Reliable Background Prediction Using Approximated GMM

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Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

[Purpose] A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. [Methods] We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. [Results] Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS-defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. [Conclusion] Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions

Bony fragment of apophyseal ring fracture

In this paper, we present 2 cases of herniated nucleus pulposus (HNP) combined with the residual bony fragment of apophyseal ring fracture. HNP typically exists at the narrow lateral recess formed by the bony fragment, and so it has been reported that symptoms may persist. Case 1 was a 22-year-old man, a high-level javelin thrower and Paralympic athlete. He had a history of persistent pain for 4 years due to HNP, and so we performed surgical removal. Case 2 was a 23-year-old male professional baseball player. He was referred to us only 17 days after the onset of pain and presented with muscle weakness, a feature which may prolong the clinical course in addition other features such as pain. Thus, we performed a comparatively quick intervention of surgical removal. In both cases, we had excellent clinical outcomes and better function and performance. In conclusion, in cases with HNP and apophyseal ring separation, surgical intervention in the comparatively early phase can be recommended, particularly if the patients desire quick return to their original level of activity

Comparison of testosterone fractions between Framingham Heart Study participants and Japanese participants

Objectives: To determine testosterone fractions in Japanese men and to compare these values with those of Framingham Heart Study participants. Methods: We enrolled 498 healthy Japanese men. Total testosterone was assayed by liquid chromatography tandem mass spectrometry, sex hormone-binding globulin was assayed by immunoassay and free testosterone was calculated by a laboratory at the Boston Medical Center. Analog-based free testosterone and immunoassay-based total testosterone were determined by immunoassay. We compared mass spectrometry assay-based total testosterone and calculated free testosterone values in the Japanese participants with values in the American Framingham Heart Study third generation cohort. Results: The mean serum mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone values were 439.4±167ng/dL, 65.34±30.61nmol/L, and 58.75±20.0pg/mL, respectively. The correlation coefficients with age for mass spectrometry assay-based total testosterone, sex hormone-binding globulin, and calculated free testosterone were 0.0010, 0.5041, and -0.496, respectively. There were no age-related changes in mass spectrometry assay-based total testosterone values in healthy men (P=0.981), whereas sex hormone-binding globulin and calculated free testosterone levels showed similar age-related changes (P<0.0001). Serum analog-based free testosterone levels (8.24±2.9pg/mL) showed age-related changes (P<0.0001) regardless of immunoassay-based total testosterone levels (P=0.828). Serum immunoassay-based total testosterone values (486.1±162.5ng/dL) correlated with serum mass spectrometry assay-based total testosterone values (r=0.740, 95% confidence interval 0.6965-0.7781, P<0.0001). Similarly, analog-based free testosterone and calculated free testosterone values showed a highly significant correlation (r=0.706, 95% confidence interval 0.6587-0.7473, P<0.0001). The analog-based free testosterone values were approximately 10% of the calculated free testosterone values. Conclusions: In contrast to the Framingham Heart Study cohort, total testosterone values in Japanese men are not associated with advancing age; thus, they cannot be used to diagnose late-onset hypogonadism in Japan. The analog-based free testosterone value can be considered instead as a suitable biochemical determinant for diagnosing late-onset hypogonadism syndrome. © 2014 The Japanese Urological Association

Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn’s disease

BACKGROUND: Crohn’s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. METHODS: Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as “hyper-flow” and “hypo-flow” according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson’s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). RESULTS: There were no significant differences in disease features or laboratory findings between “hypo-flow” lesions (n = 4) and “hyper-flow” lesions (n = 8). Histopathologically, “hyper-flow” lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did “hypo-flow” lesions. There was no apparent association between the blood flow and CDAI. CONCLUSIONS: In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions

Photometry and Polarimetry of 2010 XC15_{15}: Observational Confirmation of E-type Near-Earth Asteroid Pair

Asteroid systems such as binaries and pairs are indicative of physical properties and dynamical histories of the Small Solar System Bodies. Although numerous observational and theoretical studies have been carried out, the formation mechanism of asteroid pairs is still unclear, especially for near-Earth asteroid (NEA) pairs. We conducted a series of optical photometric and polarimetric observations of a small NEA 2010 XC$_{15}$ in 2022 December to investigate its surface properties. The rotation period of 2010 XC$_{15}$ is possibly a few to several dozen hours and color indices of 2010 XC$_{15}$ are derived as $g-r=0.435\pm0.008$, $r-i=0.158\pm0.017$, and $r-z=0.186\pm0.009$ in the Pan-STARRS system. The linear polarization degrees of 2010 XC$_{15}$ are a few percent at the phase angle range of 58$^{\circ}$ to 114$^{\circ}$. We found that 2010 XC$_{15}$ is a rare E-type NEA on the basis of its photometric and polarimetric properties. Taking the similarity of not only physical properties but also dynamical integrals and the rarity of E-type NEAs into account, we suppose that 2010 XC$_{15}$ and 1998 WT$_{24}$ are of common origin (i.e., asteroid pair). These two NEAs are the sixth NEA pair and first E-type NEA pair ever confirmed, possibly formed by rotational fission. We conjecture that the parent body of 2010 XC$_{15}$ and 1998 WT$_{24}$ was transported from the main-belt through the $\nu_6$ resonance or Hungaria region.Comment: Resubmitted to AAS Journals. Any comments are welcom

Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions

Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions

Study protocol for a multi-center, randomized controlled trial to develop Japanese denture adhesive guidelines for patients with complete dentures : the Denture Adhesive Guideline trial : study protocol for a randomized controlled trial

Background: Denture adhesives, characterized as medical products in 1935 by the American Dental Association, have been considered useful adjuncts for improving denture retention and stability. However, many dentists in Japan are hesitant to acknowledge denture adhesives in daily practice because of the stereotype that dentures should be inherently stable, without the aid of adhesives. The aim of this study is to verify the efficacy of denture adhesives to establish guidelines for Japanese users. The null hypothesis is that the application of denture adhesives, including the cream and powder types, or a control (isotonic sodium chloride solution) would not produce different outcomes nor would they differentially improve the set outcomes between baseline and day 4 post-application. Methods: This ten-center, randomized controlled trial with parallel groups is ongoing. Three hundred edentulous patients with complete dentures will be allocated to three groups (cream-type adhesive, powder-type adhesive, and control groups). The participants will wear their dentures with the denture adhesive for 4 days, including during eight meals (three breakfasts, two lunches, and three dinners). The baseline measurements and final measurements for the denture adhesives will be performed on the first day and after breakfast on the fourth day. The primary outcome is a general satisfaction rating for the denture. The secondary outcomes are denture satisfaction ratings for various denture functions, occlusal bite force, resistance to dislodgement, masticatory performance, perceived chewing ability, and oral health-related quality of life. Between-subjects comparisons among the three groups and within-subjects comparisons of the pre- and post-intervention measurements will be performed. Furthermore, a multiple regression analysis will be performed. The main analyses will be based on the intention-to-treat principle. A sample size of 100 subjects per group, including an assumed dropout rate of 10 %, will be required to achieve 80 % power with a 5 % alpha level. Discussion: This randomized clinical trial will provide information about denture adhesives to complete denture wearers, prosthodontic educators, and dentists in Japan. We believe this new evidence on denture adhesive use from Japan will aid dentists in their daily practice even in other countries