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In general, similar to FDA and other health authorities, the PMDA requires clinical efficacy study(ies) to evaluate equivalence between a reference biological product and a Biosimilar product for new drug applications. Even if an identical clinical efficacy study is included in both of PMDA and FDA submissions, the coefficients of confidence interval (CI) used for comparison with the equivalence margins could be different between the two submissions (e.g., 95% CI vs. 90% CI). In this article, we will focus on clinical efficacy studies of Biosimilar products and provide an overview of the two one-sided tests (TOST) and the type I error rate for equivalence design. Then, we summarize published PMDA review reports of Biosimilar products in terms of the coefficients of CI and other elements of the primary endpoints, and explain some Japanese guidelines of Biosimilar and Statistics behind the difference between PMDA and FDA submissions. In addition, we discuss how to use statistical methods correctly and efficiently for PMDA submissions.Disorders of thyroid function are among the commonest referrals to endocrinology. While interpretation of thyroid function testing is usually straightforward, accurate interpretation becomes significantly more challenging when the parameters do not behave as would be expected in normal negative feedback. In such cases, uncertainty regarding further investigation and management arises. An important abnormal pattern encountered in clinical practice is that of high normal or raised free thyroxine (fT4) with inappropriately non-suppressed or elevated thyroid-stimulating hormone (TSH). In this short review using two clinical vignettes, we examine the diagnostic approach in such cases. DDD86481 chemical structure A diagnostic algorithm is proposed to ensure that a definitive diagnosis is reached in these challenging cases.One of the two miscomputations identified in the infoVal metric, namely the omission of the k constant, turns out not to be a miscomputation, since the constant was already taken into account by default in the mad() function from R (see https//www.rdocumentation.org/packages/stats/versions/3.6.2/topics/mad).We present Titta, an open-source toolbox for controlling eye trackers manufactured by Tobii AB from MATLAB and Python. The toolbox provides a wrapper around the Tobii Pro SDK, providing a convenient graphical participant setup, calibration and validation interface implemented using the PsychToolbox and PsychoPy toolboxes. The toolbox furthermore enables MATLAB and Python experiments to communicate with Tobii Pro Lab through the TalkToProLab tool. This enables experiments to be created and run using the freedom of MATLAB and Python, while the recording can be visualized and analyzed in Tobii Pro Lab. All screen-mounted Tobii eye trackers that are supported by the Tobii Pro SDK are also supported by Titta. At the time of writing, these are the Spectrum, Nano, TX300, T60XL, X3-120, X2-60, X2-30, X60, X120, T60 and T120 from Tobii Pro, and the 4C from Tobii Tech.The verbal fluency task-listing words from a category or words that begin with a specific letter-is a common experimental paradigm that is used to diagnose memory impairments and to understand how we store and retrieve knowledge. Data from the verbal fluency task are analyzed in many different ways, often requiring manual coding that is time intensive and error-prone. Researchers have also used fluency data from groups or individuals to estimate semantic networks-latent representations of semantic memory that describe the relations between concepts-that further our understanding of how knowledge is encoded. However computational methods used to estimate networks are not standardized and can be difficult to implement, which has hindered widespread adoption. We present SNAFU the Semantic Network and Fluency Utility, a tool for estimating networks from fluency data and automatizing traditional fluency analyses, including counting cluster switches and cluster sizes, intrusions, perseverations, and word frequencies. In this manuscript, we provide a primer on using the tool, illustrate its application by creating a semantic network for foods, and validate the tool by comparing results to trained human coders using multiple datasets.Unlike complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT) (i.e., Lesch-Nyhan syndrome), partial HPRT deficiency causes HPRT-related hyperuricemia without neurological symptoms. Herein, we describe a 22-year-old man without neurological symptoms that presented gout, hyperuricemia (serum urate level, 12.2 mg/dL), multiple renal microcalculi, and a family history of juvenile gout that was exhibited by his brother and grandfather. Genetic testing revealed a novel missense mutation, c.103G>A (p.V35M), in the HPRT1 gene, and biochemical testing (conducted using the patient's erythrocytes) showed that the patient retained only 12.4% HPRT enzymatic activity compared to that exhibited by a healthy control subject. We thus diagnosed the patient with HPRT-related hyperuricemia caused by partial HPRT deficiency. After his serum urate level was controlled via treatment with febuxostat, his gout did not recur. Thus, this study emphasizes that HPRT deficiency should be considered as a potential cause of familial juvenile gout, even in the absence of neurological symptoms.Exposure to cadmium (Cd) is a risk factor to health impairments, wherein its cytotoxicity is attributed to induction of oxidative stress. Usage of anti-oxidants, however, can help lessen the damaging effects of Cd. The effect of Cd interaction with low concentration of dietary anti-oxidants, L-ascorbic acid and (-)-epigallocatechin gallate (EGCG), to PC12 cellular mechanisms was examined. The expected toxicity of Cd was observed on PC12 cells but addition of L-ascorbic acid ameliorated this effect. On the other hand, addition of EGCG was able to increase the cytotoxicity of Cd and to decrease the protective effect of L-ascorbic acid against Cd. Increase in LDH activity and decrease in free sulfhydryl levels indicated cell membrane damage and oxidative stress, respectively, in Cd- and EGCG-Cd-treated cells. Downregulation of pro-apoptotic proteins (pro-caspase-9, p53, and ERK1) was observed in cells treated with Cd alone and EGCG-Cd, while upregulation of autophagy-linked proteins (p62 and pBeclin1) was found on L-ascorbic acid-Cd combination treatments.