Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer patient stratification by next generation sequencing of circulating tumour DNA : taking the next steps towards implementation in the clinic

Recent advances in next generation sequencing (NGS) have allowed significant improvement in the sensitivity of detection of the tumour derived fraction of cell free DNA termed circulating tumour DNA (ctDNA). This thesis investigated the clinical application of ctDNA in serial plasma samples from breast cancer and gastroesophageal adenocarcinoma (GOA) patients undergoing palliative and curative treatment. Additionally, evaluation of tumour and ctDNA whole exome sequencing (WES) was completed on serial samples from one breast cancer patient. Targeted NGS was used to detect tumour specific mutations. The same technology and commercial/designed droplet digital assays were used to detect ctDNA. WES was undertaken in Spain and the resultant sequencing data analysed in-house. Ampliseq™ NGS detected ctDNA in 9 of 13 patients with metastatic breast cancer (69.2%). Detected mutations tracked disease progression and response. Oncomine™ NGS detected ctDNA in 5 out of 10 patients with pre and post neoadjuvant chemotherapy plasma samples. Two ctDNA positive patients relapsed, while none of the 5 ctDNA negative patients relapsed. WES of ctDNA was successfully undertaken. Mutations detected from ctDNA WES overlapped with WES of the primary and relapsed tumours. Key tumour mutations could be identified in ctDNA including ongoing mutational changes caused by tumour evolution. ctDNA was detected in a cohort of 44 patients with GOA. Nine of 13 (69.2%) metastatic patients with a detectable tumour mutation had detectable ctDNA. ctDNA levels tracked disease response and high levels of ctDNA at diagnosis of metastatic disease predicted short survival. Seven of 19 patients (36.8%) treated with curative intent that had a detectable tumour mutation had detectable ctDNA. Three patients had detectable ctDNA post surgery, two of whom relapsed during follow-up. Detection of ctDNA at any time prior to relapse predicted poor relapse free survival (HR 21.6, CI 2.5-185.5, p=0.005). This thesis demonstrates the potential clinical utility of ctDNA in both breast cancer and GOA and shows an emerging role for the use of ctDNA WES.
Impacto da aderência ao programa de controle de antimicrobianos na mortalidade de pacientes com neutropenia febril

Empirical therapy with broad-spectrum antimicrobial is part of the initial management of patients with febrile neutropenia (FN). Enough evidence on which antibiotics schemes should be initially prescribed already exists; however, no randomized study has evaluated whether adherence to antimicrobial stewardship programs (ASPs) results in lower rates of mortality from this syndrome. In the present prospective cohort study performed in a tertiary hospital, from October 2009 to August 2011, we evaluated the impact of adherence to ASP, measured by initial antimicrobial prescribing, in mortality of 295 episodes of FN (in 145 adults) that required intravenous inpatient treatment. After multivariate analysis through Cox regression, including other predictors of mortality, adherence to ASP proved to be an independent protective factor for death 28 days after the beginning of the episode of FN (adjusted hazard ratio [HR], 0.29; 95% confidence interval [95% CI], 0.11 to 0.72). The risk factors found to noncompliance to ASP were presence of hypotension (adjusted relative risk [RR], 1.90; 95% CI, 1.37 to 2.63), diarrhea (RR, 2.13; 95% CI, 1.66 to 2.73), perianal pain (RR, 2.08; 95% CI, 1.54 to 2.82), suspected source of infection in oral cavity (RR, 2.45; 95% CI 1.75 to 3.43) and cutaneous manifestations of infection (RR, 2.34; 95% CI, 1.81 to 3.04). The choice of antimicrobial is particularly important in the initial management of patients with fever in the presence of neutropenia; the adherence to ASP, which calls for rational use of antibiotics, was effective in reducing mortality during the course of the disease. The presence of signs or symptoms that demand changes in the initial therapy poses risks to nonadherence to the antimicrobial management program.
The Congenital Malformations in White Pregnant Mice Fetus Induced by Metformin Drug During 6-18 Days of Gestation

