Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality assurance of Cyberknife robotic stereotactic radiosurgery using an angularly independent silicon detector

Abstract Purpose The aim of this work was to evaluate the use of an angularly independent silicon detector (edgeless diodes) developed for dosimetry in megavoltage radiotherapy for Cyberknife in a phantom and for patient quality assurance (QA). Method The characterization of the edgeless diodes has been performed on Cyberknife with fixed and IRIS collimators. The edgeless diode probes were tested in terms of basic QA parameters such as measurements of tissue‐phantom ratio (TPR), output factor and off‐axis ratio. The measurements were performed in both water and water‐equivalent phantoms. In addition, three patient‐specific plans have been delivered to a lung phantom with and without motion and dose measurements have been performed to verify the ability of the diodes to work as patient‐specific QA devices. The data obtained by the edgeless diodes have been compared to PTW 60016, SN edge, PinPoint ionization chamber, Gafchromic EBT3 film, and treatment planning system (TPS). Results The TPR measurement performed by the edgeless diodes show agreement within 2.2% with data obtained with PTW 60016 diode for all the field sizes. Output factor agrees within 2.6% with that measured by SN EDGE diodes corrected for their field size dependence. The beam profiles’ measurements of edgeless diodes match SN EDGE diodes with a measured full width half maximum (FWHM) within 2.3% and penumbra widths within 0.148 mm. Patient‐specific QA measurements demonstrate an agreement within 4.72% in comparison with TPS. Conclusion The edgeless diodes have been proved to be an excellent candidate for machine and patient QA for Cyberknife reproducing commercial dosimetry device measurements without need of angular dependence corrections. However, further investigation is required to evaluate the effect of their dose rate dependence on complex brain cancer dose verification.
Overweight in midlife and risk of cancer in late life: A nationwide Swedish twin study

Our study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late‐life cancer risk and explored the role of genetic and early‐life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30–50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case–control data (controlled for the clustering of twins within a pair). A co‐twin matched case–control analysis used conditional logistic regression to compare cancer‐discordant twins. Of all participants, 3968 (26.9%) were overweight and 4253 (28.8%) had cancer. In multi‐adjusted GEE models using normal‐weight (BMI 18.5–24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00–1.84, p = 0.049), liver cancer (OR 2.00, 95% CI: 1.11–3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19–6.91) and corpus uteri cancer (OR 1.78, 95% CI: 1.14–2.78) but lower risk of nonmelanoma skin cancer (OR 0.77, 95% CI: 0.66–0.90). In conditional logistic regression analysis, these associations were attenuated becoming nonsignificance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late‐life colon, liver and uterine cancer but reduced risk of late‐life nonmelanoma skin cancer. Further investigations are warranted to explore the role of genetic and early‐life environmental factors in these associations.
Factors associated with disease progression in dogs with presumed preclinical degenerative mitral valve disease attending primary care veterinary practices in the United Kingdom

Background Factors associated with disease progression in dogs with preclinical (stage B) degenerative mitral valve disease (DMVD) have not been evaluated previously in primary care veterinary practice. Objectives To evaluate whether plasma cardiac biomarkers, clinical signs, and physical examination findings are associated with clinical progression (reaching the composite endpoint of initiation of treatment with a potent diuretic or cardiac death) in dogs presumed to have stage B DMVD. Animals Six‐hundred and eighty‐four dogs diagnosed with DMVD recruited from 73 primary care practices in the United Kingdom. Dogs were not receiving potent diuretics at recruitment. Methods Prospective cohort study design. Primary care veterinarians recorded the presence or absence of clinical signs and physical examination findings. Baseline plasma N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and cardiac troponin I were measured. Cox regression models measured associations between risk factor variables and clinical progression. Flexible parametric models generated predicted probabilities of reaching the composite endpoint for dogs with different combinations of prognostic risk factor variables. Results Plasma NT‐proBNP, heart rate, heart murmur intensity, presence of a cough, being a Cavalier King Charles Spaniel, and being prescribed pimobendan were associated with clinical progression to initiation of treatment with a potent diuretic or cardiac‐related death. Conclusions and Clinical Importance Dogs with stage B DMVD identified as having a high risk of disease progression might benefit from more frequent monitoring or further diagnostic evaluation. The prognostic factors identified could facilitate risk stratification of dogs presenting with preclinical DMVD.
Exploring General Practitioners’ Views and Experiences of Providing Care to People with Borderline Personality Disorder in Primary Care: A Qualitative Study in Australia

