Miracle-dz/UniFAR-FTUs huggingface dataset:
Cowden disease and Lhermitte-Duclos disease: an update. Case report and review of the literature.

OBJECT Cowden disease is a rare autosomal-dominant phacomatosis and cancer syndrome that is associated with Lhermitte-Duclos disease (LDD), also called dysplastic cerebellar gangliocytoma. METHODS In this review the authors summarize the additions to the literature during the past 5 years, with emphasis on new case reports and advances in imaging and molecular biology. Adult-onset LDD is now considered pathognomonic for Cowden disease. Approximately 220 cases of LDD have been reported. Magnetic resonance imaging in patients with LDD is often diagnostic, and imaging studies have facilitated accurate diagnosis and contributed to the improved outcome in affected patients. Cowden disease and other rare, related disorders, such as Bannayan-Riley-Ruvalcaba, Proteus, and Proteus- like syndromes, are often caused by mutations of the PTEN gene. CONCLUSIONS Because of the high incidence of systemic cancer in patients with Cowden disease, it is important for neurosurgeons to recognize the association between this disease and LDD and to refer affected patients for appropriate cancer screenings and interventions.
Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells

ABSTRACT The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines. Immune response was evaluated by delayed-type hypersensitivity (DTH), T cell proliferation and cytokine assays. Data were collected for 10 y after inclusion of the last patient. No serious adverse events were detected. In the intention-to-treat-cohort, we demonstrated significantly superior survival compared to matched controls from a benchmark meta-analysis (1 y survival 43% vs. 24%, 2 y 23% vs. 6.6%). A tumor-specific immune response was demonstrated in 16/31 patients. The response rate was higher after intradermal than intranodal vaccination (80% vs. 38%). Immune responders had improved survival compared to non-responders (median 14 mo vs. 6 mo; p = 0.030), and all eight patients surviving >20 mo were immune responders. In addition to the tumor-specific response, most patients developed a response against autologous DC antigens. The cytokine profile was polyfunctional and did not follow a Th1/Th2 dichotomy. We conclude that the favorable safety profile and evidence of a possible survival benefit warrant further studies of the RNA/DC vaccine. The vaccine appears insufficient as monotherapy, but there is a strong rationale for combination with checkpoint modulators.
Ketamine suppresses endotoxin‐induced NF‐κB activation and cytokines production in the intestine

Background: Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. However, ketamine also suppresses serum levels of endotoxin‐induced tumor necrosis factor‐alpha, and reduces mortality in mice in endotoxin shock. Our study was designed to investigate the protective effect of ketamine on the endotoxin‐induced proinflammatory cytokines and nuclear factor kappa B (NF‐κB) activation in vivo.
Prediction-Based Multi-Agent Reinforcement Learning in Inherently Non-Stationary Environments

Multi-agent reinforcement learning (MARL) is a widely researched technique for decentralised control in complex large-scale autonomous systems. Such systems often operate in environments that are continuously evolving and where agents’ actions are non-deterministic, so called inherently non-stationary environments. When there are inconsistent results for agents acting on such an environment, learning and adapting is challenging. In this article, we propose P-MARL, an approach that integrates prediction and pattern change detection abilities into MARL and thus minimises the effect of non-stationarity in the environment. The environment is modelled as a time-series, with future estimates provided using prediction techniques. Learning is based on the predicted environment behaviour, with agents employing this knowledge to improve their performance in realtime. We illustrate P-MARL’s performance in a real-world smart grid scenario, where the environment is heavily influenced by non-stationary power demand patterns from residential consumers. We evaluate P-MARL in three different situations, where agents’ action decisions are independent, simultaneous, and sequential. Results show that all methods outperform traditional MARL, with sequential P-MARL achieving best results.
Temporal bone chondroblastoma: big and small