The metformin drug is anti-hyperglycemia and known to cross the placenta which leads to the fetus during pregnancy . The aim of this study is to define the drug effects in the fetus growth . The doses used , therapeutic dose ( 0.18 & 0.53 ) mg\25g body weight and over dose ( 1.8 & 2.85) mg\ 25g body weight , administrated orally at the beginning organogenesis stage at ( 6 -18 ) day of pregnancy in the morning . A total ( 50 ) animal were divided into five groups . The first group control not treated , 2nd group treated with (0.18) mg , 3rd group with ( 0.53 ) mg , 4th group with ( 1.8 ) mg and 5th group with ( 2.85 ) mg . In this study noted some congenital malformations in the fetus compared with normal control group , which included in the 2nd and 3rd group ( irregular body level , exophthalmia , micromelia , elevated some hand fingers , simple club foot , torsion tail and wrinkle skin ) while the defects was larger in the 4th and 5th group ( trunk abnormalities like C Shape , big head ( scaphocethaly) , cranial flexure , prosencephaly, short neck , micromelia , syndactyly some of hand fingers and others hemimelia , torsion tail and some aquiline , sharply club foot and spina bifida ) . It is mentioning that the malformations was less in the 2nd group treated with (0.18) mg of the drug . The treatment with metformin drug during pregnancy induced the congenital malformations .
Real-world clinical outcomes of anticancer treatments in patients with advanced melanoma in China: retrospective, observational study

Introduction: Treatment options for advanced melanoma in China are lacking, particularly second-line therapies. The aim of this retrospective observational study was to describe the real-world effectiveness of available anticancer therapies in patients with locally advanced/metastatic melanoma in China. Methods: Adult patients with unresectable stage III or IV melanoma treated between January 1, 2014, and December 31, 2015, at the Beijing Cancer Hospital (BCH) were eligible (data cutoff: December 31, 2017). Data were obtained from patient electronic medical records. Responders were adjudicated per Response Evaluation Criteria in Solid Tumors, version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Of 248 eligible patients, 221 and 116 were treated with anticancer therapies in first-line and second-line settings, respectively (89 received both at BCH). Approximately 95% of patients had stage IV melanoma; 40.7% had acral melanoma, and 30.6% had mucosal histology. By data cutoff, 195 of 248 (78.6%) patients had died. Median OS for all patients was 10.5 months; 12-month OS rate was 43.9%. In the first-line setting, the objective response rate was 6.3% (95% confidence interval, 3.5%–10.4%) and the median duration of response was 9.1 months. Median PFS was 3.5 months and 12-month PFS rate was 10.6%; median OS was 10.5 months and 12-month OS rate was 43.5%. In the second-line setting, objective response rate was 3.4% (95% confidence interval, 0.9%–8.6%) and median duration of response was 7.5 months. Median PFS was 2.3 months and 12-month PFS rate was 5.2%; median OS was 7.5 months and 12-month OS rate was 30.5%. Conclusion: In China, first-line and second-line anticancer therapy seems to be associated with suboptimal clinical outcomes in advanced melanoma, indicating a need for effective therapies.
The Pre-Exposure Prophylaxis (PrEP) Stigma Scale: Preliminary findings from a pilot study.

Despite being at the cornerstone of current initiatives to curtail the spread of HIV, Pre-Exposure Prophylaxis (PrEP) medication has been slow to proliferate among many "at risk" populations. This is true for men who have sex with other men (MSM), who account for the largest number of new HIV diagnoses in the United States. To try to understand why MSM are not adopting PrEP in greater numbers, the present authors have created a 22-item PrEP Stigma Scale. This paper reports findings for that scale. METHODS Purposive sampling was used to derive a sample of 273 diverse MSM. Men completed a brief questionnaire inquiring about their awareness of PrEP, willingness to avail themselves of various sources of information about PrEP, perceptions about PrEP-related stigma, and perceptions about obstacles to PrEP use. Cronbach's alpha reliability coefficients were computed for the PrEP Stigma Scale, for the full sample and for key subgroups. Factor analysis was performed to determine whether or not subscales exist. RESULTS The PrEP Stigma Scale was found to be highly reliable, both in its full version (alpha=0.96) and in its shortened version (alpha=0.95). Reliability estimates were strong for all subgroups based on age, race, sexual orientation, educational attainment, relationship status, and HIV serostatus. Two subscales were identified, each with excellent reliability (alpha=0.95 and 0.94), again for the sample as a whole and for all key subgroups. CONCLUSIONS The PrEP Stigma Scale shows great promise for aiding our understanding of why more MSM are not adopting PrEP. It was found to be reliable for all key subgroups under examination, and that is true both for the 22-item and the 11-item version of the scale.
Prevalência de Oclusão Normal e Má Oclusão em Brasileiros, Adultos, Leucodermas, Caracterizados pela Normalidade do Perfil Facial Prevalence of Normal Occlusion and Malocclusion among Adult, Caucasian Brazilians, with Normal Facial Profile

