83 research outputs found
HypBO: Expert-Guided Chemist-in-the-Loop Bayesian Search for New Materials
Robotics and automation offer massive accelerations for solving intractable,
multivariate scientific problems such as materials discovery, but the available
search spaces can be dauntingly large. Bayesian optimization (BO) has emerged
as a popular sample-efficient optimization engine, thriving in tasks where no
analytic form of the target function/property is known. Here we exploit expert
human knowledge in the form of hypotheses to direct Bayesian searches more
quickly to promising regions of chemical space. Previous methods have used
underlying distributions derived from existing experimental measurements, which
is unfeasible for new, unexplored scientific tasks. Also, such distributions
cannot capture intricate hypotheses. Our proposed method, which we call HypBO,
uses expert human hypotheses to generate an improved seed of samples.
Unpromising seeds are automatically discounted, while promising seeds are used
to augment the surrogate model data, thus achieving better-informed sampling.
This process continues in a global versus local search fashion, organized in a
bilevel optimization framework. We validate the performance of our method on a
range of synthetic functions and demonstrate its practical utility on a real
chemical design task where the use of expert hypotheses accelerates the search
performance significantly
Inverse Relationship between Adherence to the Mediterranean Diet and Serum Cystatin C Levels
OBJECTIVE: The aim of the present study was to examine serum cystatin C levels in association with the Mediterranean diet in a healthy Greek population. METHODS: Cystatin C together with basic clinical chemistry tests was measured in a total of 490 adults (46±16 years, 40% of males), who underwent an annual health check. Demographic, anthropometric and lifestyle characteristics were recorded, while adherence to the Mediterranean diet was evaluated through the MedDietScore (0-55). RESULTS: The mean level of serum cystatin C was 0.84 mg/L, while men had increased serum cystatin C levels compared to women (0.86 mg/L vs. 0.83 mg/L, respectively, 0.017). After adjusting for age, gender, body mass index, smoking status, hypertension, diabetes, hypercholesterolemia, estimated glomerular filtration rate (eGFR), albumin and ferritin levels, each unit increase in MedDietScore led to 0.002 mg/dL drop off in cystatin C serum levels. CONCLUSIONS: We have demonstrated an inverse relationship between the MedDietScore and serum cystatin C levels. Our finding that increases in MedDietScore are associated with decreases in serum cystatin C levels could imply that adherence to the Mediterranean diet may reduce the cardiovascular risk, as assessed by cystatin C, a prognostic marker of the cardiometabolic risk. This notion could have a great impact on public health
A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression
Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis
Homonymous hemianopsia as the leading symptom of a tumor like demyelinating lesion: a case report
Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?
OBJECTIVE
Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia.
METHODS
PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run.
RESULTS
97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness.
CONCLUSIONS
We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively
Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings
The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert® MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.PostprintPeer reviewe
Improving prehospital trauma management for skiers and snowboarders - need for on-slope triage?
Background
Injuries from skiing and snowboarding became a major challenge for emergency care providers in Switzerland. In the alpine setting, early assessment of injury and health status is essential for the initiation of adequate means of care and transport. Nevertheless, validated standardized protocols for on-slope triage are missing. This article can assist in understanding the characteristics of injured winter sportsmen and exigencies for future on-slope triage protocols.
Methods
Six-year review of trauma cases in a tertiary trauma centre. Consecutive inclusion of all injured skiers and snowboarders aged >15 (total sample) years with predefined, severe injury to the head, spine, chest, pelvis or abdomen (study sample) presenting at or being transferred to the study hospital. Descriptive analysis of age, gender and injury pattern.
Results
Amongst 729 subjects (total sample) injured from skiing or snowboarding, 401 (55%, 54% of skiers and 58% of snowboarders) suffered from isolated limb injury. Amongst the remaining 328 subjects (study sample), the majority (78%) presented with monotrauma. In the study sample, injury to the head (52%) and spine (43%) was more frequent than injury to the chest (21%), pelvis (8%), and abdomen (5%). The three most frequent injury combinations were head/spine (10% of study sample), head/thorax (9%), and spine/thorax (6%). Fisher's exact test demonstrated an association for injury combinations of head/thorax (p < 0.001), head/abdomen (p = 0.019), and thorax/abdomen (p < 0.001).
Conclusion
The data presented and the findings from previous investigations indicate the need for development of dedicated on-slope triage protocols. Future research must address the validity and practicality of diagnostic on-slope tests for rapid decision making by both professional and lay first responders. Thus, large-scale and detailed injury surveillance is the future research priority
Repurposing — a ray of hope in tackling extensively drug resistance in tuberculosis
Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections
StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation
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