Abstract Chondroblastoma represents approximately one per cent of all primary bone tumours. It is even rarer in the temporal bone and so far only 34 cases have been reported. We report here two cases with chondroblastoma of the temporal bone. The first case was discovered as a small lesion of the attic and root of zygoma. It was removed via mastoidectomy and reconstruction of the bony defect achieved normal external ear canal anatomy and hearing post-operatively. The second case presented as an advanced tumour involving the infratemporal fossa and parapharyngeal space. It was treated surgically via the infratemporal fossa approach. As clear surgical margins were not obtained, post-operative radiotherapy was also given to minimize the chance of recurrence.
CME Information : The Aggressive Peripheral T-Cell Lymphomas : 20151

No commercial support has been accepted related to the development or publication of this activity. CME Editor: Ayalew Tefferi, M.D. has no relevant financial relationships to disclose. Authors: James O. Armitage, M.D. discloses consultant fees received from Celgene, Conatus IDMC, GlaxoSmithKline DMC, Spectrum, and Ziopharm; as well as BOD Membership at Tesaro Bio, Inc. This activity underwent peer review in line with the standards of editorial integrity and publication ethics maintained by American Journal of Hematology. The peer reviewers have no conflicts of interest to disclose. The peer review process for American Journal of Hematology is single blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review. Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services’s Policy on Activity Disclosure and Conflict of Interest. The primary resolution method used was peer review and review by a non-conflicted expert.
Pain Threshold Is Achieved at Intensity Above Anaerobic Threshold in Patients With Intermittent Claudication

PURPOSE Walking training is considered as the first treatment option for patients with peripheral arterial disease and intermittent claudication (IC). Walking exercise has been prescribed for these patients by relative intensity of peak oxygen uptake (VO2peak), ranging from 40% to 70% VO2peak, or pain threshold (PT). However, the relationship between these methods and anaerobic threshold (AT), which is considered one of the best metabolic markers for establishing training intensity, has not been analyzed. Thus, the aim of this study was to compare, in IC patients, the physiological responses at exercise intensities usually prescribed for training (% VO2peak or % PT) with the ones observed at AT. METHODS Thirty-three IC patients performed maximal graded cardiopulmonary treadmill test to assess exercise tolerance. During the test, heart rate (HR), VO2, and systolic blood pressure were measured and responses were analyzed at the following: 40% of VO2peak; 70% of VO2peak; AT; and PT. RESULTS Heart rate and VO2 at 40% and 70% of VO2peak were lower than those at AT (HR: −13 ± 9% and −3 ± 8%, P < .01, respectively; VO2: −52 ± 12% and −13 ± 15%, P < .01, respectively). Conversely, HR and VO2 at PT were slightly higher than those at AT (HR: +3 ± 8%, P < .01; VO2: +6 ± 15%, P = .04). None of the patients achieved the respiratory compensation point. CONCLUSION Prescribing exercise for IC patients between 40% and 70% of VO2peak will induce a lower stimulus than that at AT, whereas prescribing exercise at PT will result in a stimulus above AT. Thus, prescribing exercise training for IC patients on the basis of PT will probably produce a greater metabolic stimulus, promoting better cardiovascular benefits.
Generation Difficulty and Memory for Source

The role of the word predictability from sentence context for reality monitoring and external source monitoring was examined in two experiments. In a reality-monitoring task, discrimination of an internal source was better in the hard than in the easy condition. It is probable that extra cognitive operations engaged during word generation in the hard condition were effective cues for reality-monitoring judgements. In contrast, in an external source-monitoring task (recognition memory of item's colour), the hard condition resulted in worse source memory for generated words than did the easy condition. This result is consistent both with an item–context trade-off hypothesis and a processing hypothesis. Greater effort involved at the time of generation might limit resources available for encoding of an external source. It is also possible that for generated words, the hard condition promoted conceptual processing instead of perceptual processing; therefore the item's colour was not effectively encoded.
Internalization-Dependent and -Independent Requirements for Transforming Growth Factor β Receptor Signaling via the Smad Pathway

