Probable fluoxetine-induced hepatomegaly: a case report

Depressive disorder is a common behavioural, psychiatric disorder. Among various antidepressants selective serotonin reuptake inhibitors (SSRIs) are preferred drugs for the treatment of depression. When second-generation antidepressants SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat depression, 0.5–1% of patients develop mildly altered liver function without any symptoms. Various degrees of organ dysfunction are linked with drug-induced liver injury, which is unpredictable and might result from exposure to a drug. We reported suspected fluoxetine-induced hepatomegaly secondary to nine weeks of treatment with an SSRI fluoxetine. Upon cessation of the agent, the patient recovered symptomatically. The evidence is vital that the hepatomegaly in this patient was caused by fluoxetine

A First-Order Explicit-Implicit Splitting Method for a Convection-Diffusion Problem

We analyze a second-order in space, first-order in time accurate finite difference method for a spatially periodic convection-diffusion problem. This method is a time stepping method based on the first-order Lie splitting of the spatially semidiscrete solution. In each time step, on an interval of length k, of this solution, the method uses the backward Euler method for the diffusion part, and then applies a stabilized explicit forward Euler approximation on m >= 1 intervals of length k/m for the convection part. With h the mesh width in space, this results in an error bound of the form C(0)h(2) + C(m)k for appropriately smooth solutions, where C-m <= C\u27 + C-\u27\u27/m. This work complements the earlier study [V. Thomee and A. S. Vasudeva Murthy, An explicit- implicit splitting method for a convection-diffusion problem, Comput. Methods Appl. Math. 19 (2019), no. 2, 283-293] based on the second-order Strang splitting

MalFake: A Multimodal Fake News Identification for Malayalam using Recurrent Neural Networks and VGG-16

The amount of news being consumed online has substantially expanded in recent years. Fake news has become increasingly common, especially in regional languages like Malayalam, due to the rapid publication and lack of editorial standards on some online sites. Fake news may have a terrible effect on society, causing people to make bad judgments, lose faith in authorities, and even engage in violent behavior. When we take into the context of India, there are many regional languages, and fake news is spreading in every language. Therefore, providing efficient techniques for identifying false information in regional tongues is crucial. Until now, little to no work has been done in Malayalam, extracting features from multiple modalities to classify fake news. Multimodal approaches are more accurate in detecting fake news, as features from multiple modalities are extracted to build the deep learning classification model. As far as we know, this is the first piece of work in Malayalam that uses multimodal deep learning to tackle false information. Models trained with more than one modality typically outperform models taught with only one modality. Our study in the Malayalam language utilizing multimodal deep learning is a significant step toward more effective misinformation detection and mitigation

Does microsomal glycerophosphate acyltransferase also catalyze the acylation of dihydroxyacetone phosphate?

Rat liver microsomal dihydroxyacetone phosphate acyltransferase, in contrast to the glycerophosphate acyltransferase, was found to be active at low pH (5.5), stable towards heat (55 [deg]C, 15 min) and trypsin (in the absence of detergents) and was not inhibited by high concentrations of N-ethyl maleimide. Dihydroxyacetone phosphate acyltransferase is only slightly and non-competitively inhibited by sn-glycerol-3-phosphate whereas glycerophosphate acyltransferase is strongly inhibited by dihydroxyacetone phosphate in a competitive manner. Kinetic analysis indicates that this competitive inhibition is not due to the competition of two common substrates for the same active center of one enzyme. These results demonstrate that microsomal glycerophosphate acyltransferase and dihydroxyacetone phosphate acyltransferase are two distinct and separate enzymes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24662/1/0000075.pd

Properties of the enzymes catalyzing the biosynthesis of lysophosphatidate and its ether analog in cultured fibroblasts from Zellweger syndrome patients and normal controls

