Zolpidem improves task-specific dystonia: A randomized clinical trial integrating exploratory transcranial magnetic stimulation and [18F] FDG-PET imaging.

BACKGROUND: Task-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability - active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. RESULTS: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. CONCLUSIONS: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.

Sex Differences in Dystonia.

BACKGROUND: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms. OBJECTIVES: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences. METHODS: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias. RESULTS: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A). CONCLUSIONS: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics.

Quantifying abnormal writing kinematics in writer's cramp using a novel software platform.

BACKGROUND: Writer's cramp is a task-specific focal hand dystonia, which is diagnosed clinically. Quantification of defect in WC is done using clinical scales, while digitized platforms are lacking. OBJECTIVE: To design and test a platform that can differentiate and quantify the abnormal kinematics of writing using a software interface and to validate it in adult-onset isolated writer's cramp (WC). METHODS: A native platform was designed using Java and Wacom Intuos pro tablet and the data analyzed using a MATLAB-based platform called Large Data-Based Evaluation of Kinematics in Handwriting (LEKH). We standardized this new platform by comparing the handwriting between patients with WC and age, and gender and education-matched healthy controls, using standard tasks to assess the kinematics. RESULTS: Comparison of the writing of right-handed WC patients (N = 21) and 39 healthy controls (N = 39) showed that patients differed from controls in the frequency of strokes (P < 0.001), number of inversions of velocity (P < 0.001), number of breaks (P = 0.02), air time and paper time (P < 0.001). CONCLUSIONS: Using the LEKH platform, the kinematic profile of patients with WC could be differentiated from healthy controls. Studies in larger samples will be needed to derive statistical models that can differentiate the flexion and extension types of WC which can help in muscle selection and to quantify the effects of treatment.

Does the guidance method affect the doses of botulinum toxin in writer's cramp?

PURPOSE: Botulinum neurotoxin (BoNT) injections are the main medical treatment of writer's cramp. When the outcome is favourable, patients usually receive injections several times per year in the long-term. However, we know little about the course of BoNT doses and nothing about the impact of the guidance method on the clinical outcome or injection strategy. METHODS: We studied, in the long-term, the doses of BoNT and the target muscles in a group of patients with writer's cramp, according to the guidance method (electrical stimulation or ultrasound). Patients received at least three injection cycles guided by electrical stimulation, followed by at least three injection cycles guided by ultrasound. RESULTS: Twenty-four patients were included. More target muscles were injected after switching to ultrasound guidance, especially the flexor carpi ulnaris and the flexor carpi radialis. The mean dose by muscle was lower when ultrasound guidance was used. When using electrical stimulation guidance, the dose in the flexors of the fingers decreased in the long-term, but increased in the flexors of the wrist. The course of the BoNT doses and of the number of target muscles per cycle were not the same during the first period (electrical stimulation) and the second period (ultrasound). CONCLUSIONS: Switching to ultrasound guidance, the BoNT dose decreased, mainly in the flexors of the wrist. Based on the results of our study, we suggest a starting dose in several muscles (flexor carpi ulnaris, flexor carpi radialis, flexor digitorum profundus and flexor pollicis longus).

Writer's Cramps as an Initial Symptom of Spinocerebellar Ataxia Type 14: A Case Report.

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxia caused by mutations in PRKCG. We herein report a case of SCA14 presenting with writer's cramp that predated the onset of progressive ataxia by four years. A 47-year-old Japanese woman had an 11-year history of writer's cramps, followed by unsteadiness. Whole-exome sequencing revealed a heterozygous mutation in PRKCG (p.C142S), leading to an SCA14 diagnosis. Therefore, writer's cramp might be a characteristic extracerebellar sign of SCA14 and can precede the onset of cerebellar ataxia.

