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BackgroundGrowing evidence points to a link between specific fatty acids ingested through the diet and human health. Chain length, saturation degree, and position of double bonds in fatty acids determine their effect in humans. Omega-3 and omega-6 fatty acids have been recognized for their contribution to the prevention and/or treatment of diabetes, cancer, visual impairment, cardiovascular diseases, as well as neurological and musculoskeletal disorders. Scope and approachHumans cannot synthesize these fatty acids in sufficient amounts and need to absorb them through the diet. Oleaginous microalgae constitute a promising, sustainable source of such fatty acids, as they can accumulate up to 85% of lipids on a cell dry weight basis. Key findings and conclusionsThe present review summarizes the potential of oleaginous microalgae as a convenient, economical, and sustainable source of polyunsaturated fatty acids, and explores their beneficial role in human health. The growing prevalence of cardiovascular diseases and changing dietary preferences are driving the increasing demand for microbial omega-3 fatty acids. Following the COVID-19 pandemic, the importance of a healthy immune system has further strengthened the market for omega-3 fatty acids. Validerad;2023;Nivå 2;2023-05-12 (hanlid);Funder: Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT) (1137) Green and sustainable approach to valorise high saline and oily fish processing effluents for production of nutraceuticals Boosting the squalene content in thraustochytrids by genetic engineering using CRISPR–Cas9 System to replace shark-based squalene as an adjuvant for COVID 2019 vaccine

Any insult to the central nervous system can lead to the rare occurrence of neurogenic pulmonary oedema (NPO). It is usually associated with significant neurological injury (eg, subarachnoid haemorrhage or traumatic brain injury) with a relatively rapid onset. As an exception to this observation, we report a middle-aged woman who developed NPO 72 hours after the onset of a subtle but evolving right middle cerebral artery infarction confirmed on CT. Aggressive use of diuretics and vasodilators, as is normally the case for cardiogenic pulmonary oedema, can compromise cerebral blood flow and the ischaemic penumbra. This case illustrates how the diagnostic and therapeutic challenges were successfully addressed with the aid of bedside ultrasonography and close haemodynamic monitoring to reverse the respiratory failure while protecting the brain.

Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN. Significance: Our findings raise the potential for clinical development of drugs targeting CHAF1B to enhance IFN antitumor responses in the treatment of patients with MPN and should have important clinical translational implications for the treatment of MPN and possibly in other malignancies.

The speed and accuracy of the distribution of goods is an important factor that is continuously driven by shipping service companies. Service quality has a very important impact on determining the quality of the company. Pos Indonesia has a next day (H+1) goods delivery service product under the name Pos Express. However, in cases that occur in the field, Pos Express has problems in shipping goods in the form of delays in delivery. These problems have an impact on the quality of services provided by Pos Indonesia to its consumers. The purpose of this study is to analyze the causes of delays in delivery of goods and provide recommendations for improvements to Pos Express products. The method used in this research is Six Sigma with the DMAIC approach. The results of this study are delivery delays that are influenced by human error factors (counter clerk errors, inexperienced couriers, and sorting officer errors) which can be overcome by providing guidance and imposing sanctions on related workers, less prime vehicle conditions which can be overcome by periodic checking just before leaving, transportation planning errors that can be overcome through re-planning by considering the vehicle's load capacity and the number of goods on hand, and traffic jams that can be overcome by determining delivery routes and delivery times that are far from heavy traffic flows., Kecepatan dan ketepatan pendistribusian barang menjadi faktor penting yang terus dipacu oleh perusahaan jasa pengiriman. Kualitas pelayanan memiliki dampak yang sangat penting pada penentuan kualitas perusahaan. Pos Indonesia memiliki produk layanan pengiriman barang next day (H+1) dengan nama Pos Express. Namun dalam kasus yang terjadi di lapangan, Pos Express memiliki masalah dalam pengiriman barang berupa keterlambatan pengiriman. Permasalahan tersebut berakibat pada kualitas layanan yang diberikan Pos Indonesia kepada konsumennya. Tujuan dari penelitian ini adalah menganalisis penyebab terjadinya keterlambatan pengiriman barang dan memberikan rekomendasi perbaikan pada produk Pos Express. Metode yang digunakan dalam penelitian adalah Six Sigma dengan pendekatan DMAIC. Hasil dari penelitian ini adalah keterlambatan pengiriman yang dipengaruhi oleh faktor human error (kesalahan petugas loket, kurir kurang berpengalaman, dan kesalahan petugas sortir) yang dapat diatasi dengan melakukan pembinaan serta pemberian sanksi pada pekerja terkait, kondisi kendaraan kurang prima yang dapat diatasi dengan pengecekan berkala sesaat sebelum berangkat, kesalahan perencanaan transportasi yang dapat diatasi melalui perencanaan ulang dengan mempertimbangkan kapasitas muat kendaraan dan jumlah barang yang ada, dan kemacetan lalu lintas yang dapat diatasi dengan penetapan rute pengiriman serta waktu pengiriman yang jauh dari arus padat lalu lintas.

