2021

Chronic kidney disease–associated pruritus (CKD-aP) is a common, yet underrecognized condition in patients with CKD and end-stage kidney disease (ESKD). Real-world observational studies indicate that CKD-aP affects up to 80% of ESKD patients undergoing haemodialysis (HD), with ∼40% experiencing moderate to severe itch. CKD-aP can negatively impact patients’ mental and physical health-related quality of life (HRQoL) and is also associated with sleep disturbance and depression. Several studies have found that CKD-aP is a predictor of adverse medical outcomes, including an increased risk of hospitalizations and mortality. In this article we review the literature relating to the epidemiology of CKD-aP to describe its prevalence across the treatment spectrum of CKD (non-dialysis, HD, peritoneal dialysis and transplant recipients) and to summarize potential risk factors associated with its development. We also review key data from studies that have evaluated the impact of CKD-aP on HRQoL and medical outcomes.
Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis
Authors: Witkowski Marco , Witkowski Mario , Friebel Julian , Buffa Jennifer A , Li Xinmin S , Wang Zeneng , Sangwan Naseer , Li Lin , DiDonato Joseph A , Tizian Caroline , Haghikia Arash , Kirchhofer Daniel , Mach François , Räber Lorenz , Matter Christian M , Tang W H Wilson , Landmesser Ulf , Lüscher Thomas F , Rauch Ursula , Hazen Stanley L
Published: August 2021

Aims

Gut microbiota and their generated metabolites impact the host vascular phenotype. The metaorganismal metabolite trimethylamine N-oxide (TMAO) is both associated with adverse clinical thromboembolic events, and enhances platelet responsiveness in subjects. The impact of TMAO on vascular Tissue Factor (TF) in vivo is unknown. Here, we explore whether TMAO-enhanced thrombosis potential extends beyond TMAO effects on platelets, and is linked to TF. We also further explore the links between gut microbiota and vascular endothelial TF expression in vivo.

Methods and results

In initial exploratory clinical studies, we observed that among sequential stable subjects (n = 2989) on anti-platelet therapy undergoing elective diagnostic cardiovascular evaluation at a single-site referral centre, TMAO levels were associated with an increased incident (3 years) risk for major adverse cardiovascular events (MACE) (myocardial infarction, stroke, or death) [4th quartile (Q4) vs. Q1 adjusted hazard ratio (HR) 95% confidence interval (95% CI), 1.73 (1.25–2.38)]. Similar results were observed within subjects on aspirin mono-therapy during follow-up [adjusted HR (95% CI) 1.75 (1.25–2.44), n = 2793]. Leveraging access to a second higher risk cohort with previously reported TMAO data and monitoring of anti-platelet medication use, we also observed a strong association between TMAO and incident (1 year) MACE risk in the multi-site Swiss Acute Coronary Syndromes Cohort, focusing on the subset (n = 1469) on chronic dual anti-platelet therapy during follow-up [adjusted HR (95% CI) 1.70 (1.08–2.69)]. These collective clinical data suggest that the thrombosis-associated effects of TMAO may be mediated by cells/factors that are not inhibited by anti-platelet therapy. To test this, we first observed in human microvascular endothelial cells that TMAO dose-dependently induced expression of TF and vascular cell adhesion molecule (VCAM)1. In mouse studies, we observed that TMAO-enhanced aortic TF and VCAM1 mRNA and protein expression, which upon immunolocalization studies, was shown to co-localize with vascular endothelial cells. Finally, in arterial injury mouse models, TMAO-dependent enhancement of in vivo TF expression and thrombogenicity were abrogated by either a TF-inhibitory antibody or a mechanism-based microbial choline TMA-lyase inhibitor (fluoromethylcholine).

Conclusion

Endothelial TF contributes to TMAO-related arterial thrombosis potential, and can be specifically blocked by targeted non-lethal inhibition of gut microbial choline TMA-lyase.
Identification of nurse work safety measures used in emergency service during pandemic in the state of Goiás, Brazil
Authors: Faria Everson , Arão Isabelle , Simões Helder , Vidal Diogo
Published: August 2021

Background

Due to the Nurses performance in the front line to combat COVID-19 pandemic in Brazil, the exposure of these healthcare professionals has become a health and safety problem in the professional sphere. The objective of the present work was to identify the existing safety measures to protect the nursing team in the Health System.

