Miracle-dz/UniFAR-FTUs huggingface dataset:
Feasibility and limitations of bulk density assignment in MRI for head and neck IMRT treatment planning

Head and neck cancers centered at the base of skull are better visualized on MRI than on CT. The purpose of this investigation was to investigate the accuracy of bulk density assignment in head and neck intensity‐modulated radiation therapy (IMRT) treatment plan optimization. Our study investigates dose calculation differences between density‐assigned MRI and CT, and identifies potential limitations related to dental implants and MRI geometrical distortion in the framework of MRI‐only‐based treatment planning. Bulk density assignment was performed and applied onto MRI to generate three MRI image sets with increasing levels of heterogeneity for seven patients: 1) MRIW: all water‐equivalent; 2) MRIW + B: included bone with density of 1.53 g/cm3; and 3) MRIW + B + A: included bone and air. Using identical planning and optimization parameters, MRI‐based IMRT plans were generated and compared to corresponding, forward‐calculated, CT‐based plans on the basis of target coverage, isodose distributions, and dose‐volume histograms (DVHs). Phantom studies were performed to assess the magnitude and spatial dependence of MRI geometrical distortion. MRIW‐based dose calculations overestimated target coverage by 16.1%. Segmentation of bone reduced differences to within 2% of the coverage area on the CT‐based plan. Further segmentation of air improved conformity near air–tissue interfaces. Dental artifacts caused substantial target coverage overestimation even on MRIW + B + A. Geometrical distortion was less than 1 mm in an imaging volume 20 × 20 × 20 cm3 around scanner isocenter, but up to 4 mm at 17 cm lateral to isocenter. Bulk density assignment in the framework of MRI‐only IMRT head and neck treatment planning is a feasible method with certain limitations. Bone and teeth account for the majority of density heterogeneity effects. While soft tissue is well visualized on MRI compared to CT, dental implants may not be visible on MRI and must be identified by other means and assigned appropriate density for accurate dose calculation. Far off‐center geometrical distortion of the body contour near the shoulder region is a potential source of dose calculation inaccuracy. PACS numbers: 87.61. ‐c, 87.55. ‐D
Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage

Abstract Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self-crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5 to 16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press-fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage.
Synuclein‐γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study

Synuclein‐γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG‐8023).
Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study

Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system–penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers. Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were randomized to receive metformin then placebo for 8 weeks each or vice versa. CSF and neuroimaging (Arterial Spin Label MRI) data were collected for biomarker analyses, and cognitive testing was performed. Metformin was found to be safe, well-tolerated, and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention. No significant changes in cerebral blood flow were observed, though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure. Further study of these findings is warranted.
Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index

Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (<25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are composed of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2. The primary objective was to determine whether breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 kg/m2 (range, 18.4–24.9 kg/m2) in women with breast WAT inflammation versus 21.8 kg/m2 (range, 17.3–24.6 kg/m2) in those without inflammation (P = 0.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P < 0.05). Breast WAT inflammation correlated with larger adipocytes (P = 0.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P ≤ 0.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer. Cancer Prev Res; 10(4); 235–43. ©2017 AACR. See related article by Berger, p. 223–25.
CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

ABSTRACT African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of simian immunodeficiency virus (SIV) that do not progress to AIDS when infected with their species-specific viruses. Natural hosts of SIV express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo and that blocking of CCR5 does not prevent ex vivo infection of peripheral blood mononuclear cells (PBMC) from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro. Here we investigated the use of species-matched CXCR6 and other alternative coreceptors by SIVagmSab, which infects sabaeus AGM. We cloned sabaeus CD4 and 10 candidate coreceptors. Species-matched CXCR6, CCR5, and GPR15 mediated robust entry into transfected cells by pseudotypes carrying SIVagmSab92018ivTF Env, with lower-level entry through GPR1 and APJ. We cloned genetically divergent env genes from the plasma of two wild-infected sabaeus AGM and found similar patterns of coreceptor use. Titration experiments showed that CXCR6 and CCR5 were more efficient than other coreceptors when tested at limiting CD4/coreceptor levels. Finally, blocking of CXCR6 with its ligand CXCL16 significantly inhibited SIVagmSab replication in sabaeus PBMC and had a greater impact than did the CCR5 blocker maraviroc, confirming the use of CXCR6 in primary lymphocyte infection. These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4+ T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function. IMPORTANCE Natural hosts of SIV do not progress to AIDS, in stark contrast to pathogenic human immunodeficiency virus type 1 (HIV-1)-human and SIVmac-macaque infections. Identifying how natural hosts avoid immunodeficiency can elucidate key mechanisms of pathogenesis. It is known that despite high viral loads, natural hosts have a low frequency of CD4+ cells expressing the SIV coreceptor CCR5. In this study, we demonstrate the efficient use of the coreceptor CXCR6 by SIVagmSab to infect sabaeus African green monkey lymphocytes. In conjunction with studies of SIVsmm, which infects sooty mangabeys, and SIVagmVer, which infects vervet monkeys, our data suggest a unifying model whereby in natural hosts, in which the CCR5 expression level is low, the use of CXCR6 or other coreceptors to mediate infection may target SIV toward distinct cell populations that are able to support high-level viral replication without causing a loss of CD4+ T cell homeostasis and lymphoid tissue damage that lead to AIDS in HIV-1 and SIVmac infections.
Dosimetric impact of cylinder size in high‐dose rate vaginal cuff brachytherapy (VCBT) for primary endometrial cancer