The prevalence of people seeking care for Borderline Personality Disorder (BPD) in primary care is four to five times higher than in the general population. Therefore, general practitioners (GPs) are important sources of assessment, diagnosis, treatment, and care for these patients, as well as important providers of early intervention and long-term management for mental health and associated comorbidities. A thematic analysis of two focus groups with 12 GPs in South Australia (in discussion with 10 academic, clinical, and lived experience stakeholders) highlighted many challenges faced by GPs providing care to patients with BPD. Major themes were: (1) Challenges Surrounding Diagnosis of BPD; (2) Comorbidities and Clinical Complexity; (3) Difficulties with Patient Behaviour and the GP–Patient Relationship; and (4) Finding and Navigating Systems for Support. Health service pathways for this high-risk/high-need patient group are dependent on the quality of care that GPs provide, which is dependent on GPs’ capacity to identify and understand BPD. GPs also need to be supported sufficiently in order to develop the skills that are necessary to provide effective care for BPD patients. Systemic barriers and healthcare policy, to the extent that they dictate the organisation of primary care, are prominent structural factors obstructing GPs’ attempts to address multiple comorbidities for patients with BPD. Several strategies are suggested to support GPs supporting patients with BPD.
Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.
Immigrants’ Economic Assimilation: Evidence from Longitudinal Earnings Records

We examine immigrants’ earnings trajectories and measure the extent and speed with which they are able to reduce the earnings gap with natives, using a dataset that links respondents of the Survey of Income and Program Participation (SIPP) to their longitudinal earnings obtained from individual tax records. Our analysis addresses key debates regarding ethnoracial and cohort differences in immigrants’ earnings trajectories. First, we find a racially differentiated pattern of earnings assimilation: black and Hispanic immigrants are less able to catch up with native whites’ earnings compared to white and Asian immigrants, but they are almost able to reach earnings parity with natives of their same race and ethnicity. Second, we find no evidence of a declining “quality” of immigrant cohorts even after controlling for their ethnoracial composition and human capital. Immigrants arriving since 1994 actually experience similar or slightly higher earnings growth compared to immigrants from earlier eras. We identify a pattern of accelerated assimilation in which more educated immigrants experience much of their earnings growth during the first years after arriving.
Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-κB and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-κB and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.
Acute Phase Treatment Outcomes of Electroconvulsive Therapy in Adolescents and Young Adults.

OBJECTIVE Electroconvulsive therapy (ECT) is a highly efficacious, well-tolerated treatment in adults. Little is known, however, about its effectiveness in adolescents and young adults. Our objectives were to assess clinical outcomes after acute phase ECT in adolescents and young adults and determine whether screening positive or negative for a substance use disorder (SUD) is associated with differences in treatment outcomes. METHODS Study sample consisted of all patients 16 to 25 years old who received ECT from May 2011 to August 2016 and who completed self-reported SUD screens and the Behavior and Symptom Identification Scale-24 (BASIS-24) initially and completed the BASIS-24 again after the fifth ECT treatment. For 5 BASIS-24 domains, longitudinal changes in mean domain scores were assessed; mean changes by SUD screening status were also examined using linear mixed models. RESULTS One hundred ninety adolescents and young adults, with mean age 21.0 ± 2.6 years, met inclusion criteria. Electroconvulsive therapy was associated with significant clinical improvement (score decreases) in all 5 BASIS-24 domains during the acute phase treatment (P < 0.001). Sixty-four percent (122/190) screened positive for SUD. Compared with adolescents and young adults screening negative for SUD, those screening positive for co-occurring SUD had greater improvement in depression/functioning (-0.37 ± 0.14, P = 0.009), interpersonal relationships (-0.27 ± 0.13, P = 0.045), and emotional lability (-0.27 ± 0.14, P = 0.044) domains after the fifth ECT treatment. CONCLUSIONS Electroconvulsive therapy in adolescents and young adults was associated with significantly improved clinical outcomes during acute phase treatment. Adolescents and young adults screening positive for SUD had better acute phase ECT outcomes in self-reported depression/functioning, interpersonal relationships, and emotional lability than those screening negative. More research is needed to clarify adolescents and young adult patient characteristics that may be associated with differential ECT outcomes.
Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy

Titin, the largest protein known, forms an elastic myofilament in the striated muscle sarcomere. To establish titin’s contribution to skeletal muscle passive stiffness, relative to that of the extracellular matrix, a mouse model was created in which titin’s molecular spring region was shortened by deleting 47 exons, the TtnΔ112-158 model. RNA sequencing and super-resolution microscopy predicts a much stiffer titin molecule. Mechanical studies with this novel mouse model support that titin is the main determinant of skeletal muscle passive stiffness. Unexpectedly, the in vivo sarcomere length working range was shifted to shorter lengths in TtnΔ112-158 mice, due to a ~ 30% increase in the number of sarcomeres in series (longitudinal hypertrophy). The expected effect of this shift on active force generation was minimized through a shortening of thin filaments that was discovered in TtnΔ112-158 mice. Thus, skeletal muscle titin is the dominant determinant of physiological passive stiffness and drives longitudinal hypertrophy. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Using a monotone single‐index model to stabilize the propensity score in missing data problems and causal inference

The augmented inverse weighting method is one of the most popular methods for estimating the mean of the response in causal inference and missing data problems. An important component of this method is the propensity score. Popular parametric models for the propensity score include the logistic, probit, and complementary log‐log models. A common feature of these models is that the propensity score is a monotonic function of a linear combination of the explanatory variables. To avoid the need to choose a model, we model the propensity score via a semiparametric single‐index model, in which the score is an unknown monotonic nondecreasing function of the given single index. Under this new model, the augmented inverse weighting estimator (AIWE) of the mean of the response is asymptotically linear, semiparametrically efficient, and more robust than existing estimators. Moreover, we have made a surprising observation. The inverse probability weighting and AIWEs based on a correctly specified parametric model may have worse performance than their counterparts based on a nonparametric model. A heuristic explanation of this phenomenon is provided. A real‐data example is used to illustrate the proposed methods.
Construction of Electrochemical Immunosensor Based on Gold-Nanoparticles/Carbon Nanotubes/Chitosan for Sensitive Determination of T-2 Toxin in Feed and Swine Meat

T-2 toxin (T-2) is one of major concern mycotoxins acknowledged as an unavoidable contaminant in human foods, animal feeds and also agriculture products. Thus, a facile and sensitive method is essential for accurate T-2 toxin detection. In our work, a specific electrochemical immunosensor based on gold nanoparticles/carboxylic group-functionalized single-walled carbon nanotubes/chitosan (AuNPs/cSWNTs/CS) composite was established. The mechanism of the electrochemical immunosensor was an indirect competitive binding to a given amount of anti-T-2 between free T-2 and T-2-bovine serum albumin, which was conjugated on covalently functionalized cSWNTs decorated on the glass carbon electrode. Afterwards, the alkaline phosphatase labeled anti-mouse secondary antibody was bound to the electrode surface by reacting with the primary antibody. Lastly, alkaline phosphatase catalyzed the hydrolysis of the substrate α-naphthyl phosphate, which produced an electrochemical signal. Compared with conventional methods, the established immunosensor was more sensitive and simpler. Under optimal conditions, this method could quantitatively detect T-2 from 0.01 to 100 μg·L−1 with a detection limit of 0.13 μg·L−1 and favorable recovery 91.42–102.49%. Moreover, the immunosensor was successfully applied to assay T-2 in feed and swine meat, which showed good correlation with the results obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Two main focal seizure patterns revealed by intracerebral electroencephalographic biomarker analysis

Long‐term recording with intracerebral electrodes is commonly utilized to identify brain areas responsible for seizure generation (epileptogenic zone) and to tailor therapeutic surgical resections in patients with focal drug‐resistant epilepsy. This invasive diagnostic procedure generates a wealth of data that contribute to understanding human epilepsy. We analyze intracerebral signals to identify and classify focal ictal patterns.
Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections

Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.
A Metabologenomic Approach Reveals Changes in the Intestinal Environment of Mice Fed on American Diet

Intestinal microbiota and their metabolites are strongly associated with host physiology. Developments in DNA sequencing and mass spectrometry technologies have allowed us to obtain additional data that enhance our understanding of the interactions among microbiota, metabolites, and the host. However, the strategies used to analyze these datasets are not yet well developed. Here, we describe an original analytical strategy, metabologenomics, consisting of an integrated analysis of mass spectrometry-based metabolome data and high-throughput-sequencing-based microbiome data. Using this approach, we compared data obtained from C57BL/6J mice fed an American diet (AD), which contained higher amounts of fat and fiber, to those from mice fed control rodent diet. The feces of the AD mice contained higher amounts of butyrate and propionate, and higher relative abundances of Oscillospira and Ruminococcus. The amount of butyrate positively correlated with the abundance of these bacterial genera. Furthermore, integrated analysis of the metabolome data and the predicted metagenomic data from Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) indicated that the abundance of genes associated with butyrate metabolism positively correlated with butyrate amounts. Thus, our metabologenomic approach is expected to provide new insights and understanding of intestinal metabolic dynamics in complex microbial ecosystems.