Miracle-dz/UniFAR-FTUs huggingface dataset:
Mass spectrometry analysis of glycoprotein biomarkers in human blood of hepatocellular carcinoma

ABSTRACT Introduction: Diagnosis of hepatocellular carcinoma (HCC) is important for improving the survival rate and selecting the optimum therapeutic option. However, some patients with HCC are not diagnosed until after symptoms appear, when the tumor is already advanced. Thus, biomarkers associated with HCC and novel diagnostic methods are required to improve the diagnosis of HCC. Mass spectrometry (MS) is one of the most widely used analytical tools in proteomic research. Furthermore, tandem MS (MS/MS) has been applied for the discovery and verification of protein biomarkers for clinical use. Areas covered: We review candidate glycoprotein biomarkers, including their aberrant glycosylation discovered by MS-based proteomics techniques and their diagnostic strategies using human blood samples. Finally, we discuss the limitations and prospects of MS-based approaches for clinical applications. Expert commentary: The development of biomarkers with high sensitivity and specificity is essential for optimizing the management of HCC. Various glycoprotein biomarkers of HCC have been identified using MS-based techniques. MS-based assays will continue to play an important role in clinical applications for discovery and verification of biomarkers. Furthermore, combination of multibiomarker, improvements in sample enrichment and the development of highly sensitive MS methods will facilitate more rapid adoption of MS for the diagnosis of HCC.
Time-Efficient Allocation Mechanisms for Crowdsensing Tasks with Precedence Constraints †

Crowdsensing has emerged as an efficient and inexpensive way to perform specialized tasks by leveraging external crowds. In some crowdsensing systems, different tasks may have different requirements, and there may be precedence constraints among them, such as the Unmanned Aerial Vehicle (UAV) crowdsensing systems. Moreover, minimizing the total execution time is a regular target for finishing the crowdsensing tasks with precedence constraints. As far as we know, only a few existing studies consider the precedence constraints among crowdsensing tasks, and none of them can minimize the total execution time simultaneously. To tackle this challenge, an efficient allocation mechanism for tasks with precedence constraints is first proposed, which can minimize the total execution time. Then, a case study is given to show how to fit our mechanism in the UAV crowdsensing system. Finally, the simulation results show that the proposed mechanisms have good approximate optimal ratios under different parameter settings and are efficient for the UAV crowdsensing system as well.
Chronic Pain, Physical Activity, and All-Cause Mortality in the US Adults: The NHANES 1999-2004 Follow-Up Study

Purpose: The purposes of this study were (1) to examine the relationship between chronic pain and the risk of all-cause mortality and (2) to explore the role of physical activity (PA) in this relationship. Design: Prospective cohort study. Setting: The National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Participants: A total of 7384 adults aged ≥40 years old. Measures: Chronic pain and PA were assessed based on the responses to miscellaneous pain and leisure-time PA questionnaires collected during the household interview. The 2011 mortality data from the National Center for Health Statistics were linked to the NHANES participants. Analysis: Cox proportional hazard analyses after accounting for the complex sampling design of the NHANES. Results: After adjusting for several key covariates including sociodemographic variables, chronic health conditions, and unhealthy lifestyle behaviors, individuals with localized or widespread chronic pains showed greater risk of all-cause mortality when compared to individuals with no chronic pain (hazard ratios [HRs] = 1.26 and 1.41, respectively). However, the association was attenuated by further adjustment of PA levels, where engagement of PA ≥150 min/wk was associated with reduced risk of mortality regardless of chronic pain conditions (P for trends between <.001 and .028). The joint analysis further demonstrated that individuals with localized or widespread chronic pains who had PA ≥150 min/wk had lower risk of mortality (HRs = 0.53 and 0.58, respectively) when compared to those without chronic pain who reported no leisure time PA. Conclusion: This study highlighted the important role of PA in reducing the risk of mortality for individuals with chronic pain. Further public health efforts to promote PA in this vulnerable population group are required.
Radical prostatectomy for high-risk prostate cancer | Opinion: NO