O objetivo do presente estudo foi determinar a prevalencia de oclusao normal e das mas oclusoes de Classe I, Classe II (divisoes 1 e 2) e Classe III em uma amostra constituida com o objetivo de representar a populacao de brasileiros, adultos, leucodermas, nao tratados ortodonticamente e caracterizados pela normalidade do perfil facial. O criterio de selecao inicialmente utilizado foi o selamento labial passivo, considerado como a condicao minima para a normalidade funcional do perfil. Cem individuos (50 de cada genero) foram moldados e fotografados de perfil e a classificacao da relacao oclusal sagital revelou que 7 por cento da amostra apresentou oclusao normal e 93 por cento mas oclusoes, sendo 48 por cento Classe I, 36 por cento Classe II, divisao 1, 6 por cento Classe II, divisao 2 e 3 por cento Classe III. O carater de normalidade da amostra foi acentuado com a exclusao de 8 individuos considerados esteticamente desagradaveis por uma banca heterogenea de examinadores. A amostra resultante era entao caracterizada pela normalidade funcional e estetica do perfil facial. Esse grupo apresentou 7,6 por cento de oclusao normal, 48,91 por cento ma oclusao Classe I, 34,78 por cento Classe II, divisao 1, 5,44 por cento Classe II, divisao 2 e 3 por cento Classe III. Finalmente, foram excluidos os 7 individuos portadores de oclusao normal, que nao teriam indicacao de tratamento ortodontico. A prevalencia dde mas oclusoes foi entao determinada para os adultos com indicacao de tratamento ortodontico, portadores de normalidade funcional e estatica do perfil, representada pelo selamento labial passivo e pela aparencia estetica aceitavel ou agradavel, que, portanto, teriam bom prognostico para a correcao ortodontica. O resultado obtido foi 52,94 por cento Classe I, 37,64 por cento Classe II, divisao 1, 5,9 por cento Classe II, divisao 2 e 3,52 por cento Classe III (AU)
Segmentation of Kidney and Tumor using Auxiliary Information

Automatic segmentation of organs and tumors is a prerequisite of many clinical application in radiology. The anatomical variability of organs in the abdomen and especially of tumors makes it diﬃcult for many methods to obtain good segmentations. in this report we present a cascade of two convolutional neural networks allowing to segment an organ followed by the segmentation of a tumor. The advantage of the proposed pipeline is that the preliminary organ segmentation, which is a simpler task, helps the further segmentation of the tumor. The proposed system was evaluated using the KiTS19 challange dataset.
Overview of Meta-Analyses: The Impact of Lifestyle on Stroke Risk

Stroke is one of the most prevalent cardiovascular diseases worldwide, both in high-income countries and in medium and low-medium income countries. The WHO report on non-communicable diseases (NCDs) indicates that the highest behavioral risk in NCDs is attributable to incorrect nutrition. The objective of our work is to present an overview of meta-analyses that have investigated the impact of different foods and / or drinks in relationship with the risk of stroke events (ischemic/ hemorrhagic). The papers to be included in the overview were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library and were selected according to PRIMA flow chart. Quality assessment were made according to AMSTAR scale. This overview shows that all primary studies came from countries with high income level. This evidence shows that many countries are not represented. Therefore, different lifestyles, ethnic groups, potentially harmful or virtuous eating habits are not reported. It is important to underline how the choose of foods may help reduce the risk of cardiovascular diseases and stroke in particular.
Sexual Dimorphism in Aortic Function of UC Davis Type 2 Diabetes Mellitus Rat Model: Estrogen Specific Responses

