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Score-driven models have recently been introduced as a general framework to specify time-varying parameters of conditional densities. The score enjoys stochastic properties that make these models easy to implement and convenient to apply in several contexts, ranging from biostatistics to finance. Score-driven parameter updates have been shown to be optimal in terms of locally reducing a local version of the Kullback–Leibler divergence between the true conditional density and the postulated density of the model. A key limitation of such an optimality property is that it holds only locally both in the parameter space and sample space, yielding to a definition of local Kullback–Leibler divergence that is in fact not a divergence measure. The current paper shows that score-driven updates satisfy stronger optimality properties that are based on a global definition of Kullback–Leibler divergence. In particular, it is shown that score-driven updates reduce the distance between the expected updated parameter and the pseudo-true parameter. Furthermore, depending on the conditional density and the scaling of the score, the optimality result can hold globally over the parameter space, which can be viewed as a generalization of the monotonicity property of the stochastic gradient descent scheme. Several examples illustrate how the results derived in the paper apply to specific models under different easy-to-check assumptions, and provide a formal method to select the link function and the scaling of the score. [ABSTRACT FROM AUTHOR]

Introduction Nowadays, in Europe, an enormously rich variety of foods is available on the market, and this very abundance, especially of energy-dense foods and drinks, is considered to be one [...], Objectives: To describe energy intake and its macronutrient and food sources among 27 regions in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36034 subjects aged 35-74 years were administered a standardized 24-h dietary recall. Intakes of macronutrients (g/day) and energy (kcal/day) were estimated using standardized national nutrient databases. Mean intakes were weighted by season and day of the week and were adjusted for age, height and weight, after stratification by gender. Extreme low- and high-energy reporters were identified using Goldberg's cutoff points (ratio of energy intake and estimated basal metabolic rate 2.72), and their effects on macronutrient and energy intakes were studied. Results: Low-energy reporting was more prevalent in women than in men. The exclusion of extreme-energy reporters substantially lowered the EPIC-wide range in mean energy intake from 2196-2877 to 2309-2866 kcal among men. For women, these ranges were 1659-2070 and 1873-2108 kcal. There was no north-south gradient in energy intake or in the prevalence of low-energy reporting. In most centres, cereals and cereal products were the largest contributors to energy intake. The food groups meat, dairy products and fats and oils were also important energy sources. In many centres, the highest mean energy intakes were observed on Saturdays. Conclusions: These data highlight and quantify the variations and similarities in energy intake and sources of energy intake among 10 European countries. The prevalence of low-energy reporting indicates that the study of energy intake is hampered by the problem of underreporting. Keywords: energy intake; underreporting; dietary fat; 24-h dietary recall; Europe; EPIC-soft doi: 10.1038/ejcn.2009.72

Abstract Inherited bone disorders account for about 10% of documented Mendelian disorders and are associated with high financial burden. Their study requires osteoblasts which play a critical role in regulating the development and maintenance of bone tissue. However, bone tissue is not always available from patients. We developed a highly efficient platelet lysate-based approach to directly transdifferentiate skin-derived human fibroblasts to osteoblast-like cells. We extensively characterized our in vitro model by examining the expression of osteoblast-specific markers during the transdifferentiation process both at the mRNA and protein level. The transdifferentiated osteoblast-like cells showed significantly increased expression of a panel of osteogenic markers. Mineral deposition and ALP activity were also shown, confirming their osteogenic properties. RNA-seq analysis allowed the global study of changes in the transcriptome of the transdifferentiated cells. The transdifferentiated cells clustered separately from the primary fibroblasts with regard to the significantly upregulated genes indicating a distinct transcriptome profile; transdifferentiated osteoblasts also showed significant enrichment in gene expression related to skeletal development and bone mineralization. Our presented in vitro model may potentially contribute to the prospect of studying osteoblast-dependent disorders in patient-derived cells.