Objectives: Accurate prediction of stock market returns is a very challenging task due to the volatile and non-linear nature of the financial stock markets. In this work, we consider conventional time series analysis techniques with additional information from the Google Trend website to predict stock price returns. We further utilize a machine learning algorithm, namely Random Forest, to predict the next day closing price of four Greek systemic banks. Methods/Analysis: The financial data considered in this work comprise Open, Close prices of stocks and Trading Volume. In the context of our analysis, these data are further used to create new variables that serve as additional inputs to the proposed machine learning based model. Specifically, we consider variables for each of the banks in the dataset, such as 7 DAYS MA,14 DAYS MA, 21 DAYS MA, 7 DAYS STD DEV and Volume. One step ahead out of sample prediction following the rolling window approach has been applied. Performance evaluation of the proposed model has been done using standard strategic indicators: RMSE and MAPE. Findings: Our results depict that the proposed models effectively predict the stock market prices, providing insight about the applicability of the proposed methodology scheme to various stock market price predictions. Novelty /Improvement: The originality of this study is that Machine Learning Methods highlighted by the Random Forest Technique were used to forecast the closing price of each stock in the Banking Sector for the following trading session. Doi: 10.28991/ESJ-2023-07-03-04 Full Text: PDF

Esta investigación tiene como finalidad adaptar las diferentes inteligencias múltiples asociadas al contexto administrativo del desempeño docente. El objetivo general es diagnosticar los diferentes niveles de inseguridad económica y social que inciden en el desarrollo de las competencias de los bachilleres analizando la acción – reacción del análisis psicosocial para gestionar correctamente la aplicación de una didáctica adaptada al contexto de sus inteligencias múltiples. La metodología empleada, es un estudio de campo, en el que se elige un tamaño de la muestra de 70 estudiantes del primer y séptimo semestre de la carrera de Licenciatura en Educación de la Universidad Estatal de Milagro. Se descubre la relación existente entre la deserción universitaria y el contexto de la gestión sin el desarrollo de inteligencias múltiples directivas, lo que perjudica a los estudiantes en su seguridad y bienestar para el rendimiento académico. Se concluye que en la medida que las autoridades y docentes desarrollen sus inteligencias de gestión disminuye la vulnerabilidad y la deserción universitaria.

Software watermarking is a defense technique used to prevent or discourage software piracy by embedding a signature in the code. In (Discrete Applied Mathematics 250 (2018) 145–164), a software watermarking system is presented which encodes an integer number w (i.e., a watermark) as a reducible permutation flow-graph F [ π ∗ ] embeddable in the code through the use of a self-inverting permutation π ∗ . In this work, we theoretically investigate this watermarking system and exploit structural properties of the self-inverting permutation π ∗ encoding the watermark in order to prove its resilience to edge-modification attacks on the flow-graph F [ π ∗ ]. Based on the minimum number of edge modifications needed to be applied on F [ π ∗ ] so that a different watermark can be extracted from the resulting graph, we give a characterization of the watermarks as strong, intermediate or weak and provide good recommendations for the choices of watermark.