The activities, properties, and steady-state kinetics of the five enzymes catalyzing the synthesis of 1-acyl- and 1-alkyl-sn-glycerol 3-phosphate in the cultured skin fibroblasts from Zellweger syndrome patients and normal controls were studied in detail. Judging from their Km and Vmax values, glycerol phosphate acyltransferase (EC 2.3.1.15), acyl/ alkyl dihydroxyacetone phosphate reductase (EC 1.1.1.101), and acyl coenzyme A reductase (long-chain alcohol forming), appear to be affected only slightly by the absence of peroxisomes characteristic of the Zellweger syndrome. Glycerophosphate acyltransferase also showed no differences in N-ethylmaleimide sensitivity nor in inhibition by dihydroxyacetone phosphate between these cell types. Dihydroxyacetone phosphate acyltransferase (EC 2.3.1.42) and alkyl dihydroxyacetone phosphate synthase (EC 2.5.1.26) have altered activity and kinetic constants in homogenates from Zellweger syndrome fibroblasts. Dihydroxyacetone phosphate acyltransferase has similar Km (DHAP) values in both control and Zellweger syndrome cells; however, the value for the Vmax in Zellweger syndrome cells is only 6% of that found in the controls. This is interpreted as indicating that this enzyme is not defective in this disease but is simply present at a depressed level. Also, this enzyme activity has a maximum rate at pH 7.0-7.5 in the mutant cells as opposed to pH 5.4 in the controls. Acylation of dihydroxyacetone phosphate by control cell homogenate was stimulated by N-ethylmaleimide at both pH 5.7 and 7.5 whereas this activity from Zellweger syndrome cells was slightly inhibited at pH 5.7 and strongly inhibited at pH 7.5. In the absence of detergent, dihydroxyacetone phosphate acyltransferase in the Zellweger syndrome cells was much more labile to trypsin than in the control cells. Alkyl dihydroxyacetone phosphate synthase had a slightly higher Km(33 vs 17 [mu]) for palmitoyl dihydroxyacetone phosphate and a lower Vmax (0.07 vs 0.24 mU/mg protein) in the Zellweger syndrome cells as compared to controls. Although this is a substantial decrease in activity, it probably contributes little to the decreased rate of ether lipid synthesis in these cells. The major problem in this respect is apparently the loss of dihydroxyacetone phosphate acyltransferase activity. All of these enzymes, in both control and Zellweger syndrome cell homogenates, are sedimentable by centrifugation at 100,000g. Also, with the exception of dihydroxyacetone phosphate acyltransferase they had similar patterns of inactivation by heat in both cell types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26724/1/0000274.pd

Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo

Chromogranin A (CgA) is a prohormone and granulogenic factor in neuroendocrine tissues with a regulated secretory pathway. The impact of CgA depletion on secretory granule formation has been previously demonstrated in cell culture. However, studies linking the structural effects of CgA deficiency with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not previously been reported. Adrenomedullary content of the secreted adrenal catecholamines norepinephrine (NE) and epinephrine (EPI) was decreased 30–40 % in Chga-KO mice. Quantification of NE and EPI-storing dense core (DC) vesicles (DCV) revealed decreased DCV numbers in chromaffin cells in Chga-KO mice. For both cell types, the DCV diameter in Chga-KO mice was less (100–200 nm) than in WT mice (200–350 nm). The volume density of the vesicle and vesicle number was also lower in Chga-KO mice. Chga-KO mice showed an ~47 % increase in DCV/DC ratio, implying vesicle swelling due to increased osmotically active free catecholamines. Upon challenge with 2 U/kg insulin, there was a diminution in adrenomedullary EPI, no change in NE and a very large increase in the EPI and NE precursor dopamine (DA), consistent with increased catecholamine biosynthesis during prolonged secretion. We found dilated mitochondrial cristae, endoplasmic reticulum and Golgi complex, as well as increased synaptic mitochondria, synaptic vesicles and glycogen granules in Chga-KO mice compared to WT mice, suggesting that decreased granulogenesis and catecholamine storage in CgA-deficient mouse adrenal medulla is compensated by increased VMAT-dependent catecholamine update into storage vesicles, at the expense of enhanced energy expenditure by the chromaffin cell

Outcome of Patients with Localized Prostate Cancer Treated by Radiotherapy After Confirming the Absence of Lymph Node Invasion

doi:10.1093/jjco/hyq03

Giving RSEs a Larger Stage through the Better Scientific Software Fellowship

The Better Scientific Software Fellowship (BSSwF) was launched in 2018 to foster and promote practices, processes, and tools to improve developer productivity and software sustainability of scientific codes. BSSwF's vision is to grow the community with practitioners, leaders, mentors, and consultants to increase the visibility of scientific software production and sustainability. Over the last five years, many fellowship recipients and honorable mentions have identified as research software engineers (RSEs). This paper provides case studies from several of the program's participants to illustrate some of the diverse ways BSSwF has benefited both the RSE and scientific communities. In an environment where the contributions of RSEs are too often undervalued, we believe that programs such as BSSwF can be a valuable means to recognize and encourage community members to step outside of their regular commitments and expand on their work, collaborations and ideas for a larger audience.Comment: submitted to Computing in Science & Engineering (CiSE), Special Issue on the Future of Research Software Engineers in the U