Miracle-dz/UniFAR-FTUs huggingface dataset:
IBSP, a potential recurrence biomarker, promotes the progression of colorectal cancer via Fyn/β‐catenin signaling pathway

Colorectal cancer (CRC) is a frequently occurring digestive system cancer and postoperative tumor metastasis and recurrence are the main reasons for the failure of CRC treatment. The aim of this study was to identifying and validating key genes associated with metastatic recurrence of CRC. RNA expression of three datasets (GSE17538, GSE32323, and GSE29623) was used for biomarker discovery. We identified integrin‐binding sialoprotein (IBSP) as a candidate biomarker which was validated in three clinical cohorts (GSE41258, GSE21510, and GSE39582) and our clinical specimens. The results suggested that IBSP expression significantly increased at mRNA and protein levels among CRC cases, which was associated with metastatic recurrence, metastasis, high risk of recurrence, and poor survival in CRC. Consistent results were obtained in CRC cells. The relative level of serum IBSP evidently increased among CRC patients relative to normal controls, and downregulated after operation. As suggested by gene set enrichment analysis (GSEA), the IBSP level was associated with cell‐matrix adhesion in CRC. Functional experiments in vitro showed that IBSP promoted the growth and aggressiveness of CRC, and the potential mechanism by which IBSP promoted carcinogenesis of CRC was the abnormal activation of Fyn/β‐catenin signaling pathway. To sum up, findings in the present work indicate that IBSP can serve as the candidate biomarker for the diagnosis, treatment, and prognosis of CRC.
Vibrational Spectroscopy for Detection of Diabetes: A Review

Type II diabetes mellitus (T2DM) is a metabolic disorder that is characterized by chronically elevated glucose caused by insulin resistance. Although T2DM is manageable through insulin therapy, the disorder itself is a risk factor for much more dangerous diseases including cardiovascular disease, kidney disease, retinopathy, Alzheimer’s disease, and more. T2DM affects 450 million people worldwide and is attributed to causing over four million deaths each year. Current methods for detecting diabetes typically involve testing a person’s glycated hemoglobin levels as well as blood sugar levels randomly or after fasting. However, these methods can be problematic due to an individual’s levels differing on a day-to-day basis or being affected by diet or environment, and due to the lack of sensitivity and reliability within the tests themselves. Vibrational spectroscopic methods have been pursued as a novel method for detecting diabetes accurately and early in a minimally invasive manner. This review summarizes recent research, since 2015, which has used infrared or Raman spectroscopy for the purpose of developing a fast and accurate method for diagnosing diabetes. Based on critical evaluation of the reviewed work, vibrational spectroscopy has the potential to improve and revolutionize the way diabetes is diagnosed, thereby allowing for faster and more effective treatment of the disorder. Graphical Abstract
Spectroscopy of low and intermediate Z elements at extreme conditions: in situ studies of Earth materials at pressure and temperature via X-ray Raman scattering

ABSTRACT X-ray Raman scattering spectroscopy is an emerging method in the study of low and intermediate Z elements' core-electron excitations at extreme conditions in order to reveal information on local structure and electronic state of matter in situ. We discuss the capabilities of this method to address questions in Earth materials' science and demonstrate its sensitivity to detect changes in the oxidation state, electronic structure, coordination, and spin state. Examples are presented for the study of the oxygen K-, silicon L- and iron M-edges. We assess the application of both temperature and pressure in such investigations exploiting diamond anvil cells in combination with resistive or laser heating which is required to achieve realistic conditions of the Earth's crust, mantle, and core.
Strawberry fruit skins are far more permeable to osmotic water uptake than to transpirational water loss

Water movements through the fruit skin play critical roles in many disorders of strawberry (Fragaria × ananassa Duch.) such as water soaking, cracking and shriveling. The objective was to identify the mechanisms of fruit water loss (dry skin, transpiration) and water uptake (wet skin, osmosis). Fruits were held above dried silica gel or incubated in deionized water. Water movements were quantified gravimetrically. Transpiration and osmotic uptake increased linearly with time. Abrading the thin cuticle (0.62 g m-2) increased rates of transpiration 2.6–fold, the rates of osmotic uptake 7.9-fold. The osmotic potential of the expressed juice was nearly the same for green and for white fruit but decreased in red fruit stages. Fruit turgor was low throughout development, except for green fruit. There was no relationship between the rates of water movement and fruit osmotic potential. The skin permeance for transpiration and for osmotic uptake were both high (relative to other fruit species) but were two orders of magnitude greater for osmotic uptake than for transpiration. Incubating fruit in isotonic solutions of osmolytes of different sizes resulted in increases in fruit mass that depended on the osmolyte. The rate of osmotic uptake decreased asymptotically as molecular size of the osmolyte increased. When transpiration and osmotic uptake experiments were conducted sequentially on the same fruit, the rates of transpiration were higher for fruit previously incubated in water. Fluorescence microscopy revealed considerable microcracking in a fruit previously incubated in water. Our findings indicate that the high permeance for osmotic uptake is accounted for by an extremely thin cuticle and by viscous water flow through microcracks and along polar pathways.
Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature

Abstract Background Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. Methods Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English. Results Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death. Conclusions Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
Right ventricular systolic function is associated with health-related quality of life: a cross-sectional study in community-dwelling populations

Background Considerable evidence has been presented that heart and health-related quality of life are directly linked in patients with various diseases. This exploratory study investigated whether cardiac structure and function were associated with health-related quality of life in the general population. Methods This cross-sectional study was performed in five villages of Shunyi, a suburban district of Beijing, from June 2013 to April 2016. All inhabitants aged 35 years or older living in five villages of Shunyi were invited to participate. Exclusion criteria were individuals who declined participation, who had incomplete Health-related quality of life (HRQoL) data, and who had suboptimal echocardiograms. HRQoL was evaluated by the Mandarin version of SF-36. The association between the echocardiography-derived cardiac structure and function and each domain of SF-36 was analyzed by the multivariate linear regression analysis after adjusted for conventional risk factors affecting HRQoL. Results The baseline data of 990 individuals were analyzed. The median age of the participants was 57 (50–63) years, and 367 (37.1%) were male, the average physical and mental component summary scores were 89.3 (79.8–94.3) and 90 (83.5–95) respectively. Tricuspid annular plane systolic excursion, an echocardiography-derived right ventricular parameter, was associated with all the subscales and summarized scores of SF-36 (all P<0.05). The independent association between tricuspid annular plane systolic excursion and physical/mental component summary scores remained after adjusting for age, gender, body mass index, education level, annual personal income, smoking and drinking status, and comorbidities (β=0.65, 95% confidence interval 0.30–1.01, P<0.01 and β=0.49, 95% confidence interval 0.23–0.76, P<0.01 for physical and mental component summary scores respectively). Compared with the participants with tricuspid annular plane systolic excursion ≥21 mm, the participants with tricuspid annular plane systolic excursion <21 mm had lower adjusted scores of physical and mental component summary scores (81.8 vs. 84.5, P=0.015, and 85.5 vs. 88.1, P<0.01 for physical and mental component summary scores respectively). Conclusions In this population-based study, right ventricular systolic function assessed by tricuspid annular plane systolic excursion was independently associated with health-related quality of life assessed by SF-36.
Histopathological Features in Colonic Biopsies at Diagnosis Predict Long-term Disease Course in Patients with Crohn’s Disease

Abstract Background and Aims Crohn’s disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course. Methods Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. Results In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%). Conclusions In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.
Stress perceived by students of the medical sciences in Cuba toward the COVID-19 pandemic: results of an online survey

Introduction: The aims of this study were to determine the usefulness of the Modified (10-items) Scale of Stress perceived related to COVID-19 (EEP-10-C by its acronym in Spanish) and to identify the levels of stress perceived by students of the medical sciences in Cuba toward the COVID-19 pandemic. Methods: A cross-sectional study was conducted, with self-reported data of students from fourteen Cuban Universities of Medical Sciences ( 200), through an online survey. The EEP-10-C was used as an instrument to identify stress. Its validity was determined through a confirmatory factor analysis and its internal consistency and reliability was measured by the Cronbach alph. A cluster analysis was performed to establish as cut-off point the center of the cluster with the highest values of stress perceived by the scale. Results: The average age of the sample was 23.30 +- 1.91 years, with observed scores of the EEP-10-C between 0 and 29 points (13.25 +- 5,404). When applying the cut-off point 25, only two students had high rates of stress perceived. The confirmatory factor analysis supported the validity of the instrument; with a Cronbach's alpha of 0.755. The cutoff point 20 was proposed as a reference of high stress perceived for the study population, when applying this one, 14% of students presented high rates of stress. Discussion: In Cuba, students of the medical sciences have participated in research and supporting health care, despite which they have presented low levels of stress. The main contribution of the research was the validation of the EEP-10-C for its use in assessing levels of stress in Cuban medical students, proposing the cut-off point 20 as a reference of high stress perceived. Keywords: coronavirus disease, COVID-19, stress perceived, stress perceived scale, medicine students.
Advanced Paternal Age and Sperm DNA Fragmentation: A Systematic Review

Purpose Male ageing is often associated with defective sperm DNA remodeling mechanisms that result in poorly packaged chromatin and a decreased ability to repair DNA strand breaks. However, the impact of advanced paternal age on DNA fragmentation remains inconclusive. The aim of the present systematic review was to investigate the impact of advancing paternal age (APA) on DNA fragmentation. Materials and Methods We conducted a thorough search of listed publications in Scopus, PubMed, and EMBASE, in accordance with the PRISMA guidelines. Results We identified 3,120 articles, of which nineteen were selected for qualitative analysis, resulting in a sample of 40,668 men. Of the 19 articles evaluating the impact of APA on DFI% (DNA fragmentation Index) included, 4 were on Normozoospermic and subfertile men, 3 on normozoospermic, Oligoasthenoteratozoospermic and Teratozoospermic, 6 on fertile and infertile men, 4 on just infertile men, and 2 evaluated a general population. Seventeen of the ninrnteen studies demonstrated APA's effect and impact on DFI%. Conclusions Although there was no universal definition for APA, the present review suggests that older age is associated with increased DFI. In elderly men with normal semen parameters, further studies should be performed to assess the clinical implications of DFI, as a conventional semen analysis can often fail to detect an etiology for infertility.
An improvised controlled release tablet of salbutamol sulphate