Un encuentro inesperado: evocando a José María Arguedas durante su paso por la Asistencia Pública de Grau / Um encontro inesperado: evocar José María Arguedas durante a sua passagem pelo Centro de Assistência Pública de Grau / An unexpected encounter: evoking José María Arguedas during his stay at the Grau Public Assistance Health Center

The present article contributes with additional information, until now very little known, from the moment when the great Peruvian writer José María Arguedas, wounded of death product of had been inflicted with a bullet in the head which provoked him to be transferred from the National Agrarian University towards the Employee's Hospital. On the way, it is noted that a stop was made, until now scarcely known, that happened in the Post of the Grau Public Assistance Health Center, in the afternoon of Friday November 28, 1969. That day, as a consequence of a strong intestinal infection, the author of this article was being treated in the same Health Center, finding himself sharing the same room, during that time with the alleged writer.(AU)

El presente artículo contribuye con información adicional, hasta ahora muy poco conocida, cuando el gran escritor peruano José María Arguedas, herido de muerte producto de haberse infligido un balazo en la cabeza es trasladado desde la Universidad Nacional Agraria hacia el Hospital del Empleado. En el trayecto, se hace notar que se hizo una escala, hasta ahora escasamente conocida, que ocurrió en el Puesto de la Asistencia Pública de Grau, en la tarde del viernes 28 de noviembre de 1969. Ese día a consecuencia de una fuerte infección intestinal, el autor del presente artículo fue atendido de emergencia en la Asistencia Pública de Grau, compartiendo la misma habitación, durante el tiempo que permaneció el escritor en aquel centro asistencial de salud.(AU)

Este artigo contribui com informações adicionais, até agora pouco conhecidas, quando o grande escritor peruano José María Arguedas, mortalmente ferido por ter levado um tiro na cabeça, é transferido da Universidade Nacional Agrária para o Hospital do Empregado. No caminho, nota-se que foi feita uma escala, até agora pouco conhecida, que ocorreu no Posto de Atendimento Público de Grau, na tarde de sexta-feira, 28 de novembro de 1969. Naquele dia em consequência de uma forte infecção intestinal, o autor deste artigo foi atendido no pronto-socorro da Assistência Pública do Grau, compartilhando o mesmo quarto, durante o tempo que o escritor permaneceu naquele centro de saúde.(AU)

Recent Advances in RNA m6A Modification in Solid Tumors and Tumor Immunity.

An analogous field to epigenetics is referred to as epitranscriptomics, which focuses on the study of post-transcriptional chemical modifications in RNA. RNA molecules, including mRNA, tRNA, rRNA, and other non-coding RNA molecules, can be edited with numerous modifications. The most prevalent modification in eukaryotic mRNA is N6-methyladenosine (m6A), which is a reversible modification found in over 7000 human genes. Recent technological advances have accelerated the characterization of these modifications, and they have been shown to play important roles in many biological processes, including pathogenic processes such as cancer. In this chapter, we discuss the role of m6A mRNA modification in cancer with a focus on solid tumor biology and immunity. m6A RNA methylation and its regulatory proteins can play context-dependent roles in solid tumor development and progression by modulating RNA metabolism to drive oncogenic or tumor-suppressive cellular pathways. m6A RNA methylation also plays dynamic roles within both immune cells and tumor cells to mediate the anti-tumor immune response. Finally, an emerging area of research within epitranscriptomics studies the role of m6A RNA methylation in promoting sensitivity or resistance to cancer therapies, including chemotherapy, targeted therapy, and immunotherapy. Overall, our understanding of m6A RNA methylation in solid tumors has advanced significantly, and continued research is needed both to fill gaps in knowledge and to identify potential areas of focus for therapeutic development.

A cross-cultural, cross-disciplinary, and cross-gender study on Appraisal resources in PhD dissertation abstracts: Martin & White's (2005) Appraisal Theory in focus.

The abstract which complements proposals, articles, and dissertations, is a remarkable convention in scientific studies since it creates access for readers and authors to read or publish studies or articles. Research abstracts (RA) function as the gateway to view an article, journals' selection for contributions, and for conferences to accept or reject articles (Lores, 2004) In this study, we aimed to investigate the preferences of writers in 160 PhD dissertation abstracts, encompassing both male and female native and non-native authors, across various fields of study, both in the hard and soft sciences. Our primary objective was to discern the writers' inclinations towards utilizing specific linguistic resources, as proposed by Martin and White's Appraisal theory (2005), to convey their positions and engage with the perspectives articulated by their peers. The analysis of the data, conducted using statistical methods, unveiled a pervasive utilization of appraisal resources by the writers, enabling them to articulate their viewpoints, prospects, perceptions, and evaluations concerning diverse subjects. Among these resources, Attitude resources stood out prominently, constituting a substantial 84% of the total Appraisal resources employed in all the abstracts. Graduation resources held an intermediate position, while Engagement resources were the least utilized. Within the realm of Attitude subcategories, Appreciation resources emerged as the most prevalent. Remarkably, female authors specializing in the soft sciences displayed a higher degree of proficiency in the use of these resources, surpassing their counterparts in other categories. This finding suggests that female writers in the soft sciences possess exceptional interpersonal communication skills, making them particularly persuasive and inspirational. The implications of this study extend to the domains of language teaching and learning, material development, and syllabus design. It sheds light on how writers employ linguistic resources to convey their positions effectively, offering valuable insights for educational practices and curriculum enhancement.