To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy.In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation.We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2).A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

We determined the scope of five decision models of choices across four environmental niches defined by whether outcome probabilities are described (risk) or experienced by sampling (uncertainty) and whether lotteries are simple (one or two outcomes per prospect) or complex (three or four). The majority of participants chose in accordance with cumulative prospect theory only in simple environments involving decisions from description (75%). In complex environments involving decisions from description and experience, however, skewness-preference models were more prevalent (57% and 68%, respectively). Consequently, in niches outside of simple lotteries under risk, rank dependence and nonlinear probability weighting failed to accurately describe the majority of choices. Exploiting elicited subjective beliefs in decisions from experience, we found that experienced (sampled) outcome likelihoods outperformed elicited beliefs in predicting choices and found scant evidence for two-stage models of decisions under uncertainty. Finally, we found statistically significant evidence that 90% of participants chose as if they relied on different models across environments; nonetheless, assuming as if participants used a single model across all environments to predict out-of-sample choice only minimally reduced prediction accuracy. We discuss the implications of model mimicry and task diagnosticity in light of these results in terms of both economic and statistical significance, both for model comparisons and inference. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Apesar das vantagens do Green Supply Chain Management (GSCM), existem barreiras que impedem a adoção das suas práticas pelas empresas. O presente artigo visa, por meio de uma Revisão Bibliográfica Sistemática (RBS) e dois estudos de caso, compreender melhor as práticas do GSCM e reconhecer as principais barreiras impostas a duas empresas (fabricante-fornecedor) do setor eletroeletrônico. Foram identificadas na literatura 25 práticas e 72 barreiras à implementação da GSCM. A partir dos estudos de caso, infere-se que a empresa foco A esteja mais desenvolvida em termos de GSCM e sustentabilidade ambiental do que seu fornecedor avaliado, devido à maior implementação de práticas do GSCM. Quanto às práticas, na Empresa A, a maior parte das práticas está totalmente implementada (19 delas), sendo 6 parcialmente implementadas e nenhuma não está implementada; e no Fornecedor, a maior parte está parcialmente implementada, somente 1 está totalmente implementada e 7 não estão implementadas. O entrevistado do fornecedor não soube opinar sobre várias práticas e barreiras. Quanto às categorias de barreiras, a empresa A enfrenta mais as barreiras de ‘stakeholders’ (12 barreiras), enquanto que o Fornecedor enfrenta mais barreiras de ‘conhecimento’ (8) e de ‘gestão’ (6).

In a world where the volume of data is constantly increasing, the implementation time of various processes increases significantly. Therefore, the proper management and the effort to reduce the dimensions of the datasets are considered imperative. Feature selection can reduce the size of the datasets by keeping a smaller subset, while improving the accuracy of the classification. The main purpose of this paper is to propose and examine the efficiency of parallel feature selection wrappers based on k-means classifier. The simple kmeans algorithm and a parallel version of it are used. Different parallelization variants of feature subset selection (fss) are presented and their accuracy and computation time are also evaluated on four different datasets. The comparison is performed among different parallelization variations and the serial implementation of fss with the k-means clustering algorithm. Finally, the results of the research are presented, highlighting the importance of parallelization in reducing the execution time of the proposed algorithms.