Methods

A survey was conducted in October 2020 through an online platform to 89 professionals nurses working in municipalities in the state of Goiás, Brazil, on the front lines in the fight against COVID-19.

Results

83.1% reported that they received training to deal with the pandemic. 68.2% of the participants do not have the right to use the refusal of activity in the face of a situation that jeopardized their health. The majority of the sample (56.2%) claimed to have had no psychological support, have worked under pressure (62.9%) and have contact with an infected patient (89.9%). The results identified several safety measures implemented to protect the nursing team: training, distribution, use and control of Individual protection equipment PPE; existence of a prevention commission, security dialogue meetings; informational communication about the pandemic and the existence of a cleaning and hygiene team.

Conclusions

The research concluded that there is still a lack of adherence to various safety measures in daily activities, once isolated measures do not minimize exposure and/or contagion. Despite collective measures being not enough to protect the nursing team, they are the most recommended at the current state of knowledge.
Association between psychosocial risks and performance of radiology technicians in emergency context: outcomes of a cross-section study
Authors: Paiva Inês , Simões Helder , Matos Paulo , Duarte Elisabete , Figueiredo João Paulo , Vidal Diogo , Tavares Óscar
Published: August 2021

Background

The workers' demand, the introduction of new technologies and the increase in working hours are some of the main factors that result in the emergence of psychosocial risks. These risks compromise workers mental and physical health, and the well-being, leading to consequences not only at the individual level but also at the organizational level. This work aims to determine the capacity of the radiology technicians to work, the psychosocial risks to which they may be exposed, as well as the possible influence of these on their professional performance.

Methods

The Work Ability Index (ICT) and the psychosocial risk scale identified as Copenhagen Psychosocial Questionnaire (COPSOQ) were applied in a sample of 29 professionals (urgency sector of the University Hospital of Coimbra, Portugal), from a universe of 36 radiology technicians.

Results

The ICT did not differ according to gender, age and qualification among the professionals under study. However, single technicians presented better ICT compared to the other groups. Radiology technicians with a bachelor's degree were more exposed to psychosocial risks in terms of job performance, transparency of the work role, professional rewards, justice and respect, as well as professional self-efficacy.

Conclusions

Studies on psychosocial risks have shown the importance of understanding how the former directly and indirectly influence the professional performance of workers, but also the need to develop strategies to prevent the same risks by improving working conditions and performance of the workers.
Impact of COVID-19 lockdown in psychological well-being among students in polytechnic of Santarem and Leiria
Authors: Gonzaga Luís , Silva Mário , Figueiredo Maria do Carmo , Rosa Marta , Matos Rui , Amendoeira José
Published: August 2021

Background

The social restraints during the COVID-19 mandatory lockdown led young and undergraduate adults living remarkable changes in their daily lives, challenging the feeling of loneliness and the own perception of social isolation. This study aimed to assess and compare the levels of psychological well-being among students from both Santarém and Leiria Polytechnic Institutes.

Methods

A descriptive cross-sectional correlational study was performed in the period immediately after the first lockdown. Participants were 775 students (females = 73.5%), aged between 17 and 55 years. All of them completed measures of the Psychological Well-Being Manifestation Scale (PWBMS; or EMMBEP, in the Portuguese version, by Monteiro, Tavares e Pereira, 2012) measuring six dimensions, components of the eudaimonic model of well-being. Collected data were analyzed with IBM SPSS Statistics for Windows software, Version 27.0.

Results

The results obtained revealed differences of quality in the scores of the six measured dimensions. If subjective experiences on Mental Balance and Sociability are the best indicators of the well-being, the perception of the lack of Social Involvement and low Happiness appear to be limitative factors to the perceived well-being. We also found significant differences in terms of polytechnic institute attended, gender, age categories, and marital status.