Literature citation and writer identity construction in linguistic academic discourse.

This study revealed the distributional features of literature citation and writer identity in linguistic academic discourse, and further explored how writer identity is constructed through literature citation. Based on Petric's citation typology and Ivanic's writer identity framework, the study investigated various types of citations and identities in thirty journal articles published in the Journal of English for Academic Purposes from 2017 to 2021. The results showed that there are a total of 1637 citation instances, among which the dominant type is attribution citation (36.59 %). Besides, the study revealed that 80.45 % of the total citations construct discoursal self only and 19.55 % reveal both discoursal self and authorial self. In terms of discoursal self, writers present themselves as a member of academic community, a contributor to a field of knowledge, a knowledgeable and professional scholar, and a reliable and credible writer. As for authorial self, they would like to position themselves to be a writer with authority and an evaluator. It is expected that the current study can help novice writers use citations strategically and establish their desired identity accordingly.

Deep Learning-Based Child Handwritten Arabic Character Recognition and Handwriting Discrimination.

Handwritten Arabic character recognition has received increasing research interest in recent years. However, as of yet, the majority of the existing handwriting recognition systems have only focused on adult handwriting. In contrast, there have not been many studies conducted on child handwriting, nor has it been regarded as a major research issue yet. Compared to adults' handwriting, children's handwriting is more challenging since it often has lower quality, higher variation, and larger distortions. Furthermore, most of these designed and currently used systems for adult data have not been trained or tested for child data recognition purposes or applications. This paper presents a new convolution neural network (CNN) model for recognizing children's handwritten isolated Arabic letters. Several experiments are conducted here to investigate and analyze the influence when training the model with different datasets of children, adults, and both to measure and compare performance in recognizing children's handwritten characters and discriminating their handwriting from adult handwriting. In addition, a number of supplementary features are proposed based on empirical study and observations and are combined with CNN-extracted features to augment the child and adult writer-group classification. Lastly, the performance of the extracted deep and supplementary features is evaluated and compared using different classifiers, comprising Softmax, support vector machine (SVM), k-nearest neighbor (KNN), and random forest (RF), as well as different dataset combinations from Hijja for child data and AHCD for adult data. Our findings highlight that the training strategy is crucial, and the inclusion of adult data is influential in achieving an increased accuracy of up to around 93% in child handwritten character recognition. Moreover, the fusion of the proposed supplementary features with the deep features attains an improved performance in child handwriting discrimination by up to around 94%.

Dialogic literary argumentation and close reading: effects on high school students' literature-related argumentative writing and motivational beliefs.

Given evidence that adolescent students' motivation to read and write about literature declines with age, we proffer an approach called dialogic literary argumentation (DLA) that asks students to explore literature through argumentation in pursuit of understanding the meanings and possibilities of being human. This quasi-experimental study compared the effectiveness of DLA with close reading (CR), a common approach to teaching literature in high school English language arts classrooms, in improving students' motivational beliefs about writing and literature-related argumentative writing. The study also examined how the links between motivational beliefs and argumentative writing performance varied by instructional contexts. Participants were 278 high school students in 14 classrooms across 8 public high schools. Classrooms of students received either DLA or CR throughout the academic year. While both the DLA and CR groups improved in literature-related argumentative writing, the DLA group demonstrated more growth than the CR group. Neither group exhibited changes in motivational beliefs. However, at the end of the year, both DLA and CR students' transactional writer beliefs were predictive of writing self-efficacy. Transmissional writer beliefs negatively correlated with argumentative writing in the CR group and had a null relationship in the DLA group. Overall, motivational beliefs and argumentative writing were more positively correlated in the DLA group than the CR group after the intervention. We posit that the argumentative elements unique to DLA may act to protect students from the negative impacts of transmissional beliefs. Our findings provide theoretical explanations and pedagogical recommendations on how DLA and CR can be jointly employed to heighten students' motivation and strengthen their argumentative writing competence.

