Low-Cost Sensor Node for Air Quality Monitoring: Field Tests and Validation of Particulate Matter Measurements.

Air pollution is still a major public health issue, which makes monitoring air quality a necessity. Mobile, low-cost air quality measurement devices can potentially deliver more coherent data for a region or municipality than stationary measurement stations are capable of due to their improved spatial coverage. In this study, air quality measurements obtained during field tests of our low-cost air quality sensor node (sensor-box) are presented and compared to measurements from the regional air quality monitoring network. The sensor-box can acquire geo-tagged measurements of several important pollutants, as well as other environmental quantities such as light and sound. The field test consists of sensor-boxes mounted on utility vehicles operated by municipalities located in Central Switzerland. Validation is performed against a measurement station that is part of the air quality monitoring network of Central Switzerland. Often not discussed in similar studies, this study tests and discusses several data filtering methods for the removal of outliers and unfeasible values prior to further analysis. The results show a coherent measurement pattern during the field tests and good agreement to the reference station during the side-by-side validation test.

Fair-split distribution of multi-dose vaccines with prioritized age groups and dynamic demand: The case study of COVID-19.

The emergence of the SARS-CoV-2 virus and new viral variations with higher transmission and mortality rates have highlighted the urgency to accelerate vaccination to mitigate the morbidity and mortality of the COVID-19 pandemic. For this purpose, this paper formulates a new multi-vaccine, multi-depot location-inventory-routing problem for vaccine distribution. The proposed model addresses a wide variety of vaccination concerns: prioritizing age groups, fair distribution, multi-dose injection, dynamic demand, etc. To solve large-size instances of the model, we employ a Benders decomposition algorithm with a number of acceleration techniques. To monitor the dynamic demand of vaccines, we propose a new adjusted susceptible-infectious-recovered (SIR) epidemiological model, where infected individuals are tested and quarantined. The solution to the optimal control problem dynamically allocates the vaccine demand to reach the endemic equilibrium point. Finally, to illustrate the applicability and performance of the proposed model and solution approach, the paper reports extensive numerical experiments on a real case study of the vaccination campaign in France. The computational results show that the proposed Benders decomposition algorithm is 12 times faster, and its solutions are, on average, 16% better in terms of quality than the Gurobi solver under a limited CPU time. In terms of vaccination strategies, our results suggest that delaying the recommended time interval between doses of injection by a factor of 1.5 reduces the unmet demand up to 50%. Furthermore, we observed that the mortality is a convex function of fairness and an appropriate level of fairness should be adapted through the vaccination.

Production-sharing of critical resources with dynamic demand under pandemic situation: The COVID-19 pandemic.

The COVID-19 virus's high transmissibility has resulted in the virus's rapid spread throughout the world, which has brought several repercussions, ranging from a lack of sanitary and medical products to the collapse of medical systems. Hence, governments attempt to re-plan the production of medical products and reallocate limited health resources to combat the pandemic. This paper addresses a multi-period production-inventory-sharing problem (PISP) to overcome such a circumstance, considering two consumable and reusable products. We introduce a new formulation to decide on production, inventory, delivery, and sharing quantities. The sharing will depend on net supply balance, allowable demand overload, unmet demand, and the reuse cycle of reusable products. Undeniably, the dynamic demand for products during pandemic situations must be reflected effectively in addressing the multi-period PISP. A bespoke compartmental susceptible-exposed-infectious-hospitalized-recovered-susceptible (SEIHRS) epidemiological model with a control policy is proposed, which also accounts for the influence of people's behavioral response as a result of the knowledge of adequate precautions. An accelerated Benders decomposition-based algorithm with tailored valid inequalities is offered to solve the model. Finally, we consider a realistic case study - the COVID-19 pandemic in France - to examine the computational proficiency of the decomposition method. The computational results reveal that the proposed decomposition method coupled with effective valid inequalities can solve large-sized test problems in a reasonable computational time and 9.88 times faster than the commercial Gurobi solver. Moreover, the sharing mechanism reduces the total cost of the system and the unmet demand on the average up to 32.98% and 20.96%, respectively.

[18F]FDG PET radiomics to predict disease-free survival in cervical cancer: a multi-scanner/center study with external validation.