Conclusions

The obtained results provide the basis to design and develop a targeted intervention main program focused on the empowerment of higher education students. Build a literacy program with health education strategies, starting from their own perceptions and responses to the experienced situations, allows their easy engagement in the promotion of the psychological well-being.
Novel subgroups of adult-onset diabetes and their outcomes: relationship between previous cardiovascular events and microvascular complications
Authors: Santos Claudio , Brito-Costa Sonia , Margalho Luis , Monteiro Pedro
Published: August 2021

Background

Type 2 Diabetes Mellitus (T2DM) is a global scale problem, closely related to genetic and environmental factors, such as aging, family history, diet, lack of physical exercise, physical inactivity and obesity, which contribute to the increase in its prevalence.

Methods

191 participants (EG) with T2DM with the average of 70.3 years (SD = 8.3) and 36 with pre-diabetes (CG) with an average of 62 years (SD = 10.3) who participated in clinical trials at Clinical Research Unit in Cardiology of Coimbra Hospital and Universitary Centre without cognitive difficulties, were divided in 5 different clusters. These were established based on six different variables: body mass index (BMI), age of each individual, age at diagnosis of DMT2, glycated haemoglobin value (HbA1c), homeostatic model that estimates the function of β cells (HOMA2-B) and insulin resistance (HOMA2-IR).

Results

Cluster 1 presented pre-diabetic individuals (15.9%), while diabetic individuals were divided into clusters 2 (1.8%), 3 (17.6%), 4 (21.1%) and 5 (43.6%). Regarding the study of the prevalence of previous cardiovascular events, the majority of individuals present in the different clusters had history of acute myocardial infarction (AMI). For the prevalence of microvascular complications, only chronic kidney disease (CKD) was found in the vast majority of different groups. It was observed a dependency relationship between previous AMI and CKD in clusters 3 (P = 5.16E-5; P < 0.05), 4 (P = 0.0004; P < 0.05) and 5 (P = 0.0023; P < 0.05).

Conclusions

It was possible to create different clusters in a sample of the Portuguese population and to observe the existence of dependency relationships between different previous cardiovascular events and microvascular complications.
LDHA is differential expressed in luminal A and luminal B breast cancer
Authors: Vieira F Q , Cardoso A R , Gigliano D , Carneiro I , Henrique R , Jerónimo C , Silva R A
Published: August 2021

Background

Breast cancer (BrCa) is the most incident cancer in women worldwide, with more than 2 200 000 new cases and 600 000 deaths in 2020. Concerning BrCa molecular signature, tumors expressing estrogen receptor (luminal A and B) normally respond to hormonal therapy, but some cases develop resistance. We recently showed that LDHA expression is reduced upon treatment with [C16Pyr][Amp], a new proposed anti-cancer drug. LDHA has been implicated in Warburg effect regulation and has been associated with BrCa patients’ worse outcome. So, the mail goal of this study was to evaluate LDHA expression in BrCa tissues and correlate it with several clinical and pathological parameters.

Methods

A total of 40 BrCa tissue samples were selected to assess LDHA expression by immunohistochemistry. Percentage of positive tumor cells, intensity of immunostaining, and immunoexpression pattern were blinded evaluated. Correlations between clinicopathological parameters and LDHA expression were assessed using the Chi square test (P < 0.05 was indicated of the statistically significance).

Results

Higher LDHA expression intensity significantly is associated with luminal B molecular subtype (P = 0.003). Conversely, no association is found between LDHA expression and tumor stage or therapy resistance.

Conclusions

The intensity of LDHA immunoexpression is related with luminal molecular subtype B. Since LDHA is associated with the production of lactate, leading to a greater energy obtaining by cancer cells, these cells may have an increased capacity for proliferation. In fact, this subtype was previously reported to express high Ki67 levels, a proliferative marker.
Therapeutic potential of human neural precursor cells in diabetic retinopathy—preclinical model
Authors: Saçaki Claudia Sayuri , Mogharbel Bassam Felipe , Stricker Priscila Elias Ferreira , Dziedzic Dilcele Silva Moreira , Irioda Ana Carolina , Perussolo Maiara Carolina , Ferreira Fabiano Montiani , Moreno Juan , Dornbusch Peterson , Sato Mário , Shiokawa Naoye , de Noronha Lucia , Galdino Marianna Bacelar , Abdelwahid Eltyeb , Franco Célia Regina Cavichiolo , de Carvalho Katherine Athayde Teixeira
Published: August 2021

Background

Considering the expressive number of individuals being diagnosed with diabetes worldwide, it is relevant to find medicines and treatments, in order to achieve diabetes complications, as diabetic retinopathy (DR) long-awaited regression and/or cure. The study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) on induced diabetic retinopathy (DR) in Wistar rats.