By Farjana Akther University of the Pacific 2019 Little is known about the interaction between diabetes and sex in vasculature. This study was designed to investigate the effects of estrogen as well as type 2 diabetes (T2D) on aortic function in rats with respect to sex. To test the effects of T2D and sex, UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model was used. To study the effects of estrogen, ovariectomized SpragueDawley female rats and UCD-T2DM rats at pre-diabetic stage were used and the rats were implanted subcutaneously either with placebo or 17 β-estradiol pellets (60 days release, 1.5mg/pellets). The plasma analytes for metabolic parameters and aortic responses to vasodilator and vasoconstrictor agents were determined. The expression of molecules associated with vascular response (e.g. endothelial nitric oxide (NO) synthase (eNOS), Nox1, Nox4, intermediate conductance calcium-dependent potassium channels (IKCa) and small conductance calcium-dependent potassium channels (SKCa)) were also evaluated in aortic tissue. The main objectives of the study were whether 1) sex differences exist in the development of abnormal vascular responses of UCD-T2DM rats, 2) there were changes in the relative contributions of endothelium-derived relaxing factors (EDRFs) in modulating vascular reactivity of aorta, and 3) estrogen replacement improves the aortic function of ovariectomized UCD-T2DM rats at pre-diabetic stage.
EFEMP2 Inhibits Breast Cancer Invasion And Metastasis In Vitro And In Vivo

Background EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) is an extracellular matrix (ECM) glycoprotein, which is regarded as potential prognostic biomarkers in some carcinoma. Little is known about the association of EFEMP2 and breast cancer. Methods EFEMP2 expressions in normal breast tissue, benign fibroadenoma, breast cancer, the normal mammary epithelial cell line, and 4 different invasive breast cancer cell lines were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Expression and prognostic value of EFEMP2 in breast cancer were verified by the Public databases (Oncomine and Kaplan-Meier plotter database). Lentiviral vector with EFEMP2 cDNA was constructed and used to infect breast cancer cell lines to investigate the effects of EFEMP2 on the biological behavior of breast cancer cells by functional in vitro and in vivo assays. Results Down-regulated EFEMP2 expression was found in breast cancer tissues and cells, and low expression of EFEMP2 was associated with poor prognosis in patients with breast cancer. Analysis by the Public database leaded to the same conclusion. Up-regulated EFEMP2 expression significantly hampered the invasion and metastasis abilities of breast cancer cells and the process of epithelial interstitial transformation (EMT) via the Wnt/β-catenin pathway. Conclusion EFEMP2 expression was lower in breast cancer and closely related to the prognosis of patients, its anti-oncogenic roles indicated the underlying therapeutic target for the future treatment of breast cancer.
TNF-α accelerates the calcification of human aortic valve interstitial cells obtained from patients with calcific aortic valve stenosis via the BMP2-Dlx5 pathway

Calcific aortic valve stenosis (CAS) is the most frequent heart valve disease in the elderly, accompanied by valve calcification. Tumor necrosis factor-α (TNF-α a pleiotropic cytokine secreted from macrophages, has been detected in human calcified valves. However, the role of TNF-α in valve calcification remains unclear. To clarify whether TNF-α of aortic valves, we investigated the effect of TNF-α on human aortic valve interstitial cells (HAVICs) obtained from patients with CAS (CAS group) and with aortic regurgitation or aortic dissection having a noncalcified aortic valve (control group). HAVICs (2 × 10 4 ) were cultured in a 12-well dish in DMEM with 10% fetal bovine serum. The medium containing TNF-α (30 ng/ml) was replenished every 3 days after the cells reached confluency. TNF-α significantly accelerated the calcification and alkaline phosphatase (ALP) activity of HAVICs from CAS but not the control group after 12 days of culture. Furthermore, gene expression of calcigenic markers, ALP, bone morphogenetic protein 2 (BMP2), and distal-less homeobox 5 (Dlx5) were significantly increased after 6 days of TNF-α treatment in CAS but not control group. Dorsomorphin, an inhibitor of mothers against decapentaplegic homologs (Smads) 1/5/8 phosphorylation, significantly inhibited the enhancement of TNF-α -induced calcification, ALP activity, Smad phosphorylation, and Dlx5 gene expression of HAVICs from the CAS group. These results suggest that HAVICs from the CAS group have greater sensitivity to TNF-α which accelerates the calcification of aortic valves via the BMP2-Dlx5 pathway. aortic valve interstitial cells (HAVICs) from CAS compared with a control group. Results indicated that TNF-α accelerated calcification of HAVICs by elevating alkaline phosphatase (ALP) activity and ALP gene expression in the CAS group. We further investigated the molecular mechanism of TNF-α induced calcification of HAVICs in the CAS group and found critical roles for BMP2 and Dlx5 in aortic valve calcification. accelerate BMP2 gene expression mainly via NF- κ B signaling, translocation of NF- κ B p65 subunit into the nucleus. BMP2 stimulates the Dlx5 gene expression resulting in ALP activation followed by ectopic calcification, via Runx2 activation. It is hoped that these results will help to further clarify the mechanism of aortic valve calcification and develop new therapies for aortic valve stenosis.
Effects of perinatal distress, satisfaction in partner relationship and social support on pregnancy and outcome of childbirth