PURPOSE: To test the performances of native and tumour to liver ratio (TLR) radiomic features extracted from pre-treatment 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT and combined with machine learning (ML) for predicting cancer recurrence in patients with locally advanced cervical cancer (LACC). METHODS: One hundred fifty-eight patients with LACC from multiple centers were retrospectively included in the study. Tumours were segmented using the Fuzzy Local Adaptive Bayesian (FLAB) algorithm. Radiomic features were extracted from the tumours and from regions drawn over the normal liver. Cox proportional hazard model was used to test statistical significance of clinical and radiomic features. Fivefold cross validation was used to tune the number of features. Seven different feature selection methods and four classifiers were tested. The models with the selected features were trained using bootstrapping and tested in data from each scanner independently. Reproducibility of radiomics features, clinical data added value and effect of ComBat-based harmonisation were evaluated across scanners. RESULTS: After a median follow-up of 23 months, 29% of the patients recurred. No individual radiomic or clinical features were significantly associated with cancer recurrence. The best model was obtained using 10 TLR features combined with clinical information. The area under the curve (AUC), F1-score, precision and recall were respectively 0.78 (0.67-0.88), 0.49 (0.25-0.67), 0.42 (0.25-0.60) and 0.63 (0.20-0.80). ComBat did not improve the predictive performance of the best models. Both the TLR and the native models performance varied across scanners used in the test set. CONCLUSION: [18F]FDG PET radiomic features combined with ML add relevant information to the standard clinical parameters in terms of LACC patient's outcome but remain subject to variability across PET/CT devices.

Nipped-A regulates intestinal stem cell proliferation in Drosophila.

Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs. We show that Nipped-A is required for maintaining the proliferative capacity of ISCs during aging and in response to tissue-damaging or tumorigenic stimuli. Interestingly, Drosophila Myc cannot compensate for the effect of the loss of Nipped-A on ISC proliferation. Nipped-A seems to be a superordinate regulator of ISC proliferation, possibly by coordinating different processes including modifying the chromatin landscape of ISCs and progenitors.

Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist.

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+ -derived mesenchymal stem cells (MSCs) attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron-overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+ -derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+ -derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker-enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans. Stem Cells 2019;37:1057-1074.

Cellular circadian period length inversely correlates with HbA1c levels in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: The circadian system plays an essential role in regulating the timing of human metabolism. Indeed, circadian misalignment is strongly associated with high rates of metabolic disorders. The properties of the circadian oscillator can be measured in cells cultured in vitro and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed to discover whether molecular properties of the circadian oscillator are altered as a result of type 2 diabetes. METHODS: We assessed molecular clock properties in dermal fibroblasts established from skin biopsies taken from nine obese and eight non-obese individuals with type 2 diabetes and 11 non-diabetic control individuals. Following in vitro synchronisation, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. RESULTS: We observed a significant inverse correlation (ρ = -0.592; p < 0.05) between HbA1c values and circadian period length within cells from the type 2 diabetes group. RNA sequencing analysis conducted on samples from this group revealed that ICAM1, encoding the endothelial adhesion protein, was differentially expressed in fibroblasts from individuals with poorly controlled vs well-controlled type 2 diabetes and its levels correlated with cellular period length. Consistent with this circadian link, the ICAM1 gene also displayed rhythmic binding of the circadian locomotor output cycles kaput (CLOCK) protein that correlated with gene expression. CONCLUSIONS/INTERPRETATION: We provide for the first time a potential molecular link between glycaemic control in individuals with type 2 diabetes and circadian clock machinery. This paves the way for further mechanistic understanding of circadian oscillator changes upon type 2 diabetes development in humans. DATA AVAILABILITY: RNA sequencing data and clinical phenotypic data have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the European Bioinformatics Institute (EBI) and the Centre for Genomic Regulation (CRG), ega-box-1210, under accession no. EGAS00001003622.

Alpha-Ketoglutarate Curbs Differentiation and Induces Cell Death in Mesenchymal Stromal Precursors with Mitochondrial Dysfunction.

Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape. Our data identify impairment of the pyruvate and l-glutamine metabolism causing toxic accumulation of alpha-ketoglutarate in the Sod2-deficient and intrinsically aged stromal precursor cells as a major cause for their reduced lineage differentiation. Alpha-ketoglutarate accumulation led to enhanced nucleocytoplasmic vacuolation and chromatin condensation-mediated cell death in Sod2-deficient stromal precursor cells as a consequence of DNA damage, Hif-1α instability, and reduced histone H3 (Lys27) acetylation. These findings hold promise for prevention and treatment of mitochondrial disorders commonly associated with aged individuals. Stem Cells 2017;35:1704-1718.