Adult-onset focal dystonias: To lump or split.

The adult-onset focal dystonias are a group of clinically heterogeneous disorders that affect different regions of the body. Although they affect different regions with different clinical manifestations, there is evidence that etiopathogenesis is shared at the anatomical, physiological, and genetic levels. However, there is also evidence that etiopathogenesis varies. This chapter summarizes the evidence for lumping or splitting these apparently different clinical phenotypes. It also includes some potential explanations to explain the similarities and differences.

Thomas Shields Henderson - Brooklyn Dentist and Irish Nationalist.

An unusual card advertising the dental services of T.S. Henderson revives the story of an Irish dentist who left his homeland and came to Brooklyn, New York to practice. He was a fervent Irish Nationalist and was active in Irish causes. Henderson was an abuser of alcohol and eventually found dead in Albany, New York. The death was considered a suicide, but was it?

Mechanisms of NAT10 as ac4C writer in diseases.

In the early stage, N4-acetylcytidine (ac4C) was regarded as a conservative nucleoside present on tRNA and rRNA. Recently, studies have shown that ac4C also exists in human and yeast mRNA. N-Acetyltransferase-like protein 10 (NAT10) is the first enzyme to be found to catalyze ac4C production in eukaryotic RNA and has acetyltransferase activity and RNA-binding activity. Here, we first describe the structure and cellular localization of NAT10. Then, we conclude the active roles of NAT10 as the ac4C "writer" in mRNA stability and translation efficiency, oocyte maturation, bone remodeling, and fatty acid metabolism. With respect to disease, we focused on the promoting functions of NAT10 in proliferation, metastasis, and apoptosis in multiple tumors. The immune regulatory role of NAT10 in systemic lupus erythematosus and the maintenance role of NAT10 in virus RNA stability and replication in influenza A virus are also introduced. This review identifies NAT10 as a potential target for diagnosis, therapy, and prognosis in clinical application.

The role of regulators of RNA m6A methylation in lung cancer.

N6-methyladenosine (m6A) modification is found the most prevalent and abundant post-transcriptional mRNA modification in eukaryotic cells. It regulates almost all stages of RNA life cycle including splicing, translocation, stability, decay and translation. As a dynamic and reversible process, m6A modification is catalyzed by the RNA methyltransferases ('writers'), removed by the demethylases ('erasers'), and interacts with m6A-binding proteins ('readers'). Recent studies have revealed that these m6A modification regulators are frequently expressed aberrantly in various types of cancer, and involved in cell proliferation, differentiation, metabolism, particularly, in tumorigenesis and tumor progression through diverse mechanisms. In this review, the m6A modification process and its regulatory functions in lung cancer are summarized. Furthermore, the research progress in the inhibitor development of m6A modification, and the potential of targeting m6A modifying proteins for clinical application are discussed.

A novel scoring model based on RNA modification "writers" can predict the prognosis and guide immunotherapy in gastric cancer.

Although extensive research has been carried out on the epigenetic regulation of single RNA modifications in gastric cancer, little is known regarding the crosstalk of four major RNA adenosine modifications, namely, m6A, m1A, alternative polyadenylation and adenosine-to-inosine RNA editing. By analyzing 26 RNA modification "writers" in 1750 gastric cancer samples, we creatively constructed a scoring model called the "Writers" of the RNA Modification Score (WRM_Score), which was able to quantify the RNA modification subtypes of individual patients. In addition, we explored the relationship between WRM_Score and transcriptional and posttranscriptional regulation, tumor microenvironment, clinical features and molecular subtypes. We constructed an RNA modification scoring model including two different subgroups: WRM_Score_low and WRM_Score_high. The former was associated with survival benefit and good efficacy of immune checkpoint inhibitors (ICIs) due to gene repair and immune activation, while the latter was related to poor prognosis and bad efficacy of ICIs because of stromal activation and immunosuppression. The WRM score based on immune and molecular characteristics of the RNA modification pattern is a reliable predictor of the prognosis of gastric cancer and the therapeutic efficacy of immune checkpoint inhibitors in gastric cancer.

Reflections on Losing My Office during the Pandemic.

Reflections on loss, grief, and the possibility of recovery after losing my office, my analyst's office, and my analyst during the pandemic. The role of an office in consolidating a sense of analytic identity and the usefulness of sadness in catalyzing change are discussed.