IntroductionHidradenitis suppurativa (HS) is a chronic, immune-mediated skin condition characterized by inflammatory lesions that can cause pain, impaired physical activity, and reduced quality of life. This study evaluated the efficacy and safety of risankizumab, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, for the treatment of HS.MethodsThis phase II multicenter, randomized, placebo-controlled, double-blind study investigated the efficacy and safety of risankizumab in patients with moderate-to-severe HS. Patients were randomized 1:1:1 to receive subcutaneous risankizumab 180mg; risankizumab 360mg; or placebo at weeks0, 1, 2, 4, and 12. Patients initially randomized to placebo received blinded risankizumab 360mg at weeks16, 17, and 18; patients initially randomized to risankizumab received blinded matching placebo at the same time points. From weeks20-60, all patients received open-label risankizumab 360mg every 8weeks. The primary endpoint was the achievement of HS Clinical Response (HiSCR) at week16. Safety was assessed by monitoring of treatment-emergent adverse events (TEAEs).ResultsA total of 243 patients were randomized (risankizumab 180mg, n = 80; risankizumab 360mg, n = 81; placebo, n = 82). HiSCR was achieved by 46.8% of patients with risankizumab 180mg, 43.4% with risankizumab 360mg, and 41.5% with placebo at week16. The primary endpoint was not met, and the study was terminated early. Incidence of TEAEs, severe TEAEs, TEAEs considered possibly related to study drug, and TEAEs leading to discontinuation of study drug were generally low and comparable across treatment groups.ConclusionRisankizumab does not appear to be an efficacious treatment for moderate-to-severe HS. Future studies to understand the complex molecular mechanisms underlying HS pathogenesis and develop improved therapies are warranted.Trial registrationClinicalTrials.gov identifier: NCT03926169.

Despite voluminous research on barriers to exporting, knowledge on the inhibiting role of specific obstacles confronted by firms when exporting via cross-border e-commerce (CBEC) is virtually absent. Using data from a cross-industry sample of 1256 firms located in 25 different European countries, we shed light on this issue by examining the organizational determinants and performance outcomes of CBEC barriers. The results revealed these barriers are more evident in the case of firms with smaller size, lacking experience, and having no affiliation with other companies. It was also found that all different types of CBEC barriers, namely financial complexities, coping with foreign markets, supplier restrictions, technical difficulties, and product limitations, are negatively affecting online export performance. Finally, both the home country’s level of digital infrastructure and the foreign market’s Internet penetration rate exhibited a strong moderating effect on the association between CBEC barriers and export performance.

Due to their atomic-scale thickness, handling and processing of two-dimensional (2D) materials often require multistep techniques whose complexity hampers their large-scale integration in modern device applications. Here we demonstrate that the laser-induced forward transfer (LIFT) method can achieve the one-step, nondestructive printing of the prototypical 2D material MoS2. By selecting the optimal LIFT experimental conditions, we were able to transfer arrays of MoS2 pixels from a metal donor substrate to a dielectric receiver substrate. A combination of various characterization techniques has confirmed that the transfer of intact MoS2 monolayers is not only feasible, but it can also happen without incurring significant defect damage during the process. The successful transfer of MoS2 shows the broad potential the LIFT technique has in the emerging field of printed electronics, including printed devices based on 2D materials.

The world is currently facing the problem of the lack of education in basic education for students with intellectual disabilities. Therefore, it is important to follow up and monitor the various learning software that helps to address this problem. The study carried out is a review of scientific literature, which gathers research and studies, through a search in several databases: Dialnet, EBSCO, ERIC, IEEE Xplore, Redalyc, SAGE, ScienceDirect, Scopus, and Wiley. Likewise, according to certain previously defined inclusion and exclusion criteria, a total of two hundred (200) scientific articles were systematized, showing the digital technologies that facilitate the control, follow-up, and monitoring of the education of these students.

BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses.ResultsWe confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31).ConclusionsWe show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

The devices that people use every day, such as mobile phones and wireless networks, emit electromagnetic waves in the radio frequency range. The widespread use of these devices, as well as the change in people’s social behavior, have dramatically increased their exposure to electromagnetic radiation. Due to the rapid increase of young people users, public health officials and the scientific community are showing particular interest in the possible effects of electromagnetic radiation on human health. Many researchers express strong concerns about the effects of exposure to electromagnetic radiation, as it can have a serious impact on physical, cognitive, and social health. This study focused on self-reported health problems after excessive talking time on mobile phones of 619 (n=619) University students of both genders, in the age group of 18-24 years were randomly selected. The data was collected using a close-ended questionnaire. Headache was found to be the most frequently reported symptom (69%) followed by pressure in the head (38.8%). In most self-reported health problems no correlation was found between the genders. Female students tend to talk more on their mobile phones, and it was found that this extensive use was associated with the declaration of more self-reported health problems. The results of this study do not leave us any room for complacency, especially when we talk about health issues, and continuous research is needed to protect people’s health. In addition, modern education should provide the necessary knowledge to students, but also take care of the development of the critical thinking of future citizens, so that they can make the most appropriate decisions for their health.