Prostate cancer (PC) is the most common solid malignancy in men. In 2019, there are expected to be 174,000 new diagnoses in the United States with 31,000 patients ultimately succumbing to their disease (1). Those with more aggressive disease are at a greater risk of local treatment failure and death (2), thus emphasis on the appropriate management for the subset of patients with high risk PC (HRPC) is paramount. Current guideline recommendations for patients with HRPC include radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) or EBRT plus brachytherapy (BT) and ADT (3-6). Each guideline panel separately defines the criteria that place patients at higher risk of adverse outcomes. These criteria include a combination of preoperative prostate specific antigen (PSA), biopsy Gleason score and clinical stage (Table-1). Herein, it is our goal to highlight the differences in outcomes amongst these treatment options, the heterogeneity that exists within the HRPC category and to show where the evidence for treatment of HRPC with surgery is lacking.
Monitoring the dynamics of social stratification: Statural variation among polish conscripts in 1976 and 1986

The effects of three factors in the social environment on variation in stature were evaluated in two large samples of 19‐year‐old Polish conscripts, one examined in 1976 (birth cohort 1957) another in 1986 (birth cohort 1967). The factors were: A) population size of the locality of the conscript's habitation, B) occupational‐educational status (OES) of the father, and C) size of the conscript's sibship. In each cohort, stature decreased monotonically with decreasing population size, decreasing paternal OES and increasing sibship size, each factor exerting a significant influence on stature even after the influences of the other two were partialled‐out by analysis of variance (ANOVA) procedures. However, the order of the strenght of the influences has changed from B > C > A in 1976 to C > B = A in 1986. The most notable change was the decline in the importance of factor B. The condition of being a peasant's son depressed stature less in 1986 than in 1976, but the stature‐depressing effect of the condition of being a rural dweller, as well as that of coming from a large family, has not diminished. Overall, secular gains in stature among groups lowest on the statural and social scale in 1976 have been more intense than among those highest on these scales, which resulted in an attenuation of some social contrasts in stature from 1976 to 1986. © 1992 Wiley‐Liss, Inc.
The role of viral infections in the development of autoimmune diseases

Abstract The exact aetiology of most autoimmune diseases remains unknown, nonetheless, several factors contributing to the induction or exacerbation of autoimmune reactions have been suggested. These include the genetic profile and lifestyle of the affected individual in addition to environmental triggers such as bacterial, parasitic, fungal and viral infections. Infections caused by viruses usually trigger a potent immune response that is necessary for the containment of the infection; however, in some cases, a failure in the regulation of this immune response may lead to harmful immune reactions directed against the host’s antigens. The autoimmune attack can be carried out by different arms and components of the immune system and through different possible mechanisms including molecular mimicry, bystander activation, and epitope spreading among others. In this review, we examine the data available for the involvement of viral infections in triggering or exacerbating autoimmune diseases in addition to discussing the mechanisms by which these viral infections and the immune pathways they trigger possibly contribute to the development of autoimmunity.
CASE STUDY OF CIRCADIAN RHYTHM SLEEP DISORDER FOLLOWING HALOPERIDOL TREATMENT: REVERSAL BY RISPERIDONE AND MELATONIN

A patient with Gilles de la Tourette syndrome treated with haloperidol, ingested once daily after awakening from sleep, exhibited an irregular sleep–wake pattern with a free-running component of approximately 48 h. Transfer to risperidone, ingested once daily after awakening from sleep, was beneficial resulting in a sleep–wake cycle more synchronized at the appropriate phase to the external zeitgebers, and fewer nocturnal disturbances. The circadian sleep–wake schedule was fully synchronized when the patient had been subsequently treated with melatonin at 21:00h, before intended nocturnal sleep, in addition to risperidone in the morning. Restoration of the sleep–wake circadian pattern was accompanied by the patient's subjective report of significant improvement in his quality of life, social interactions, and occupational status. This observation suggests that circadian rhythm sleep disorders can be related to the typical neuroleptic haloperidol and restored by the atypical neuroleptic risperidone. Similar findings reported in patients suffering from other disorders support the hypothesis that the described disruption of the sleep–wake schedule is medication rather than illness-related. Therefore, it is very important to realize that circadian rhythm sleep disorders may be a side effect of neuroleptics.
Exercise-Induced Muscle Damage and Recovery in Young and Middle-Aged Males with Different Resistance Training Experience