Two formulations of controlled release hydrophillic matrix tablets of salbutamol sulphate based on Hydroxypropylmethylcellulose and its combination with guar gum have been reported. Formulations showing an appropriate in vitro release pattern were evaluated for in vitro activity and have exhibited a sustained bronchodilatory effect. Accelerated stability studies indicate that storage of these formulations at high temprature and humidity should be avoided.
Evaluation of a high forage total mixed ration on the lactational performance of late lactation dairy cows

Abstract Dairy producers continuously ask questions challenging the paradigm of how much forage can be included in the ration to meet the nutrient requirements of lactating dairy cows to support milk production. The production and feeding of forages having both high dry matter digestibility (DMD) and neutral detergent fiber digestibility (NDFd) are needed to increase nutrient supply. Mid- to late-lactation lactating Holstein dairy cows were blocked by parity (10 primiparous and 10 multiparous), milk production (range 33.9 to 56.6; μ = 41.5 kg/d), and days in milk (DIM) (range 140 to 287; μ = 225 d) and randomly assigned within blocks to 1 of 2 rations based on medium forage (MF) or high forage (HF) inclusion rates. A forage blend consisting of 60% second cutting (2012) alfalfa haylage and 40% (2012) corn silage blended on a DM basis and then fed at either 60% (MF) or 80% (HF) of the ration DM. The alfalfa haylage DM (DMD = 75.7%) and NDF (NDFd = 55.7%) digestibility was above average, but corn silage (DMD = 72.9, NDFd = 52.3%, and starch = 32.1%) was average. The experimental design was a randomized completed block design with 4 continuous weeks for data collection preceded by a 1 wk covariate data collection period in which all cows were fed the MF ration. Cows were milked 3 times/d and milk weights recorded at each milking and milk samples were collected at each milking once weekly for analysis of milk composition. Rations were similar in crude protein (CP; 16.4%), starch (20.1%), acid detergent fiber (ADF; 21.8%), and NDF (34.1%) concentrations. Covariately adjusted milk production (28.1 and 24.1 kg/d for MF and HF, respectively) and 4% fat-corrected milk (FCM; 27.6 and 24.1 kg/d) were significantly reduced by feeding the HF ration compared with cows fed the MF ration, while milk fat (3.98 and 4.0%), milk protein (3.11 and 3.17%), milk lactose (4.81 and 4.77%), and milk solids-not-fat (8.87 and 8.77%) percentages were similar for cows fed both rations. Cows on the HF ration demonstrated a significant reduction in DMI and a trend for decreased body weight (BW) when compared with cows fed the MF ration. The forage nutrient digestibility was not adequate to support the milk production of mid- to late-lactation dairy cows when fed at 80% of the DM. The forage nutrient digestibility when fed at very high inclusion rate (80%) could not meet the nutrient requirements of mid- to late-lactation dairy cows.
Methylated biomarkers for breast cancer identified through public database analysis and plasma target capture sequencing

Background Aberrant methylation is common during the early stage of cancer development. This study was designed to investigate DNA methylation as biomarker for breast cancer. Methods Public database analysis and methylation-specific whole-gene sequencing were conducted to identify methylated biomarkers that would enable early non-invasive diagnosis of breast cancer. Firstly, the data was obtained from the TCGA Database and the Blueprint Epigenome Database. Secondly, methylation-specific whole-gene sequencing was conducted in 10 female patients with early-stage breast cancer and 10 healthy female volunteers from Nanfang Hospital of Southern Medical University between March 2018 and July 2018. Thirdly, the R language was used for data analysis, and KEGG and DAVID online tool was used for annotations. Results We found that methylation levels at 13 cytosine-phosphate-guanine (CpG) sites (cg04066177, cg04281344, cg05995576, cg06221609, cg08642731, cg11388802, cg12665414, cg14557216, cg19404723, cg19457909, cg24570211, cg25818763, and cg26215982) in the malignant tissue DNA were highly comparable to those of circulating cell-free DNA (cfDNA) of breast cancer patients, but were significantly different from those of normal tissue DNA, cfDNA of healthy women, and leukocyte DNA. In addition, three CpG sites (cg04281344, cg24570211, and cg26215982) were confirmed in clinical research, which showed that the sensitivity and specificity of these CpGs as biomarkers for breast cancer were 69.4–83.7% and 85.7–88.6%, respectively. Conclusions New biomarkers were identified and confirmed for breast cancer by comparing the methylation of tumour tissues, leukocytes, and non-plasma DNA.
An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients

Cannabis‐based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high‐quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health‐related quality of life and clinical safety.
A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing

Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organisation, induces intestinal autophagy through transcriptional regulation, and prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting that the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.