Methods

Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres, then hNPCs were obtained and characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = 4; diabetic without treatment (DM) n = 9; diabetic with cell therapy (DM + hNPCs) n = 9. Cells were transplanted by intravitreal injection (1 x 106 cel/µL) into each of Streptozotocin (STZ) induced diabetes rats. Evaluations by Optical Coherence Tomography (OCT) and Electroretinography (ERG) were done before and after diabetes induction and post cell therapy. Four weeks after treatment, eye enucleation allowed histopathological and immunohistochemistry (IHC) analysis.

Results

hNPCs increased the number of retina ganglion cells, ameliorated the photoreceptor layer, and decreased the microvessel points, evidenced by ERG, OCT, histopathological, and IHC findings. The most relevant differences in morphological analysis (treated vs untreated), exhibit the retinal improvement in many layers, notably in the retinal pigment epithelium and photoreceptors.

Conclusions

hNPCs reduced DR progression, as demonstrated by a neuroprotective effect and promotion of retinal regeneration.
Vanadium compounds therapeutic effects in melanoma
Authors: Amante Cristina I , Aureliano Manuel , De Sousa-Coelho Ana Luísa
Published: August 2021

Background

Polyoxometalates are a diverse family of metal-oxo anions of early transitional metal ions in high oxidation states, including vanadium. Such compounds are gaining increasing interest in biomedicine due to their anti-cancer activity. Regarding melanoma, available therapies’ effectiveness is still currently limited, commonly leading to relapse. For this reason, it is vital to identify novel anti-cancer agents.

Methods

To better understand the mechanism of action involved in the anti-cancer vanadium-based compounds in melanoma, we conducted a systematic review. Search was performed in Clinical Trials, Cochrane Library, Pubmed, Scielo, and Web of Science (20/4-8/5/2020). Review articles were excluded. Inclusion criteria considered articles between 2000 and 2020, written in English, in which vanadium compounds were evaluated alone (not combined with other drugs), allowing to recognise the effects exclusively derived from vanadium.

Results

Based on the inclusion/exclusion criteria, a total of 5 articles, published between 2013 and 2020, were analyzed. All tested compounds, including Oxidovanadium(IV) complexes [VIVO(mpp)2] and [VIVO(ppp)2] (VS3, VS4), reduced cellular viability. Moreover, Vanadium pentoxide (V2O5) and Xyloglucan from Copaifera Langsdorffii complexed with Oxovanadium(IV/V) (XGC:VO), in murine B16F10 cells, and Inorganic anion vanadate (VN), [VIVO (dhp)2] (VS2), and N,N’-ethylenebis (pyridoxylideneiminato) vanadium(IV) complex [Pyr2enV(IV)], in A375 cells, induced apoptosis. VN, VS2 and Pyr2enV(IV) increased reactive oxygen species (ROS) levels in A375 cells. In vivo experiments demonstrated that V2O5 prolonged the life of mice implanted with B16F10 cells, with no systemic toxicity.

Conclusions

Several different vanadium-based compounds have anti-cancer potential in melanoma, mainly increasing apoptosis and ROS production. Specific metal-based complexes are potential melanoma treatments, which might have been previously neglected.
A comparative study on indirect costs of suicide in Portugal: productivity loss as an additional way to approach healthcare prioritization
Authors: Neto J , Carvalho C , Almeida P
Published: August 2021

Background

Suicide and voluntary self-harm (SVSA) accounted for 0.95% of all deaths in Portugal in 2017. Economic evaluation includes indirect costs analysis, relating to Years of Life Lost (YLL) and premature death. This study aimed to estimate and compare the indirect costs from loss of productivity due to SVSA and 12 other causes of death in 2017.