Pulmonary embolism (PE) following trauma is a potentially preventable but highly lethal complication. We sought to investigate the incidence, risk factors and potential timing of occurrence of post-traumatic PE in a large cohort of trauma fatalities.A case-control study on 9266 consecutive trauma fatalities (between 1996 and 2005) from a regional autopsy-based trauma registry. Injuries were classified according to the Abbreviated Injury Scale-1990 edition (AIS-90) and the Injury Severity Score (ISS) was calculated. Hospitalized victims were categorized according to the presence or absence of PE on autopsy. Univariate comparisons and multivariate logistic regression analysis for probabilities of association (odds ratios-OR) were performed.Out of 2705 subjects who met the inclusion criteria, 116 had autopsy findings of PE and constituted the PE group (incidence of 4,3%), while the remaining victims formed the control group. The survival time of the PE group ranged from 0.66 to 104.73 days. Victims in the PE group were older (median age 69.5 vs 59), had lower ISS values (median 16 vs 26) and longer post-injury survival times (median 13.6 vs 5.7 days). Positively associated risk factors were AIS2-5 pelvic ring injuries (OR:2.23) and secondary deaths following an uneventful hospital discharge (OR:3.97), while AIS2-5 head (OR:0.33) and abdominal injuries (OR:0.23) showed a reverse association.Trauma fatalities with autopsy findings of PE were associated with less severe trauma indicating that PE was likely detrimental to the fatal outcome. Both the early and delayed occurrence of PE was reaffirmed. Prophylactic measures should be initiated promptly and extended post discharge for high risk patients to prevent secondary deaths.

State-of-the-art Earth system models typically employ grid spacings of O(100 km), which is too coarse to explicitly resolve main drivers of the flow of energy and matter across the Earth system. In this paper, we present the new ICON-Sapphire model configuration, which targets a representation of the components of the Earth system and their interactions with a grid spacing of 10 km and finer. Through the use of selected simulation examples, we demonstrate that ICON-Sapphire can (i) be run coupled globally on seasonal timescales with a grid spacing of 5 km, on monthly timescales with a grid spacing of 2.5 km, and on daily timescales with a grid spacing of 1.25 km; (ii) resolve large eddies in the atmosphere using hectometer grid spacings on limited-area domains in atmosphere-only simulations; (iii) resolve submesoscale ocean eddies by using a global uniform grid of 1.25 km or a telescoping grid with the finest grid spacing at 530 m, the latter coupled to a uniform atmosphere; and (iv) simulate biogeochemistry in an ocean-only simulation integrated for 4 years at 10 km. Comparison of basic features of the climate system to observations reveals no obvious pitfalls, even though some observed aspects remain difficult to capture. The throughput of the coupled 5 km global simulation is 126 simulated days per day employing 21 % of the latest machine of the German Climate Computing Center. Extrapolating from these results, multi-decadal global simulations including interactive carbon are now possible, and short global simulations resolving large eddies in the atmosphere and submesoscale eddies in the ocean are within reach.

El material concreto formaliza y potencia el conocimiento intuitivo que poseen los estudiantes dentro de su realidad de cálculo. Para su desarrollo cognitivo es importante aplicar las tres etapas: concreta o manipulativa, pictórica o representación gráfica, para luego manejar de manera apropiada la fase abstracta o simbólica. Se hace una reflexión del material concreto como una verdadera alternativa a la comprensión de conceptos matemáticos y se identifica criterios de clasificación para los mismos. Se puede concluir que frente a las investigaciones realizadas sobre el pensamiento matemático evidencian que uno de los problemas latentes en la actualidad es la utilización de una metodología pasiva que los maestros practican dentro del aula, generando un aprendizaje poco significativo, por lo que se hace urgente generar un cambio de metodología en el tratamiento de la matemática para crear puentes que permitan pasar de procedimientos primitivos que poseen los niños a procedimientos previamente elaborados que permitan la construcción de aprendizajes duraderos.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications–driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.