The purpose of this study was to evaluate the dosimetric impact of cylinder size in high‐dose‐rate (HDR) vaginal cuff brachytherapy (VCBT). Sample plans of HDR VCBT in a list of cylinders ranging from 2.5 to 4 cm in diameter at 0.5 cm increment were created and analyzed. The doses were prescribed either at the 0.5 cm depth with 5.5 Gy for 4 fractions or at the cylinder surface with 8.8 Gy for 4 fractions, in various treatment lengths. A 0.5 cm shell volume called PTV_Eval was contoured for each plan and served as the target volume for dosimetric evaluation. The cumulative and differential dose volume histograms (c‐DVH and d‐DVH), mean doses (D‐mean) and the doses covering 90% (D90), 10% (D10), and 5% (D5) of PTV_Eval were calculated. In the 0.5 cm depth regimen, the DVH curves were found to have shifted toward the lower dose zone when a larger cylinder was used, but in the surface regimen the DVH curves shifted toward the higher dose zone as the cylinder size increased. The D‐means of the both regimens were between 6.9 and 7.8 Gy and dependent on the cylinder size but independent of the treatment length. A 0.5 cm variation of diameter could result in a 4% change of D‐mean. Average D90s were 5.7 (ranging from 5.6 to 5.8 Gy) and 6.1 Gy (from 5.7 to 6.4 Gy), respectively, for the 0.5 cm and surface regimens. Average D10 and D5 were 9.2 and 11 Gy, respectively, for the 0.5 cm depth regimen, and 8.9 and 9.7 Gy, respectively, for the surface regimen. D‐mean, D90, D10, and D5 for other prescription doses could be calculated from the lookup tables of this study. Results indicated that the cylinder size has moderate dosimetric impact, and that both regimens are comparable in dosimetric quality. PACS number(s): 87.61. ‐c, 87.53. Jw, 87.19. xj
Facets of Conscientiousness and risk of dementia

Background Multiple studies have found Conscientiousness to be protective against dementia. The purpose of this study is to identify which specific aspects, or facets, of Conscientiousness are most protective against cognitive impairment and whether these associations are moderated by demographic factors and/or genetic risk. Methods Health and Retirement Study participants were selected for analysis if they completed the facets of Conscientiousness measure, scored in the range of normal cognitive functioning at the baseline personality assessment, and had at least one follow-up assessment of cognition over the up to 6-year follow-up (N = 11 181). Cox regression was used to test for risk of incident dementia and risk of incident cognitive impairment not dementia (CIND). Results Over the follow-up, 278 participants developed dementia and 2186 participants developed CIND. The facet of responsibility had the strongest and most consistent association with dementia risk: every standard deviation increase in this facet was associated with a nearly 35% decreased risk of dementia; self-control and industriousness were also protective. Associations were generally similar when controlling for clinical, behavioral, and genetic risk factors. These three facets were also independent predictors of decreased risk of CIND. Conclusions The present research indicates that individuals who see themselves as responsible, able to control their behavior, and hard workers are less likely to develop CIND or dementia and that these associations persist after accounting for some common clinical, behavioral, and genetic risk factors.
Progress of flotation technology for high ash and fine mud content fine coal

China is the largest country in coal production and consumption in the world.Recently,with the increase of degrees of mechanization in coal mining,the particle size of raw coal more and more finer and with high ash content,which result in big problem for separating high ash content fine coal in coal preparation industry.According to the current situation of high ash content fine coal separation,the paper presents some typical flotation technologies for separating of high ash content fine coal,also points out the direction of high ash content fine coal separation.
Simulation as a teaching strategy for nursing education and orientation in cardiac surgery.

When exactly did you understand pulmonary artery (PA) catheters? Was it the first time you read about the mechanics of a PA catheter? Was it in the critical care course when the educator passed a catheter around and you could see all the ports? Was it when you saw a PA catheter inserted? Or was it the very first time you were the one responsible for putting a PA catheter together, assisting in the insertion, and then caring for the patient? Truly pinpointing exactly when you finally understood is probably difficult. Most likely it was a combination of these events that led to your full comprehension. The truth is, the understanding of something as complex as a PA catheter, or for that matter many aspects of critical care practice (eg, pacemakers, chest tubes, vasoactive drugs), does not happen in a single moment. This type of learning is cumulative, integrative, and multifaceted.
Trends in Secondary Schools’ Practices to Support Lesbian, Gay, Bisexual, Transgender, and Questioning Students, 2008-2014