ABSTRACT Members of the transforming growth factor β (TGF-β) family of proteins signal through cell surface transmembrane serine/threonine protein kinases known as type I and type II receptors. The TGF-β signal is extended through phosphorylation of receptor-associated Smad proteins by the type I receptor. Although numerous investigations have established the sequence of events in TGF-β receptor (TGF-βR) activation, none have examined the role of the endocytic pathway in initiation and/or maintenance of the signaling response. In this study we investigated whether TGF-βR internalization modulates type I receptor activation, the formation of a functional receptor/Smad/SARA complex, Smad2/3 phosphorylation or nuclear translocation, and TGF-β-dependent reporter gene activity. Our data provide evidence that, whereas type I receptor phosphorylation and association of SARA and Smad2 with the TGF-βR complex take place independently of clathrin lattice formation, Smad2 or Smad3 activation and downstream signaling only occur after endocytic vesicle formation. Thus, TGF-βR endocytosis is not simply a way to dampen the signaling response but instead is required to propagate signaling via the Smad pathway.
Why do people use unsecure public wi-fi?: an investigation of behaviour and factors driving decisions

Public Wi-Fi networks are now widely available in many countries. Though undoubtedly convenient, such networks have potential security and privacy risks. The aim of this study was to understand if people are aware of those risks, and - if so - why they decide to take them. We set up an experimental free Wi-Fi network at 14 locations in central London, UK, for a period of 150 hours, and people connected most often to use instant messaging, search engines, and social networks, and sensitive data (such as name, date of birth, and sexual orientation) were transmitted. We subsequently investigated people's risk awareness and risk behaviour through semi-structured interviews with 14 participants, and an online scenario-based survey with 102 participants. The majority of participants said they would use public Wi-Fi under circumstances where the risks taken are not consistent with maximising utility. Female participants rated the risks associated with public Wi-Fi use, more highly - and yet more females than males said they would use them to save their data plans. These findings align with insights from behavioural economics, specifically the insight that people can misjudge risky situations and do not make decisions consistent with expected utility theory.
Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.

Purpose Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Methods Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. Results The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. Conclusions BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.
DNA Immunization with Minigenes: Low Frequency of Memory Cytotoxic T Lymphocytes and Inefficient Antiviral Protection Are Rectified by Ubiquitination

ABSTRACT Our previous studies have shown that isolated cytotoxic T lymphocyte (CTL), B-cell, and T-helper epitopes, for which we coined the term minigenes, can be effective vaccines; when expressed from recombinant vaccinia viruses, these short immunogenic sequences confer protection against a variety of viruses and bacteria. In addition, we have previously demonstrated the utility of DNA immunization using plasmids encoding full-length viral proteins. Here we combine the two approaches and evaluate the effectiveness of minigenes in DNA immunization. We find that DNA immunization with isolated minigenes primes virus-specific memory CTL responses which, 4 days following virus challenge, appear similar in magnitude to those induced by vaccines known to be protective. Surprisingly, this vigorous CTL response fails to confer protection against a normally lethal virus challenge, although the CTL appear fully functional because, along with their high lytic activity, they are similar in affinity and cytokine secretion to CTL induced by virus infection. However this DNA immunization with isolated minigenes results in a low CTL precursor frequency; only 1 in ∼40,000 T cells is epitope specific. In contrast, a plasmid encoding the same minigene sequences covalently attached to the cellular protein ubiquitin induces protective immunity and a sixfold-higher frequency of CTL precursors. Thus, we show that the most commonly employed criterion to evaluate CTL responses—the presence of lytic activity following secondary stimulation—does not invariably correlate with protection; instead, the better correlate of protection is the CTL precursor frequency. Recent observations indicate that certain effector functions are active in memory CTL and do not require prolonged stimulation. We suggest that these early effector functions of CTL, immediately following infection, are critical in controlling virus dissemination and in determining the outcome of the infection. Finally, we show that improved performance of the ubiquitinated minigenes most probably requires polyubiquitination of the fusion protein, suggesting that the enhancement results from more effective delivery of the minigene to the proteasome.
Field Reliability Influences Field Validity: Risk Assessments of Individuals Found Not Guilty by Reason of Insanity

