Takshan/R1 huggingface dataset:
Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study.

BACKGROUND: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. METHODS: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. RESULTS: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n = 5), breast (n = 8), other skin sites (n = 3), and soft tissue (n = 3). Target lesions (n = 54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). CONCLUSIONS: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas. J. Surg. Oncol. 2016;114:246-253. © 2016 Wiley Periodicals, Inc.
Videoscopic ilioinguinal lymphadenectomy for groin lymph node metastases from melanoma.

BACKGROUND: Groin lymph node dissection for melanoma is burdened by high postoperative morbidity. Videoscopic lymphadenectomy may lower the incidence of complications, including infection, dehiscence and lymphoedema. This pilot study aimed to investigate the feasibility and postoperative outcomes of videoscopic ilioinguinal lymphadenectomy in patients with inguinal nodal melanoma metastases. METHODS: Patients with inguinal nodal metastases, with either a positive sentinel lymph node biopsy or clinically positive nodes from melanoma, were enrolled. Inguinal dissection was performed via three ports. Iliac dissection was obtained through a preperitoneal access. Intraoperative and postoperative data were collected. RESULTS: Of 23 patients selected for 24 procedures, four needed conversion to an open procedure. Median duration of surgery was 270 (i.q.r. 245-300) min. Wound-related postoperative complications occurred in four patients, although only one needed further intervention. The median number of excised lymph nodes was 21 (i.q.r. 15-25). After a median follow-up of 18 months, regional lymph node recurrence was observed in two patients. CONCLUSION: Videoscopic ilioinguinal lymphadenectomy for melanoma groin lymph node metastases is technically feasible, safe, and associated with acceptable morbidity and oncological outcome.
Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review.

BACKGROUND: Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on electrochemotherapy. METHODS: The quality of reporting in published studies on electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. RESULTS: A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on electrochemotherapy were prepared and summarized into a checklist. CONCLUSIONS: There is an increasing body of published clinical data on electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice.
Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin.

Neuronal accumulation of UBB(+1), a frameshift variant of ubiquitin B, is a hallmark of Alzheimer's disease (AD). How UBB(+1) contributes to neuronal dysfunction remains elusive. Here, we show that in brain regions of AD patients with neurofibrillary tangles UBB(+1) co-exists with VMS1, the mitochondrion-specific component of the ubiquitin-proteasome system (UPS). Expression of UBB(+1) in yeast disturbs the UPS, leading to mitochondrial stress and apoptosis. Inhibiting UPS activity exacerbates while stimulating UPS by the transcription activator Rpn4 reduces UBB(+1)-triggered cytotoxicity. High levels of the Rpn4 target protein Cdc48 and its cofactor Vms1 are sufficient to relieve programmed cell death. We identified the UBB(+1)-induced enhancement of the basic amino acids arginine, ornithine, and lysine at mitochondria as a decisive toxic event, which can be reversed by Cdc48/Vms1-mediated proteolysis. The fact that AD-induced cellular dysfunctions can be avoided by UPS activity at mitochondria has potentially far-reaching pathophysiological implications.
The Affordability of Providing Sexually Transmitted Disease Services at a Safety-net Clinic.

INTRODUCTION: Sexually transmitted diseases continue to increase in the U.S. There is a growing need for financially viable models to ensure the longevity of safety-net sexually transmitted disease clinics, which provide testing and treatment to high-risk populations. This micro-costing analysis estimated the number of visits required to balance cost and revenue of a sexually transmitted disease clinic in a Medicaid expansion state. METHODS: In 2017, actual and projected cost and revenues were estimated from the Rhode Island sexually transmitted disease clinic in 2015. Projected revenues for a hypothetical clinic offering a standard set of sexually transmitted disease services were based on Medicaid; private ("commercial") insurance; and institutional ("list price") reimbursement rates. The number of visits needed to cover clinic costs at each rate was assessed. RESULTS: Total operating cost for 2,153 clinic visits was estimated at $255,769, or $119 per visit. Laboratory testing and salaries each accounted for 44% of operating costs, medications for treatment 7%, supplies 5%, and 28% of visits used insurance. For a standard clinic offering a basic set of sexually transmitted disease services to break even, a projected 73% of visits need to be covered at the Medicaid rate, 38% at private rate, or 11% at institutional rate. CONCLUSIONS: Sexually transmitted disease clinics may be financially viable when a majority of visits are billed at a Medicaid rate; however, mixed private/public models may be needed if not all visits are billed. In this manner, sexually transmitted disease clinics can be solvent even if not all visits are billed to insurance, thus ensuring access to uninsured or underinsured patients.
Rationally Designed Vaccines Targeting the V2 Region of HIV-1 gp120 Induce a Focused, Cross-Clade-Reactive, Biologically Functional Antibody Response.