Objectives To examine trends in the percentage of US secondary schools that implemented practices related to the support of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) students. Methods This analysis used data from 4 cycles (2008-2014) of School Health Profiles, a surveillance system that provides results representative of secondary schools in each state. Each school completed 2 self-administered questionnaires (principal and teacher) per cycle. We used logistic regression models to examine linear trends. Results Of 8 examined practices to support LGBTQ youths, only 1-identifying safe spaces for LGBTQ youths-increased in most states (72%) from 2010 to 2014. Among the remaining 7, only 1-prohibiting harassment based on a student’s perceived or actual sexual orientation or gender identity-had relatively high rates of adoption (a median of 90.3% of schools in 2014) across states. Conclusions Many states have seen no change in the implementation of school practices associated with LGBTQ students’ health and well-being.
Management of adrenocortical carcinoma

A 46-year-old woman presented with a 2-week history of a painless swelling in the left upper abdomen. Physical examination revealed a visible and palpable mass in the left upper abdominal quadrant. An abdominal ultrasound scan demonstrated a 14-cm well-defined mass, possibly left adrenal in origin. Plasma catecholamines, renin, aldosterone and cortisol were within normal ranges. Subsequent computed tomography (CT) imaging showed a well-defined, heterogenous 15.6 × 11.7 × 16.8 cm retroperitoneal mass, displacing the lower pole of the left kidney but not arising directly from it (Fig. 1). The left adrenal gland could not be identified separately. Following multidisciplinary team discussion, a laparotomy and left adrenalectomy was deemed the most appropriate management. The mass was excised completely intact and analyzed in the laboratory. The tumour dimensions were 160 × 120 × 143 mm with a weight of 1935 grams. There was a recognizable adrenal gland present at one edge of the specimen measuring 35 × 15 mm. The cut surface of the tumour had a nodular, solid and fleshy appearance with large areas of necrosis and haemorrhage present (Fig. 2). Histologically, the tumour was composed almost entirely of solid sheets of eosinophilic epithelial cells with foci of coagulative necrosis (Fig. 3). The nuclei were moderately pleomorphic with foci of marked pleomorphism. Mitotic activity was frequent (21 mitotic figures per 50 high-power fields) with occasional abnormal mitotic figures noted. The tumour was encapsulated and confined to the adrenal gland by the adrenal capsule. These findings were those of an oncocytic adrenocortical carcinoma, completely excised, with staging pT2 NX R0. Adrenal masses are among the most frequent tumours in humans, with the vast majority being benign. Adrenocortical carcinoma (ACC) is a rare, very aggressive malignancy affecting only 1–2 million people per year. ACC has a bimodal distribution, in which there is a relatively high incidence in children less than 5 years of age and in adults in their fourth and fifth decades of life. ACC often presents with symptoms of hormonal excess or a palpable mass. In approximately 60% of cases, the presentation of
Babesia microti: from Mice to Ticks to an Increasing Number of Highly Susceptible Humans

ABSTRACT Babesia microti, a zoonotic intraerythrocytic parasite, is the primary etiological agent of human babesiosis in the United States. Human infections range from subclinical illness to severe disease resulting in death, with symptoms being related to host immune status. Despite advances in our understanding and management of B. microti, the incidence of infection in the United States has increased. Therefore, research focused on eradicating disease and optimizing clinical management is essential. Here we review this remarkable organism, with emphasis on the clinical, diagnostic, and therapeutic aspects of human disease.
Common dietary patterns and risk of cancers of the colon and rectum: Analysis from the United Kingdom Women's Cohort Study (UKWCS)

Few prospective cohort studies in the UK have specifically focused on the associations between commonly consumed dietary patterns and colorectal cancer (CRC). The aim of our study was to assess whether red meat, poultry, fish and vegetarian dietary patterns are associated with differences in the incidence of cancers of colon and rectum in the UKWCS. Four common dietary patterns were defined based on a hierarchy of consumption of red meat, poultry and fish for each cohort participant, using a 217‐item food frequency questionnaire. Cox proportional hazards regression was used to provide adjusted hazard ratios (HR) and 95% confidence intervals (CI) for CRC. A total of 32,147 women recruited and surveyed between 1995 and 1998 were followed up for a mean of 17.2 years (426,798 person‐years). A total of 462 incident CRC cases were documented; 335 colon cancers (172 proximal and 119 distal) and 152 in the rectum. In multivariable‐adjusted models, there was no evidence of a reduction in risk of overall CRC (HR = 0.86, 95% CI: 0.66–1.12), colon cancer (HR = 0.77, 95% CI: 0.56–1.05) or rectal cancer (HR = 1.04, 95% CI: 0.66–1.63) when comparing grouped red meat free diets with diets containing red meat. Exploratory analysis suggested a reduced risk of distal colon cancer in grouped red meat free diets (HR = 0.56, 95% CI: 0.34–0.95), though numbers with this outcome were small. These results indicate that a protective association of red meat free diets specifically on distal colon cancer merits confirmation in a larger study.
Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.