Two recent, high-profile manuscripts reported negative results with two parallel approaches of passive immunization targeting α-synuclein in a population of patients with early Parkinson's disease (PD). These phase II studies failed to show a bona fide disease-modifying neuroprotective effect on PD progression, despite the evidence that these antibodies effectively bind native α-synuclein in human serum. Here, we discuss the possible reasons that could help explain the lack of clinical efficacy. In particular, we highlight (1) the wealth of evidence supporting the notion of α-synuclein as a valid therapeutic target; (2) the lack of evidence of target engagement in the aforementioned studies, especially of the elusive oligomeric species, the likely culprits in disease pathogenesis and/or its propagation; (3) the limitations, especially in terms of timing passive immunization, of preclinical models, where the same α-synuclein antibodies succeeded in mitigating disease manifestations; (4) the consideration of possibly intervening at an even earlier stage of disease in future trials; and (5) the multitude of strategies beyond passive immunization that could be used to combat α-synuclein-mediated neurodegeneration, if in the end the current approach is not fruitful. Overall, our perception is that converging developments in the field, among them novel bioassays and biomarkers, improved cellular and animal models and objective measurements of motor activities integrated into clinical trials, if further optimized, will gradually move the momentum of the field forward. This, to better test the concept of whether α-synuclein-targeting therapies can indeed deliver the "holy grail" of neuroprotection to the benefit of the PD community. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63–17.21]} and female sex [OR 2.46 (CI 1.19–5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [−2.22 kg (95% CI −2.79 to −1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [−0.36% (95% CI −0.51 to −0.21)], serum uric acid [−0.44 mg/dl (95% CI −0.60 to −0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11–0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28–0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Here, we report synergistic nanostructured surfaces combining bactericidal and bacteria-releasing properties. A polystyrene

Metanephrines (MTNs) are metabolites of catecholamines and are constantly produced in high amounts by pheochromocytomas and paragangliomas (PPGLs). Marked MTN elevations ( 3 times the upper limit of normal [ULN]) are highly suggestive of PPGL. The frequency of marked MTN elevations in non-PPGL hypertensive emergencies (HTNEs) is unknown.We retrospectively analyzed plasma free metanephrine (PMTN) and 24-h urinary fractionated metanephrine (UMTN) levels in 48 consecutive patients (59.7 ± 15.6 years; 48% female; BMI: 31 ± 9.7 kg/mPMTN/UMTN levels were not associated with SBP/DBP, comorbidities, end-organ damage, or interfering medications, the exception being that plasma normetanephrines (PNMNs) were significantly associated with comorbidities (Adj. RMarked MTN elevations in HTNE are uncommon. Therefore, we recommend against measuring MTN in the setting of an apparent precipitating cause of HTNE to avoid unnecessary testing and imaging. Testing for MTN in HTNE should be pursued only when there is no clear precipitating cause and in cases where there is strong underlying clinical suspicion for PPGL. However, should testing be performed, marked MTN elevations should not be disregarded as being a commonly occurring result of HTNE.