Jonsdottir, Sigridur Sia (2019). Effects of perinatal distress, satisfaction in partner relationship and social support on pregnancy and outcome of childbirth, Linnaeus University Dissertations No 352/2019, ISBN: 978-91-88898-60-9 (print), 97891-88898-61-6 (pdf). Aim: The aim of this thesis was to achieve a deeper understanding of the situation among women experiencing perinatal distress during pregnancy and childbirth and the effects that dissatisfaction in partner relationship and weak social support from family and friends could have on pregnancy and childbirth. Methods: Following screening for perinatal distress, 562 expecting mothers came for a semi-structured interview. This screening, done with the Depression Anxiety Stress Scales and the Edinburgh Postpartum Depression Scale, categorized 360 (64.1%) women into the perinatal distressed group (PDG) and 202 (35.9%) into the non-distressed group (NDG). During the interview women answered the Dyadic Adjustment Scale and the Multidimensional Scale of Perceived Social Support. Data were collected with these instruments for study I. Additional data for the three other studies were gathered from the women ́s pregnancy records (II), electronic medical records (II, III), and childbirth records (IV). Results of the four studies were obtained by using descriptive statistics; parametric and nonparametric statistics and regression modeling. Results: Women in the PDG were significantly more likely than the NDG to be dissatisfied in their partner relationship, continue smoking during pregnancy, be dissatisfied with division of household tasks and child-rearing, have elementary or lower education, and to be students or unemployed. They were also significantly more likely to experience fatigue, vomiting and pelvic girdle pain during pregnancy. Women in the PDG who received weak family support reported nausea and heartburn more frequently than those with strong family support. Women in the PDG utilized more antenatal care service and were allocated more part time as well as earlier sick leaves during pregnancy, than those in the NDG. Women in the PDG were significantly more likely to use epidural anesthesia as a single pain management during labor. Conclusion: Perinatal distress affects pregnancy and childbirth. It is more common among women who are dissatisfied in their partner relationship and with the division of household tasks and child-rearing. Perception of weak social support also affects pregnancy among distressed women. Distressed women along with their partners and families should be offered support and consultation to relieve distress and strengthen their bonds during pregnancy and childbirth.
Meaningful work for a meaningful life? Work alienation and its effects in the work and the family context

textabstractAbstract. The notion of work alienation and its consequences has fascinated scholars and practitioners for a long time. But most research focused on passive performance indicators (such as job satisfaction), while the effects on work alienation on active performance (work effort) and outside work are understudied. This paper therefore examines the impact of work alienation on passive performance (organizational commitment), active performance (work effort), and its impact outside work (workfamily enrichment). Hypotheses are formulated based on two research streams: sociology of work and organization in relation to work alienation and work-family literature in relation to enrichment. Two dimensions of work alienation are considered: powerlessness and meaninglessness. Both literature streams expect a negative impact of work alienation on employee outcomes. Hypotheses are tested on survey data collected among a national sample of midwives in the Netherlands (respondents: 790, response rate 61%). Findings indicate that work alienation does not only have an impact on passive performance, but also on active performance and outside work. In particular work meaninglessness is relevant for outcomes. This underscores the importance of lowering the degree of work alienation, which has effects inside and outside the work context.
Sleep · 9: An approach to treatment of obstructive sleep apnoea/hypopnoea syndrome including upper airway surgery

This article provides an overview of the management of the obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Where possible, recommendations are based on a review of the relevant literature. With the exception of nasal continuous positive airway pressure, which is considered in greater detail elsewhere in the series, and certain oral appliances, the efficacy of many proposed treatments for OSAHS is not supported by data from randomised controlled clinical trials. To a considerable extent, treatment recommendations are based on data from uncontrolled studies, case series, consensus guidelines, practice parameters, and other less rigorous forms of evidence.