IntroductionOsteogenesis Imperfecta is a rare genetic connective tissue disorder, characterized by skeletal dysplasia and fragile bones. Currently only two mouse models have been reported for haploinsufficient (HI) mild Osteogenesis Imperfecta (OI); the Col1a1+/Mov13 (Mov13) and the Col1a1+/-365 mouse model. The Mov13 mice were created by random insertion of the Mouse Moloney leukemia virus in the first intron of the Col1a1 gene, preventing the initiation of transcription. Since the development of the Mov13 mice almost four decades ago and its basic phenotypic characterization in the 90s, there have not been many further studies. We aimed to extensively characterize the Mov13 mouse model in order to critically evaluate its possible use for preclinical studies of HI OI.MethodsBone tissue from ten heterozygous Mov13 and ten wild-type littermates (WT) C57BL/6J mice (50% males per group) was analyzed at eight weeks of age with bone histomorphometry, micro computed tomography (microCT), 3-point bending, gene expression of different collagens, as well as serum markers of bone turnoverResultsThe Mov13 mouse presented a lower bone strength and impaired material properties based on our results of 3-point bending and microCT analysis respectively. In contrast, no significant differences were found for all histomorphometric parameters. In addition, no significant differences in Col1a1 bone expression were present, but there was a significant lower P1NP concentration, a bone formation marker, measured in serum. Furthermore, bone tissue of Mov13 mice presented significantly higher expression of collagens (Col1a2, Col5a1 and Col5a2), and bone metabolism markers (Bglap, Fgf23, Smad7, Edn1 and Eln) compared to WT. Finally, we measured a significantly lower Col1a1 expression in heart and skin tissue and also determined a higher expression of other collagens in the heart tissue.ConclusionAlthough we did not detect a significant reduction in Col1a1 expression in the bone tissue, a change in bone structure and reduction in bone strength was noted. Regrettably, the variability of the bone phenotype and the appearance of severe lymphoma in adult Mov13 mice, does not favor their use for the testing of new long-term drug studies. As such, a new HI OI type 1 mouse model is urgently needed.

Humanitarian engineers responded to the pandemic ventilator shortage of March, 2020 by beginning over 100 open source ventilator projects [Robert L. Read et al. COVID-19 Vent List. Oct. 2020. url: https://docs.google.com/spreadsheets/d/1inYw5H4RiL0AC_J9vPWzJxXCdlkMLPBRdPgEVKF8DZw/edit#gid=0, Joshua M. Pearce. A review of open source ventilators for COVID-19 and future pandemics. In: F1000Research 9 (2020).]. By ventilator, we mean both an invasive ventilator (requiring intubation of the patient) and non-invasive ventilator (generally supporting spontaneously breathing). Inexpensive ventilator test equipment can facilitate projects forced to be geographically distributed by lockdowns. The VentMon is a modular, open source, IoT-enabled tester that plugs into a standard 22 mm airway between a ventilator and a physical test lung to test any ventilator. The VentMon measures flow, pressure, fractional oxygen, humidity, and temperature. Data is stored and graphed at a data lake accessible to all devlopment team members, and, eventually, clinicians. The open source design of the VentMon, its firmware, and cloud-based software may allow it to be used as a component of modular ventilators to provide a clinical readout. The software system surrounding VentMon has been designed to be as modular and composable as possible. By combining new, openly published standards for data with composable and modifiable hardware, the VentMon forms the beginning of an open system or eco-system of ventilation devices and data. Thanks to grants, 20 VentMons have been given away free of charge to pandemic response teams building open source ventilators.

Bone tissue degeneration is an urgent clinical issue, making it a subject of intensive research. Chronic skeletal disease forms can be prevalent, such as the age-related osteoporosis, or rare, in the form of monogenetic bone disorders. A barrier in the understanding of the underlying pathological process is the lack of accessibility to relevant material. For this reason, cells of non-bone tissue are emerging as a suitable alternative for models of bone biology. Fibroblasts are highly suitable for this application; they populate accessible anatomical locations, such as the skin tissue. Reports suggesting their utility in preclinical models for the study of skeletal diseases are increasingly becoming available. The majority of these are based on the generation of an intermediate stem cell type, the induced pluripotent stem cells, which are subsequently directed to the osteogenic cell lineage. This intermediate stage is circumvented in transdifferentiation, the process regulating the direct conversion of fibroblasts to osteogenic cells, which is currently not well-explored. With this mini review, we aimed to give an overview of existing osteogenic transdifferentiation models and to inform about their applications in bone biology models.