This study compared the time course of recovery after a squatting exercise in trained young (YG; n = 9; age 22.3 ± 1.7 years) and trained (MT; n = 9; 39.9 ± 6.2 years) and untrained (MU; n = 9; age 44.4 ± 6.3 years) middle-aged males. Before and at 24 and 72 h after 10 × 10 squats at 60% one-repetition maximum (1RM), participants provided measurements of perceived muscle soreness (VAS), creatine kinase (CK), maximal voluntary contraction (MVC), voluntary activation (VA), and resting doublet force of the knee extensors and squatting peak power at 20% and 80% 1RM. When compared to the YG males, the MT experienced likely and very likely moderate decrements in MVC, resting doublet force, and peak power at 20% and 80% 1RM accompanied by unclear differences in VAS, CK, and VA after the squatting exercise. MU males, compared to MT, experienced greater alterations in peak power at 20% and 80% 1RM and VAS. Alterations in CK, MVC, VA, and resting doublet force were unclear at all time-points between the middle-aged groups. Middle-aged males experienced greater symptoms of muscle damage and an impaired recovery profile than young resistance trained males. Moreover, regardless of resistance training experience, middle-aged males are subject to similar symptoms after muscle-damaging lower-body exercise.
Surface-Enhanced Raman Spectroscopy in Cancer Diagnosis, Prognosis and Monitoring

As medicine continues to advance our understanding of and knowledge about the complex and multifactorial nature of cancer, new major technological challenges have emerged in the design of analytical methods capable of characterizing and assessing the dynamic heterogeneity of cancer for diagnosis, prognosis and monitoring, as required by precision medicine. With this aim, novel nanotechnological approaches have been pursued and developed for overcoming intrinsic and current limitations of conventional methods in terms of rapidity, sensitivity, multiplicity, non-invasive procedures and cost. Eminently, a special focus has been put on their implementation in liquid biopsy analysis. Among optical nanosensors, those based on surface-enhanced Raman scattering (SERS) have been attracting tremendous attention due to the combination of the intrinsic prerogatives of the technique (e.g., sensitivity and structural specificity) and the high degree of refinement in nano-manufacturing, which translate into reliable and robust real-life applications. In this review, we categorize the diverse strategic approaches of SERS biosensors for targeting different classes of tumor biomarkers (cells, nucleic acids and proteins) by illustrating key recent research works. We will also discuss the current limitations and future research challenges to be addressed to improve the competitiveness of SERS over other methodologies in cancer medicine.
Helium-Induced Changes in Circulating Caveolin in Mice Suggest a Novel Mechanism of Cardiac Protection

The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) inhaled either He gas or adjusted room air. Functional measurements were performed in the isolated Langendorff perfused heart at 24 h post He inhalation. Electron paramagnetic resonance spectrometry (EPR) of samples was carried out at 24 h post He inhalation. Immunoblotting was used to detect Cav-1/3 expression in whole-heart tissue, exosomes isolated from platelet free plasma (PFP) and membrane fractions. Additionally, transmission electron microscopy analysis of cardiac tissue and serum function and metabolomic analysis were performed. In contrast to cardioprotection observed in in vivo models, the isolated Langendorff perfused heart revealed no protection after He inhalation. However, levels of Cav-1/3 were reduced 24 h after He inhalation in whole-heart tissue, and Cav-3 was increased in exosomes from PFP. Addition of serum to muscle cells in culture or naïve ventricular tissue increased mitochondrial metabolism without increasing reactive oxygen species generation. Primary and lipid metabolites determined potential changes in ceramide by He exposure. In addition to direct effects on myocardium, He likely induces the release of secreted membrane factors enriched in caveolae. Our results suggest a critical role for such circulating factors in He-induced organ protection.
Radical prostatectomy for high-risk prostate cancer | Opinion: YES

