Modeling cancer metabolism on a genome scale

Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, this review discusses the challenges that genome‐scale modeling of cancer metabolism has been facing. We survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network‐level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, we outline a few new steps that may further advance this field

Vital Sign Monitoring Using FMCW Radar in Various Sleeping Scenarios

Remote monitoring of vital signs for studying sleep is a user-friendly alternative to monitoring with sensors attached to the skin. For instance, remote monitoring can allow unconstrained movement during sleep, whereas detectors requiring a physical contact may detach and interrupt the measurement and affect sleep itself. This study evaluates the performance of a cost-effective frequency modulated continuous wave (FMCW) radar in remote monitoring of heart rate and respiration in scenarios resembling a set of normal and abnormal physiological conditions during sleep. We evaluate the vital signs of ten subjects in different lying positions during various tasks. Specifically, we aim for a broad range of both heart and respiration rates to replicate various real-life scenarios and to test the robustness of the selected vital sign extraction methods consisting of fast Fourier transform based cepstral and autocorrelation analyses. As compared to the reference signals obtained using Embla titanium, a certified medical device, we achieved an overall relative mean absolute error of 3.6% (86% correlation) and 9.1% (91% correlation) for the heart rate and respiration rate, respectively. Our results promote radar-based clinical monitoring by showing that the proposed radar technology and signal processing methods accurately capture even such alarming vital signs as minimal respiration. Furthermore, we show that common parameters for heart rate variability can also be accurately extracted from the radar signal, enabling further sleep analyses.publishedVersionPeer reviewe

Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.Peer reviewe

Pink verrucous plaque in a man with systemic mastocytosis

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common

Femoral avulsion of the medial patellofemoral ligament after primary traumatic patellar dislocation predicts subsequent instability in men : a mean 7-year nonoperative follow-up study

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Eosinophilic fasciitis presenting as a unilateral, solitary plaque

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis

Internal structure and physical properties of the Asteroid 2008 TC3 inferred from a study of the Almahata Sitta meteorites

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Educational achievement of children with selected major congenital anomalies and associated factors: a Finnish registry-based study

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association. BACKGROUND: Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors. METHODS: We performed a registry-based study including 401 544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and \u27All anomalies\u27 subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children. RESULTS: Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92-4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the \u27All anomalies\u27 subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement. CONCLUSIONS: For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background

Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

One Screening Magnetic Resonance Imaging Sequence in Evaluation of Chondral and Meniscal Lesions of the Knee − A Pilot Study

This prospective study aimed to evaluate if chondral and meniscal lesions in symptomatic knees of osteoarthritis patients can be reliably identified using only one sagittal dual-echo MRI (Magnetic Resonance Imaging) sequence. MRI was performed on 13 patients after knee arthroscopy due to knee pain and clinically suspected osteoarthritis using a 1.5-Tesla scanner with knee coil and a sagittal dual-echo turbo spin-echo PD (Proton Density)- and T2-weighted sequence. The MRI and arthroscopic findings were then compared. Of 65 articular surfaces, 47 were damaged. For articular cartilage lesions, the overall sensitivity of MRI was 46.8%, specificity 72.2%, and diagnostic accuracy 53.9%, and for meniscal ruptures 81.2%, 66.7%, and 73.1%, respectively. The present study showed that the reliability of screening MRI of knees using only one sagittal dual-echo sequence does not suffice for diagnosis of chondral or meniscal lesions, and should therefore not replace routine knee MRI or diagnostic arthroscopy