This study aims to assess type of melanin as a risk indicator for skin tumors, in a sample of melanoma cases and controls within a larger multicenter study (Helios 2), held in Europe and South America in 2001-2002. In each case and control, the melanin content in hair was assessed by three methods: 1) the amount of 2,3,5-pyrroletricarboxylic acid (PTCA); 2) the absorbance ratio with ultraviolet spectroscopy; and 3) the spectra of near-infrared spectroscopy. Statistical analysis was performed in a Bayesian setting, defining priors for confounders and effect modifiers from the larger study data set. Subjects with values of PTCA of less than 85 ng/mg carried an increased risk (26 vs. seven discordant pairs: odds ratio = 4.4, 95% confidence interval: 1.52, 14.54), adjusted by hair color, eye color, and number of nevi (n = >/=40). The absorbance ratio showed a weaker and nonsignificant odds ratio of 1.5. After correction by misclassification, near-infrared spectroscopy was associated with an odds ratio of 2.3 (95% confidence interval: 1.36, 4.22). The amount of PTCA is thus a strong and independent risk indicator for melanoma. Incorporating PTCA determination into epidemiologic studies is therefore recommended. [ABSTRACT FROM AUTHOR]

Background. Kaposi sarcoma (KS) is primarily caused by human herpesvirus (HHV)-8 infection, and the risk is increased with high HHV-8 lytic or latent antibody titers or the detection of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). Host genes important for control of HHV-8 infection are not well characterized.Methods. In 172 HHV-8 latent nuclear antigen (LANA)-seropositive adults in Italy without KS, we examined correlations of common variants in host immune genes with the detection of HHV-8 DNA in PBMCs and with high lytic and latent antibody titers. Twenty-eight single-nucleotide polymorphisms in 14 genes were analyzed. We detected HHV-8 DNA in PBMCs with real-time amplification of the K6 gene, anti-K8.1 (lytic) titers with enzyme-linked immunosorbent assay, and anti-LANA (latent) titers with immunofluorescence.Results. Detection of HHV-8 DNA in PBMCs was not significantly related to any variant examined. In contrast, a 3-locus haplotype of IL4, which contains the -1098G allele (rs2243248), was overrepresented among subjects with high lytic titers (odds ratio [OR], 2.8 [95% confidence interval {CI}, 1.1-6.7]), compared with those with low titers, as was the functional promoter variant of IL6, C-236C (rs1800795) (OR, 3.7 [95% CI, 1.1-12.8]). Compared with subjects with low HHV-8 latent antibody titers, analysis of inferred haplotypes for IL12A revealed an overrepresentation of -798T/277A in subjects with high HHV-8 latent antibody titers (OR, 2.4 [95% CI, 1.1-5.2]).Conclusions. Our observations are the first to provide preliminary evidence suggesting that common variants in key host immune genes could influence the control of HHV-8 infection. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Focuses on a study which tested whether the recovered ability of rats to discriminate sodium chloride from potassium chloride after chorda tympani nerve transection is linked to nerve regeneration. Methodology of the study; Results and discussion; Conclusion.

Abstract Background Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS). Methods In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with Ptrend ≤ 0.15 were retained in a backward elimination regression model. Results Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (ORadj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, Ptrend = 0.87], nor was it related to any factor scores or cluster of plants (P = 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (Ptrend = 0.02 to 0.10) and with residential exposure to six soils (Ptrend = 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (ORadj 4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (ORadj 7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (ORadj 0.26 and 0.47, respectively, Ptrend = 0.05). Conclusions KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.

Abstract Background To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV). Methods In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods. Results Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07) and anti-VCA (P = 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03), and they were marginally lower with older age and cortisone use (Padj ≤ 0.09). Conclusions Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.