1 UroScience, Pontifícia Universidade de Campinas PUC, Campinas, SP, Brasil; 2 Departamento de Urologia, Universidade Estadual de Campinas UNICAMP, Campinas, SP, Brasil; 3 Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA ________________________________________________________________________________________
Is low‐level HIV‐1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

The clinical significance of low‐level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV‐positive adults in relation to LLV or permanent virological suppression during long‐term ART.
Optic Nerve Degeneration in Experimental Autoimmune Encephalomyelitis

The mechanisms of axonal and neuronal degeneration causing disability in optic neuritis and multiple sclerosis are poorly understood. Here we describe the role of mitochondria, oxidative stress and the effects of modulating antioxidant gene expression in the optic nerves of mice induced with experimental autoimmune encephalomyelitis, with a focus on long-term neuroprotection. Oxidative injury to the mitochondrion began prior to inflammatory cell infiltration and continued. It affected subunits of the respiratory chain, glycolysis and a chaperone critical to the stabilization and import of proteins. Oxidative products were associated with loss of membrane potential, mitochondrial degeneration and severe axonal loss. Reductions in ATP synthesis were even greater than those associated with mitochondrial diseases. Increasing SOD2 levels by viral mediated gene transfer rescued ATP synthesis, suppressed myelin fiber injury and increased retinal ganglion cell survival 1 year later.
A novel therapeutic peptide targeting myocardial reperfusion injury.

AIMS Regulated cell death is a main contributor of myocardial ischemia-reperfusion injury during acute myocardial infarction. In this context, targeting apoptosis could be a potent therapeutical strategy. In a previous study, we showed that DAXX (death-associated protein) was essential for transducing the FAS-dependent apoptotic signal during IR injury. The present study aims at evaluating the cardioprotective effects of a synthetic peptide inhibiting FAS:DAXX interaction. METHODS AND RESULTS An interfering peptide was engineered and then coupled to the Tat cell penetrating peptide (Tat-DAXXp). Its internalization and anti-apoptotic properties were demonstrated in primary cardiomyocytes. Importantly, an intravenous bolus injection of Tat-DAXXp (1 mg/kg) 5 min before reperfusion in a murine myocardial ischemia-reperfusion model decreased infarct size by 48% after 24 h of reperfusion. In addition, Tat-DAXXp was still efficient after a 30-min delayed administration, and was completely degraded and eliminated within 24 h thereby reducing risks of potential side effects. Importantly, Tat-DAXXp reduced mouse early post-infarction mortality by 67%. Mechanistically, cardioprotection was supported by both anti-apoptotic and pro-survival effects, and an improvement of myocardial functional recovery as evidenced in ex vivo experiments. CONCLUSIONS Our study demonstrates that a single dose of Tat-DAXXp injected intravenously at the onset of reperfusion leads to a strong cardioprotection in vivo by inhibiting ischemia-reperfusion injury validating Tat-DAXXp as a promising candidate for therapeutic application.
In ovo injection of flavanone on bone quality characteristics, biochemical parameters and antioxidant enzyme status of blood in daily chicks.