Methods

YLL were adapted to the working age (18–66 years-old) ‘Years of Productivity Lost’ (YPL) adjusting the groups 15–19 years-old and under, and disregarding the ages over 66 years-old. The causes of death were based on the European Shortlist. The loss of productivity from deaths was estimated from the YPL and the ‘Apparent Productivity of Work’, with an annual discount rate of 3%, translated into % of Gross Domestic Product (GDP) in 2017. The calculations were performed for the SVSA and for 12 causes of death selected from national Priority Health Programs. The INE and Pordata databases for the year 2017 were used. Calculations were performed using Microsoft Excel for Office 365 software version 2102.

Results

The estimated costs from loss of productivity by SLAV deaths in 2017 represented approximately 0.16% of GDP. It is the third highest among the 13 causes of death analyzed, ranking behind malignant neoplasm of larynx/trachea/bronchi/lung and ischaemic heart disease.

Conclusions

Prioritization of health resources may benefit by integrating lost productivity concepts with other indicators. Limitations include predictable increase of retirement age in the future and the oversimplified calculation of productivity costs. Future studies may include sensitivity assessments and other relevant variables.
Drug–drug interaction in elderly patients with cancer
Authors: Capitão Romana , Jesus Ângelo , Oliveira Rita , Afreixo Vera
Published: August 2021

Background

Elderly cancer patients have a high risk of exposure to potential drug-drug interactions (pDDIs), given the therapeutic complexity to which they are subjected. The study of pDDIs is very important to enable more effective treatments, with the least possible number of complications.The aim of this study was to identify and characterize pDDIs in elderly cancer patients treated at the Day Hospital of IPO-Porto.

Methods

Information about patients sociodemographic data and chronic medication were collected through an interview with application of a questionnaire to the elderly patient. Patient’s clinical files were also consulted to complement information needed for the study. The ATC classification of drugs was performed and Micromedex® tool was used to identify and characterize pDDIs. The most prevalent pDDIs were analyzed and discussed.

Results

A total of 335 elderly patients with cancer were enrolled in the study. The prevalence of polymedication was 88.10% and excessive polymedication was 46.60%. A total of 1125 pDDIs were identified in 248 patients (74.03%) and 211 pDDIs involved at least one antineoplastic drug. The pDDIs that were detected more frequently were: Fluorouracil - Leucovorin Calcium (N = 28), Cyclophosphamide - Ondansetron (N = 27) and Metoclopramide - Tramadol (N = 20). A significant association was detected between the number of drugs consumed and the number of pDDIs.

Conclusions

Elderly patients with cancer have a high risk of drug interactions, given the polymedication they are exposed. It's crucial to implement measures to monitor their therapy in order to reduce the potential for drug interactions and improve the quality of patient's life.
Body mass index, shift work and food consumption: what relationship?
Authors: Morgado Carolina , Lima João
Published: August 2021

Background

A significant percentage of the population is working on shift work and according to several studies this type of work schedule has been associated with an increased risk of developing some pathologies, such as obesity, which are one of the biggest mortality causes in the world. To understand if the shift work has a negative influence on the workers' diet and if it affects the Body Mass Index.

Methods

Observational and cross-sectional research was conducted, through an online survey designed for this purpose, including fruit and vegetables consumption, sociodemographic characteristics, shift work schedule, sleep hours and reported values of weight and height. The study was ethical approval and statistical analysis was performed using the IBM SPSS Statistics software. A critical significance level of 5% was considered.

Results

145 workers were evaluated with an average age of 35.90 ± 10.92 years and an average Body Mass Index of 25.12 ± 4.54 kg/m2, 76.6% were female. 51.7% of the individuals worked on shift work. Body Mass Index of shift workers is higher than Body Mass Index day shift workers (P = 0.001), and they sleep, on average, less hours than day workers. No differences was observed related to fruit and vegetables consumptions. Shift workers reported to have higher difficult to management food intake when compared with day workers (P < 0.001).