A model of the onset of the senescence associated secretory phenotype after DNA damage induced senescence.

Cells and tissues are exposed to stress from numerous sources. Senescence is a protective mechanism that prevents malignant tissue changes and constitutes a fundamental mechanism of aging. It can be accompanied by a senescence associated secretory phenotype (SASP) that causes chronic inflammation. We present a Boolean network model-based gene regulatory network of the SASP, incorporating published gene interaction data. The simulation results describe current biological knowledge. The model predicts different in-silico knockouts that prevent key SASP-mediators, IL-6 and IL-8, from getting activated upon DNA damage. The NF-κB Essential Modulator (NEMO) was the most promising in-silico knockout candidate and we were able to show its importance in the inhibition of IL-6 and IL-8 following DNA-damage in murine dermal fibroblasts in-vitro. We strengthen the speculated regulator function of the NF-κB signaling pathway in the onset and maintenance of the SASP using in-silico and in-vitro approaches. We were able to mechanistically show, that DNA damage mediated SASP triggering of IL-6 and IL-8 is mainly relayed through NF-κB, giving access to possible therapy targets for SASP-accompanied diseases.

Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report.

BACKGROUND: The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism. CASE: A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy. CONCLUSION: The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation.

[Testosterone therapy in female hypoactive sexual desire disorder]. / Place de la testostérone dans le trouble du désir sexuel hypoactif chez la femme.

Hypoactive sexual desire disorder (HSDD) is a deficiency of sexual desire that causes marked personal or interpersonal distress. It occurs in approximately 1 in 10 adult women. A number of potential contributory factors (hormonal, neurobiological and psychosocial) have been identified. Testosterone plays an excitatory role in sexual desire but the mechanism is not yet well understood. Treatment with testosterone has been shown to improve sexual desire in menopausal women with HSDD. However, there are limited data concerning premenopausal women and long-term safety. At present, physiological testosterone preparations for use in women are not available in Switzerland.

NetBenchmark: a bioconductor package for reproducible benchmarks of gene regulatory network inference.

BACKGROUND: In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods. RESULTS: Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities. CONCLUSIONS: The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks.

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein-protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level.

Characterisation of seven newly established head and neck squamous cell carcinoma cell lines.

Seven squamous cell carcinoma cell lines were disintegrated from biopsies of patients with head and neck cancer. Genotyping tests verified the authenticity and the human origin of all seven lines. The cell lines designated as University of Kiel, Head and Neck (UKHN) -1 to -3 and UKHN-6 to -9 were subjected to flow cytometry and indirect immunofluorescence to assess aberrant DNA content. To confirm the squamous epithelial origin of the cells, the cytokeratin profile was immunocytologically analysed. The cell lines showed individual differences in mitotic frequency. UKHN-1, -6, -7 and -9 grew as monolayers, whereas UKHN-2, -3, and -8 tend to multilayer stratification. Overexpression of LOXL4 and Pim-1 proteins as distinctive features of head and neck carcinomas were shown in all seven cell lines. Inoculating SCID mice with these cell lines resulted in tumour formation, hence corroborating the tumourigenicity of all seven cell lines. The cell lines were also tested for high-risk HPV types using different DNA-based assays and found to be negative.

Regional Anesthesia in the Elite Athlete.

Elite athletes are exposed to an elevated risk of musculoskeletal injury which may present a significant threat to an athlete's livelihood. The perioperative anesthetic plan of care for these injuries in the general population often incorporates regional anesthesia procedures due to several benefits. However, some concern exists regarding the potential for regional anesthesia to adversely impact functional recovery in an elite athlete who may have a lower tolerance for this risk. This article aims to review the data behind this concern, discuss strategies to improve the safety of these procedures and explore the features of consent in this patient population.

No evidence of structural abnormality of the substantia nigra in adult attention-deficit/hyperactivity disorder: a pilot cross-sectional cohort study.