In ovo injection (IOI) of Naringin (N), flavanone was examined on post-hatch blood biochemical parameters, antioxidant status and bone characteristics. Fertile eggs (n = 700) were distributed in seven groups with 100 eggs. On 14th and 17.5th days of incubation, four groups were injected using 15 or 30 mg active ingredient levels of naringin/0.5 ml saline/egg, low and high level, into amnion sac. Controls include sham (injected normal saline, 0.5 ml/egg on day 14 and 17.5th) and un-injected group. IOI of high naringin and saline on 14th day of incubation resulted in lower hatchability and then higher mortality in last week of embryonic life. On day hatch, high levels of injected groups more body weight compared to the control. Chick length was increased at high levels of naringin on day 17.5th compared to control and saline injected. Quality traits of bones were improved in naringin-injected groups compared to control. IOI of naringin influenced thyroid hormones on 14th day of incubation. Naringin groups influenced the Alkaline phosphatase (ALP), Calcium (Ca), superoxide dismutase (SOD), blood biochemical and lipids. Totally, amniotic IOI of naringin in last days of developing embryo may be useful for hatched chick, development of leg long bone or effect on biochemical metabolites by levels of flavanone that it needs more research.
Lack of effectiveness of combined 5‐fluorouracil and methyl‐ccnu therapy in advanced colorectal cancer

Fifty‐two patients with advanced colorectal cancer were treated with a combination of 5‐Fluorouracil (FU) plus methyl‐1,3‐cis (2‐chlorethyl)‐1‐nitrosourea (MeCCNU). The treatment schedule program consisted of 5‐FU, 300 mg/m2 i.v. bolus, daily for 5 days, repeated at 5‐week cycles. MeCCNU was administered at a dose of 150 mg/m2 orally on day 1 of the initial 5‐day course of FU and repeated at 10‐week intervals. Eighty‐four percent (44/52) of the patients with advanced measurable disease developed progressive disease by 4 months or one and a half cycles of therapy. Only two patients had definite partial regression of tumor over the period of observation. The median survival of all patients measured from the onset of treatment was 9 months and is comparable to literature reports of untreated advanced colorectal cancer. This therapeutic trial of combined FU and MeCCNU, employing a dose‐schedule distinct from but comparable to previous studies has failed to confirm the substantial response rate reported by other investigators and reinforces the need for exploring new drugs and combinations of drugs in advanced colorectal cancer. The use of sequential plasma CEA determinations as a primary monitor of therapy is discussed in relationship to clinical trials and guidelines for determining significant quantitative changes in plasma CEA levels are recommended. Cancer 40:2792‐2796, 1977.
Willingness to Participate in Hypothetical HIV Vaccine Trial and Associated Factors among People Who Inject Drugs in Dar es Salaam, Tanzania

This study is aimed at assessing the willingness to participate in the HIV vaccine trials and the associated factors among people who inject drugs (PWIDs) in Tanzania. Information about the willingness to participate and the associated factors was collected using interviewer-administered questionnaires at the medication treatment for opioid use disorder (MOUD) clinic in Dar es Salaam. Data analysis was performed using the IBM SPSS Statistic 20. The mean age of respondents was 36.7, and the standard deviation (SD) was ±7.2. The majority of respondents (68%) had primary education, and a high proportion of them were single (61.5%). More than one-third (37.9%) shared needles and syringes. Most (87.3%) had more than three sexual partners, and almost half (51.4%) did not use condoms during sexual intercourse with nonregular partners. About 63% had knowledge of HIV transmission while 27% had heard about HIV vaccine trials. Generally, 76% of the respondents expressed willingness to participate in future HIV vaccine trials regardless of prior knowledge of HIV vaccine trials. Willingness to participate in HIV vaccine trials was not associated with education level, people living with, knowledge about HIV transmission, awareness of HIV vaccine trials, sharing of syringe/needles, and number of sexual partners. Only older age (OR = 1.6, 95%CI = 1.01, 2.6) and condom use (OR = 0.49, 95%CI = 0.26, 0.97) showed an association with willingness. However, after performing logistic regression with factors at p value ≤ 0.2 to ascertain the other factors on the effects of age, condom use, education level, and sharing of needles/syringes, the results were not statistically significant. Although participants reported a high willingness to participate in hypothetical HIV vaccine trials, no definitive conclusion can be drawn about the associated factors. Further studies with intensive educational programs are needed to investigate the factors on willingness to participate in actual HIV vaccine trials among PWIDs.