Individuals acquitted as not guilty by reason of insanity (NGRI) are usually committed to psychiatric hospitals for treatment until they are considered suitable for conditional release back to the community. The clinical evaluations that inform conditional release decisions have rarely been studied but provide an ideal opportunity to examine the reliability and validity of complex evaluations in the field. For example, to what extent do forensic evaluators agree about an acquittee’s readiness for conditional release? And how accurate are their opinions? We reviewed 175 evaluation reports across 62 cases from Hawaii, which requires 3 separate evaluations from independent clinicians for each felony NGRI acquittee referred for conditional release evaluation. Evaluators agreed about an NGRI acquittee’s readiness for conditional release in only 53.2% of evaluations (&kgr; = .35). Courts followed the majority evaluator opinion in 79.3% of all cases but ruled in an opposite direction from the majority evaluator opinion in more than a third of cases in which evaluators disagreed. Evaluators accurately differentiated those conditionally released acquittees who remained in the community from those who were rehospitalized in 62.4% of cases. Among the 43 insanity acquittees who were ultimately released, evaluator agreement was significantly associated with rehospitalization within 3 years. When the evaluators unanimously agreed that conditional release was appropriate, only 34.5% were rehospitalized. When the evaluators disagreed, 71.4% were rehospitalized. Overall, results reveal poor agreement among independent evaluators in routine practice but suggest that opinions may be more accurate when evaluators agree than when they disagree.
A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.

BACKGROUND There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function. METHOD Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response. RESULTS Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated. CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation.
Compliance to self-monitoring of blood glucose among patients with type 2 diabetes mellitus and its influential factors: a real-world cross-sectional study based on the Tencent TDF-I blood glucose monitoring platform.

BACKGROUND To investigate the compliance to self-monitoring of blood glucose (SMBG) among patients with type 2 diabetes mellitus (T2DM) and its influential factors. METHODS The real-world SMBG use over 90 days among 415 T2DM patients were recorded by using a blood glucose monitoring platform (TDF-I, Tencent, China). Clinical features including age, sex, duration of diabetes, insulin treatment or not, and use of oral antidiabetic drugs were collected. Poor compliance was defined as the average frequency of weekly SMBG use over 90 days was below the criteria established by the physicians, and otherwise the patients were regarded as with good compliance. Factors affecting the SMBG compliance were analyzed by using independent sample t-test, Mann-Whitney U test, and multivariate logistic regression analysis. RESULTS Only 57.6% of patients in the study cohort had good compliance to SMBG. Multivariate logistic regression models showed that only the duration of T2DM and the use of oral antidiabetic agents were independently associated with SMBG compliance; more specifically, patients with longer course of disease had poorer SMBG compliance, and those had used oral antidiabetic agents had poorer SMBG compliance. CONCLUSIONS SMBG compliance in T2DM patients needs to be further improved. For patients with a longer course of disease and/or under oral antidiabetic medication, interventions such as patient education should be adopted to increase the SMBG compliance.
Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives

All Societies, AASLD, EASL, APASL and JSH, identify patients with cirrhosis as a target population for surveillance, with minor differences for additional categories of patients, such as chronic hepatitis B and hepatitis C patients with advanced fibrosis. According to AASLD, liver disease related to metabolic diseases including diabetes and obesity is a recognized target of screening, since those conditions have been causally related to HCC. All societies endorse radiological non‐invasive techniques as the mainstay for early diagnosis of HCC, but discrepancies exist between Societies on the utilization of contrast‐enhanced ultrasound and utilization of serum markers for surveillance and diagnosis of HCC. The diagnostic algorithm of the international societies differ substantially in the anatomic paradigm of EASL and APASL which identify 1 cm size as the starting point for radiological diagnosis of HCC compared to APASL algorithm based on the dynamic pattern of contrast imaging, independently on tumour size. While strengthening prediction in individual patients is expected to improve cost‐effectiveness ratios of screening, the benefits of pre‐treatment patient stratification by clinical, histological and genetic scores remain uncertain and exclusion of patients with severe co‐morbidities and advanced age is still debated.