Piñon-juniper (PJ) woodlands are a dominant community type across the Intermountain West, comprising over a million acres and experiencing critical effects from increasing wildfire. Large PJ mortality and regeneration failure after catastrophic wildfire have elevated concerns about the long-term viability of PJ woodlands. Thinning is increasingly used to safeguard forests from fire and in an attempt to increase climate resilience. We have only a limited understanding of how fire and thinning will affect the structure and function of PJ ecosystems. Here, we examined vegetation structure, microclimate conditions, and PJ regeneration dynamics following ~20 years post-fire and thinning treatments. We found that burned areas had undergone a state shift that did not show signs of returning to their previous state. This shift was characterized by (1) distinct plant community composition dominated by grasses; (2) a lack of PJ recruitment; (3) a decrease in the sizes of interspaces in between plants; (4) lower abundance of late successional biological soil crusts; (5) lower mean and minimum daily soil moisture values; (6) lower minimum daily vapor pressure deficit; and (7) higher photosynthetically active radiation. Thinning created distinct plant communities and served as an intermediate between intact and burned communities. More intensive thinning decreased PJ recruitment and late successional biocrust cover. Our results indicate that fire has the potential to create drier and more stressful microsite conditions, and that, in the absence of active management following fire, there may be shifts to persistent ecological states dominated by grasses. Additionally, more intensive thinning had a larger impact on community structure and recruitment than less intensive thinning, suggesting that careful consideration of goals could help avoid unintended consequences. While our results indicate the vulnerability of PJ ecosystems to fire, they also highlight management actions that could be adapted to create conditions that promote PJ re-establishment., (© 2024 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Migraine is a neurological disease with a high incidence. The new anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have demonstrated effectiveness in preventing episodic and chronic migraine., Objective: To collect evidence of the real-world effectiveness of anti-CGRP mAbs by assessing outcomes such as reduction in monthly migraine days (MMDs), reduction in monthly headache days (MHDs), and percentage of patients having a 50% reduction in MMDs., Data Sources: The PubMed database was searched for the period from inception to October 20, 2021., Study Selection and Data Extraction: Of interest for this review were studies that evaluated the real-world effectiveness of anti-CGRP mAbs in terms of MMDs and reduction in MHDs. The search terms included "migraine", "monthly migraine days", and various drug names. The data are reported in terms of patients' baseline characteristics and treatment effectiveness., Data Synthesis: A total of 46 studies were evaluated, of which 30 (enrolling a total of 4273 patients across 10 countries) were included in the systematic review. The greatest absolute reduction in MMD was from 20.4 at baseline to 10.7 after 3 months of treatment. After 6 months, the greatest absolute difference was 10, relative to baseline. The largest absolute reduction in MHD at 3 months was from 22 to 8, whereas at 6 months, the greatest absolute reduction in MHD was 13. The treatment could be considered clinically effective (≥ 50% reduction in MMDs) for 41% of patients at 3 months and about 44% of patients at 6 months., Conclusions: Despite substantial variability in baseline values, this review confirmed the effectiveness of anti-CGRP mAbs, which yielded important clinical reductions in both MMDs and MHDs., Competing Interests: Competing interests: Andrea Zovi received a grant from Chiesi to attend a national congress. No other competing interests were declared. z, (2024 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Background: The development of alcoholic cardiomyopathy (ACM) is related to chronic excessive alcohol use. However, features of early-stage ACM are still unclear. We assessed echocardiographic characteristics of patients with alcohol dependence (DSM-IV criteria) during a six-month treatment period., Methods: Active drinking patients, heavy alcohol users, without heart disease, referred to our Alcohol Addiction Unit were enrolled in the study. After signing informed consent, patients started outpatient treatment program. Echocardiography was performed at enrollment, then three and six months afterwards, by cardiologists blinded to drinking status., Results: Forty-three patients (36 males, 7 females) were enrolled. At six months, 20 patients (46.5%) reduced alcohol consumption below heavy drinking levels. Although within normal range, baseline mean IVS thickness and mean LVDD were significantly higher (p < 0.001) and mean EF significantly reduced (p = 0.009), as compared to age-matched mean references. Mean E/A ratio, DcT and LA diameter were significantly different (p < 0.001) from mean references, but within normal range. Baseline mean E/e' ratio was significantly higher than the mean reference (p < 0.001) and out of the normal range. A significant correlation between the number of drinks per drinking days in the 7 days before baseline assessment and E/e' ratio was observed (p = 0.028). After six months, a trend-level reduction of mean E/e' ratio (p = 0.051) was found in the whole sample; this reduction was statistically significant (p = 0.041) among patients reducing drinking, compared to baseline., Conclusions: Altered E/e' ratio may characterize early-ACM before the occurrence of relevant echocardiographic alterations. The reduction of alcohol consumption could restore this alteration after six months., (Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)