Background: Abnormal expansion of the echogenic substantia nigra (SN+) is a common observation in Parkinson's disease (PD) and considered a potential trait marker within this context. However, SN+ was also frequently detected in children diagnosed with attention-deficit/hyperactivity disorder (ADHD), where it has been discussed as a biomarker of maturational dopaminergic dysfunction. Interestingly, ADHD was recently linked to an elevated risk of PD in epidemiological studies, particularly among individuals treated with psychostimulants. Here, we investigated the potential of SN echogenicity as a disease biomarker in adults with ADHD and its relation to psychostimulant treatment. Methods: In an exploratory cross-sectional cohort study, we performed transcranial sonography of the SN in 30 adults (mean age 33.3 ± 7.6 years, 19 males/11 females) diagnosed with ADHD according to DSM-V criteria. Results and conclusions: In this pilot study, we observed no evidence of structural abnormalities of the SN among adults diagnosed with ADHD, thus questioning the potential of SN+ as a biomarker for ADHD in this population. Moreover, we found no evidence of treatment-related SN echogenicity changes that would link therapeutic psychostimulant use to alterations in the structural integrity of the SN.

Carbimazole-induced, ANCA-associated, crescentic glomerulonephritis: case report and literature review.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is a rare complication of antithyroid drug use that was first described with propylthiouracil. We describe an ANCA-associated rapidly progressive glomerulonephritis in a patient treated with carbimazole during 6 months for Graves disease that resulted in end-stage renal disease. A 66-year-old man treated with carbimazole for Graves disease was admitted for macroscopic hematuria and edema of the lower extremities. Laboratory work-up showed elevated serum creatinine (435 µmol/L), mixed hematuria, nephrotic range proteinuria, and a low positive c-ANCA titer with proteinase-3 specificity. Renal biopsy showed necrotizing, crescentic, pauci-immune glomerulonephritis. Carbimazole was discontinued and hemodialysis was initiated as well as high-dose glucocorticoids and pulses of intravenous cyclophosphamide. Despite immunosuppressive treatment, the patient remained dialysis-dependent at 6 months after diagnosis. Graves disease remained in remission after carbimazole withdrawal. ANCA-associated vasculitis manifesting as glomerulonephritis is a potential adverse effect of all antithyroid drugs. Although prognosis is usually good, end-stage renal disease may ensue in rare cases. Physicians should have a high index of suspicion in patients receiving antithyroid drugs who present with symptoms or signs suggestive of progressive renal disease.

Laparoscopic Repair of a Right-Sided Diaphragmatic Hernia: A Technical Report.

Introduction: Occult diaphragmatic hernias after trauma are relatively rare and may present months to years after the traumatic event. Clinical presentations range from asymptomatic incidental findings on imaging to life-threatening incarceration of abdominal visceral organs. This study presents a case of a patient with a symptomatic diaphragmatic hernia secondary to a trauma >30 years prior. A literature review of this defect was performed examining the pathophysiology, presentation, and operative considerations. Case Presentation: A 58-year-old male with a history of multiple traumatic motor vehicle accidents 30 years prior presented with abdominal pain and obstructive symptoms. Axial imaging demonstrated a right-sided diaphragmatic hernia defect containing small intestine, colon, and omentum. He ultimately underwent a transabdominal laparoscopic repair of the defect with mesh buttressing. Postoperative the patient recovered well and was discharged without complications. Conclusion: Limited data outside of case reports exist for surgical management of occult diaphragmatic hernias secondary to trauma. Reported management options include open and minimally invasive thoracic as well as open and minimally invasive abdominal approaches; each with advantages and disadvantages. Depending on the defect size, both primary repair and repair with mesh reinforcement are appropriate options. More data comparing the approach and repair technique are needed to determine the best technique.

STR-typing of ancient skeletal remains: which multiplex-PCR kit is the best?

AIM: To comparatively test nine co mmercially available short tandem repeat (STR)-multiplex kits (PowerPlex 16, 16HS, ES, ESI17, ESX17, S5 [all Promega]; AmpFiSTR Identifiler, NGM and SEfiler [all Applied Biosystems]) for their efficiency and applicability to analyze ancient and thus highly degraded DNA samples. METHODS: Fifteen human skeletal remains from the late medieval age were obtained and analyzed using the nine polymerase chain reaction assays with slightly modified protocols. Data were systematically compared to find the most meaningful and sensitive assay. RESULTS: The ESI, ESX, and NGM kits showed the best overall results regarding amplification success, detection rate, identification of heterozygous alleles, sex determination, and reproducibility of the obtained data. CONCLUSION: Since application of these three kits enables the employment of different primer sequences for all the investigated amplicons, a combined application is recommended for best possible and--most importantly--reliable genetic analysis of ancient skeletal material or otherwise highly degraded samples, e.g., from forensic cases.