Strong antibody (Ab) responses against V1V2 epitopes of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope (Env) correlated with reduced infection rates in studies of HIV, simian-human immunodeficiency virus (SHIV), and simian immunodeficiency virus (SIV). In order to focus the Ab response on V1V2, we used six V1V2 sequences and nine scaffold proteins to construct immunogens which were tested using various immunization regimens for their ability to induce cross-reactive and biologically active V2 Abs in rabbits. A prime/boost immunization strategy was employed using gp120 DNA and various V1V2-scaffold proteins. The rabbit polyclonal Ab responses (i) were successfully focused on the V1V2 region, with weak or only transient responses to other Env epitopes, (ii) displayed broad cross-reactive binding activity with gp120s and the V1V2 regions of diverse strains from clades B, C, and E, (iii) included V2 Abs with specificities similar to those found in HIV-infected individuals, and (iv) remained detectable ≥1 year after the last boosting dose. Importantly, sera from rabbits receiving V1V2-scaffold immunogens displayed Ab-dependent cellular phagocytosis whereas sera from rabbits receiving only gp120 did not. The results represent the first fully successful example of reverse vaccinology in the HIV vaccine field with rationally designed epitope scaffold immunogens inducing Abs that recapitulate the epitope specificity and biologic activity of the human monoclonal Abs from which the immunogens were designed. Moreover, this is the first immunogenicity study using epitope-targeting, rationally designed vaccine constructs that induced an Fc-mediated activity associated with protection from infection with HIV, SIV, and SHIV. IMPORTANCE: Novel immunogens were designed to focus the antibody response of rabbits on the V1V2 epitopes of HIV-1 gp120 since such antibodies were associated with reduced infection rates of HIV, SIV, and SHIV. The vaccine-induced antibodies were broadly cross-reactive with the V1V2 regions of HIV subtypes B, C and E and, importantly, facilitated Fc-mediated phagocytosis, an activity not induced upon immunization of rabbits with gp120. This is the first immunogenicity study of vaccine constructs that focuses the antibody response on V1V2 and induces V2-specific antibodies with the ability to mediate phagocytosis, an activity that has been associated with protection from infection with HIV, SIV, and SHIV.
Communities in charge of alcohol (CICA): a protocol for a stepped-wedge randomised control trial of an alcohol health champions programme.

BACKGROUND: Communities In Charge of Alcohol (CICA) takes an Asset Based Community Development (ABCD) approach to reducing alcohol harm. Through a cascade training model, supported by a designated local co-ordinator, local volunteers are trained to become accredited 'Alcohol Health Champions' to provide brief opportunistic advice at an individual level and mobilise action on alcohol availability at a community level. The CICA programme is the first time that a devolved UK region has attempted to coordinate an approach to building health champion capacity, presenting an opportunity to investigate its implementation and impact at scale. This paper describes the protocol for a stepped wedge randomised controlled trial of an Alcohol Health Champions programme in Greater Manchester which aims to strengthen the evidence base of ABCD approaches for health improvement and reducing alcohol-related harm. METHODS: A natural experiment that will examine the effect of CICA on area level alcohol-related hospital admissions, Accident and Emergency attendances, ambulance call outs, street-level crime and anti-social behaviour data. Using a stepped wedged randomised design (whereby the intervention is rolled out sequentially in a randomly assigned order), potential changes in health and criminal justice primary outcomes are analysed using mixed-effects log-rate models, differences-in-differences models and Bayesian structured time series models. An economic evaluation identifies the set-up and running costs of CICA using HM Treasury approved standardised methods and resolves cost-consequences by sector. A process evaluation explores the context, implementation and response to the intervention. Qualitative analyses utilise the Framework method to identify underlying themes. DISCUSSION: We will investigate: whether training lay people to offer brief advice and take action on licensing decisions has an impact on alcohol-related harm in local areas; the cost-consequences for health and criminal justice sectors, and; mechanisms that influence intervention outcomes. As well as providing evidence for the effectiveness of this intervention to reduce the harm from alcohol, this evaluation will contribute to broader understanding of asset based approaches to improve public health. TRIAL REGISTRATION: ISRCTN 81942890 , date of registration 12/09/2017.
Medicine-related beliefs predict attribution of symptoms to a sham medicine: A prospective study.

OBJECTIVES: To investigate a range of possible predictors of nocebo responses to medicines. DESIGN: Prospective cohort study. METHODS: In total, 203 healthy adult volunteers completed measures concerning demographics, psychological factors, medicine-related beliefs, baseline symptoms, and symptom expectations before taking a sham pill, described as 'a well-known tablet available without prescription' that was known to be associated with several side effects. Associations between these measures and subsequent attribution of symptoms to the tablet were assessed using a hurdle model consisting of a joint logistic and truncated negative binomial regression. RESULTS: Men had an increased odds of attributing symptoms to the tablet OR = 1.52, and older participants had decreased odds, OR = 0.97. Medicine-related beliefs were important, with modern health worries, belief that medicines cause harm and perceived sensitivity to medicines associated with increased odds of symptom attribution, OR = 1.02, 1.10, 1.09, respectively. Trust in medicines and pharmaceutical companies decreased the odds of symptom attribution, OR = 0.91, 0.88, respectively. The number of symptoms at baseline and the expected likelihood of symptoms were associated with an increased odds of attributing symptoms to the tablet, OR = 1.07, 1.06, respectively. Anxiety, previous symptom experience, symptom expectations, and modern health worries were also important in predicting the number of symptoms participants attributed to the tablet. CONCLUSION: It is hard to predict who is at risk of developing nocebo responses to medicines from demographic or personality characteristics. Context-specific factors such as beliefs about and trust in medicines, current symptoms and symptom expectations are more useful as predictors. More work is needed to investigate this in a patient sample. Statement of contribution What is already known on this subject? Many patients report non-specific side effects to their medication which may arise through a nocebo effect. Whether some people are particularly predisposed to experience nocebo effects remains unclear. What does this study add? Demographic and personality characteristics are poor predictors of symptom attribution to a sham medicine. Instead, context-specific factors that concern people's beliefs surrounding medicines, their current symptoms, and symptom expectations are more useful as predictors of symptom attribution.
Metal-organic frameworks as selectivity regulators for hydrogenation reactions.

Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them from α,β-unsaturated aldehydes, through the selective hydrogenation of the carbon-oxygen group (in preference to the carbon-carbon group). However, developing effective catalysts for this transformation is challenging, because hydrogenation of the carbon-carbon group is thermodynamically favoured. This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not. This has inspired the use of metal-organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material. Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of α,β-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe(3+), Cr(3+) or both (known as MIL-101; refs 19, 20, 21) results in stable catalysts that convert a range of α,β-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon-oxygen rather than the carbon-carbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.
3D printing the pterygopalatine fossa: a negative space model of a complex structure.

PURPOSE: The pterygopalatine fossa is one of the most complex anatomical regions to understand. It is poorly visualized in cadaveric dissection and most textbooks rely on schematic depictions. We describe our approach to creating a low-cost, 3D model of the pterygopalatine fossa, including its associated canals and foramina, using an affordable "desktop" 3D printer. METHODS: We used open source software to create a volume render of the pterygopalatine fossa from axial slices of a head computerised tomography scan. These data were then exported to a 3D printer to produce an anatomically accurate model. RESULTS: The resulting 'negative space' model of the pterygopalatine fossa provides a useful and innovative aid for understanding the complex anatomical relationships of the pterygopalatine fossa. CONCLUSION: This model was designed primarily for medical students; however, it will also be of interest to postgraduates in ENT, ophthalmology, neurosurgery, and radiology. The technical process described may be replicated by other departments wishing to develop their own anatomical models whilst incurring minimal costs.
Relationship between preoperative axial length and myopic shift over 3 years after congenital cataract surgery with primary intraocular lens implantation at the National Institute of Ophthalmology of Peru, 2007-2011.

Objective: To determine the relationship between the preoperative axial length and the myopic shift over 3 years after congenital cataract surgery with primary intraocular lens implantation and other related factors. Methods: In this retrospective cohort study, the axial length was measured and assigned into 2 groups (>21.5 mm and ≤21.5 mm), visual axis obscuration, laterality of cataract, age of surgery and follow-up time were assessed and compared to the myopic shift. Results: The mean myopic shift was 3.6 (standard deviation [SD]: 2.3) diopters (D) in all patients; 3.2 (3.3) and 3.9 (3.2) D for each group respectively (p=0.359). In unilateral cataracts the mean myopic shift was 6.3 D and in bilateral cases was 3.0 D (p=0.001). In bilateral cataracts, the shift was 2.6 D (SD: 2.0) and 3.4 D (SD: 1.8), respectively (p=0.098). Conclusion: There was no relationship between the initial axial length and the myopic shift in all patients. Unilateral cataracts had a greater myopic shift over 3 years.
Altered reward system reactivity for personalized circumscribed interests in autism.

Background: Neurobiological research in autism spectrum disorders (ASD) has paid little attention on brain mechanisms that cause and maintain restricted and repetitive behaviors and interests (RRBIs). Evidence indicates an imbalance in the brain's reward system responsiveness to social and non-social stimuli may contribute to both social deficits and RRBIs. Thus, this study's central aim was to compare brain responsiveness to individual RRBI (i.e., circumscribed interests), with social rewards (i.e., social approval), in youth with ASD relative to typically developing controls (TDCs). Methods: We conducted a 3T functional magnetic resonance imaging (fMRI) study to investigate the blood-oxygenation-level-dependent effect of personalized circumscribed interest rewards versus social rewards in 39 youth with ASD relative to 22 TDC. To probe the reward system, we employed short video clips as reinforcement in an instrumental incentive delay task. This optimization increased the task's ecological validity compared to still pictures that are often used in this line of research. Results: Compared to TDCs, youth with ASD had stronger reward system responses for CIs mostly within the non-social realm (e.g., video games) than social rewards (e.g., approval). Additionally, this imbalance within the caudate nucleus' responsiveness was related to greater social impairment. Conclusions: The current data support the idea of reward system dysfunction that may contribute to enhanced motivation for RRBIs in ASD, accompanied by diminished motivation for social engagement. If a dysregulated reward system indeed supports the emergence and maintenance of social and non-social symptoms of ASD, then strategically targeting the reward system in future treatment endeavors may allow for more efficacious treatment practices that help improve outcomes for individuals with ASD and their families.