Conclusions

Shift work seems to have a negative influence on the workers' sleep and in Body Mass Index. This study is important to develop, in the future, individualized strategies, for these workers
Ergonomic risk assessment in medical-dental clinics
Authors: Ferreira Ana , Lança Ana , Figueiredo João Paulo , Seco Silvia , Loureiro António , Paixão Susana , Costa Lúcia Simões , Martins Mariana
Published: August 2021

Background

The ergonomic applied to Dental Medicine aims to develop an ergonomically planned environment, with equipment rationally distributed, to reduce physical and cognitive stress, prevent diseases related to professional exercise, increasing productivity, improving the quality of service provided and reducing fatigue in the working team. However, physical work usually imposes muscle tension on the musculoskeletal system that can culminate in work-related trauma, commonly called Musculoskeletal Disorder.

Methods

We proposed as an objective, to evaluate how the ergonomic risks in Medical-Dental Clinics, which can cause work-related Musculoskeletal Injuries, influence the quality of life and health of the workers.

The checklist was applied based on the legislation in force and, at the same time, a questionnaire was applied for consultation with the workers; identification of the tasks of all workers and their associated risks has been carried out; ergonomic studies of the workstations concerned have been carried out and, in the light of the results obtained, preventive measures have been indicated to address the problems.

Results

Through the Rula Method, we evaluated the level of performance in relation to the tasks performed and found that most of these corresponded to level 3, which corresponded to values between 5 and 6 and indicated that changes should occur briefly.

Conclusion

It was concluded that the most outstanding area in need of rapid changes was the surgical area, since it requires more effort on the part of these professionals. It is therefore proposed to implement new measures to improve health and well-being and avoid ergonomically incorrect postures.
Intraspecific variation in elemental accumulation and its association with salt tolerance inPaspalum vaginatum
Authors: Goad David M , Kellogg Elizabeth A , Baxter Ivan , Olsen Kenneth M
Published: August 2021

Most plant species, including most crops, perform poorly in salt-affected soils because high sodium levels are cytotoxic and can disrupt the uptake of water and important nutrients. Halophytes are species that have evolved adaptations to overcome these challenges and may be a useful source of knowledge for salt tolerance mechanisms and genes that may be transferable to crop species. The salt content of saline habitats can vary dramatically by location, providing ample opportunity for different populations of halophytic species to adapt to their local salt concentrations; however, the extent of this variation, and the physiology and polymorphisms that drive it, remain poorly understood. Differential accumulation of inorganic elements between genotypes or populations may play an important role in local salinity adaptation. To test this, we investigated the relationships between population structure, tissue ion concentrations, and salt tolerance in 17 “fine-textured” genotypes of the halophytic turfgrass seashore paspalum (Paspalum vaginatum Swartz). A high-throughput ionomics pipeline was used to quantify the shoot concentration of 18 inorganic elements across three salinity treatments. We found a significant relationship between population structure and ion accumulation, with strong correlations between principal components derived from genetic and ionomic data. Additionally, genotypes with higher salt tolerance accumulated more K and Fe and less Ca than less tolerant genotypes. Together these results indicate that differences in ion accumulation between P. vaginatum populations may reflect locally adapted salt stress responses.
Sweeps in time: leveraging the joint distribution of branch lengths
Authors: Bisschop Gertjan , Lohse Konrad , Setter Derek
Published: August 2021

Current methods of identifying positively selected regions in the genome are limited in two key ways: the underlying models cannot account for the timing of adaptive events and the comparison between models of selective sweeps and sequence data is generally made via simple summaries of genetic diversity. Here, we develop a tractable method of describing the effect of positive selection on the genealogical histories in the surrounding genome, explicitly modeling both the timing and context of an adaptive event. In addition, our framework allows us to go beyond analyzing polymorphism data via the site frequency spectrum or summaries thereof and instead leverage information contained in patterns of linked variants. Tests on both simulations and a human data example, as well as a comparison to SweepFinder2, show that even with very small sample sizes, our analytic framework has higher power to identify old selective sweeps and to correctly infer both the time and strength of selection. Finally, we derived the marginal distribution of genealogical branch lengths at a locus affected by selection acting at a linked site. This provides a much-needed link between our analytic understanding of the effects of sweeps on sequence variation and recent advances in simulation and heuristic inference procedures that allow researchers to examine the sequence of genealogical histories along the genome.