Recientemente ha tomado un creciente interés el estudio del talento humano para la comprensión del desarrollo empresarial. Un adecuado entorno laboral favorece al óptimo desempeño de los trabajadores en sus labores. De este modo, el clima organizacional representa un aspecto clave para el estudio de las pymes del sector comercial de Ayacucho, Perú. El objetivo de este trabajo es describir el clima organizacional en las pymes del sector comercio en la ciudad de Ayacucho. La investigación es cuantitativa y de tipo descriptivo, para la cual se aplicó un cuestionario tipo Likert a 176 trabajadores de distintas organizaciones comerciales. Los resultados arrojan que la gran mayoría de los trabajadores de estas empresas perciben un clima organizacional medianamente bueno con tendencia a malo, evidenciando debilidades en aspectos claves tales como la flexibilidad organizacional, la comunicación eficaz y el adecuado entorno laboral. Se concluye que es necesario que los directores de estas organizaciones diseñen estrategias para mejorar la percepción del clima organizacional y favorecer de esta manera el desarrollo exitoso del desempeño empresarial de los miembros que forman parte de la organización.

Lisfranc injuries result when the bones or ligaments that support the midfoot are torn, and the classifications of these injuries are based on the coronal displacement of the metatarsals. On the saggital plane, the first metatarsal is usually dorsally dislocated due to dorsal ligament weakness. We present a case report of a 29-year-old woman who sustained a Lisfranc injury of her right foot with plantar subluxation of the first metatarsal, which was treated with open reduction and internal fixation of the first metatarsal and fusion of the second metatarsal.

This study was aimed at assessing the effectiveness of digital platforms in promoting human resources recruitment process in public entities. Specifically this study focused on four digital platforms commonly used in Tanzania including websites, portal and job boards. This study used a descriptive survey design method in order to achieve the study purpose, in which the study area was TANESCO administrative areas of Ilemela and Nyamagana districts, and the study population was employees of TANESCO from different levels. In this study, Krejcie and Morgan, (1970) table was adopted in sample size determination in which the optimum sample size was 152 from the study population of 248. Questionnaire method was used for data collection whereby quantitative data collected through the method were analyzed using descriptive statistics, correlation analysis, multiple regression analysis and ANOVA with the aid of Statistical Package for Social Science (SPSS version 23.0). Multiple regression analysis findings indicated that website, portal and job boards have positive significance influence on recruitment process. In contrary, social media has positive influence on recruitment process, however the effect was not supported by statistical significance. This study concluded that digital platforms including websites, portal and job boards are very effective in promoting recruitment process in public entities. This study strongly recommend that public entities should deploy digital platforms in recruitment process as it is evident that digital platforms has enormous contribution to the effectiveness of recruitment process. In addition, qualified employees should control digital platforms with much emphasize on transparency, integrity and adherence to the code of conduct. This will enable public entities realize the benefits of using digital recruitment.

Developing efficient and stable organic photovoltaics (OPVs) is crucial for the technology's commercial success.

Immune checkpoint inhibitors (ICI) have transformed the treatment of melanoma. However, the majority of patients have primary or acquired resistance to ICIs, limiting durable responses and patient survival. IFNγ signaling and the expression of IFNγ-stimulated genes correlate with either response or resistance to ICIs, in a context-dependent manner. While IFNγ-inducible immunostimulatory genes are required for response to ICIs, chronic IFNγ signaling induces the expression of immunosuppressive genes, promoting resistance to these therapies. Here, we show that high levels of Unc-51 like kinase 1 (ULK1) correlate with poor survival in patients with melanoma and overexpression of ULK1 in melanoma cells enhances IFNγ-induced expression of immunosuppressive genes, with minimal effects on the expression of immunostimulatory genes. In contrast, genetic or pharmacologic inhibition of ULK1 reduces expression of IFNγ-induced immunosuppressive genes. ULK1 binds IRF1 in the nuclear compartment of melanoma cells, controlling its binding to the programmed death-ligand 1 promoter region. In addition, pharmacologic inhibition of ULK1 in combination with anti-programmed cell death protein 1 therapy further reduces melanoma tumor growth in vivo. Our data suggest that targeting ULK1 represses IFNγ-dependent immunosuppression. These findings support the combination of ULK1 drug-targeted inhibition with ICIs for the treatment of patients with melanoma to improve response rates and patient outcomes. Implications: This study identifies ULK1, activated downstream of IFNγ signaling, as a druggable target to overcome resistance mechanisms to ICI therapy in metastatic melanoma.