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Mahmood Dowlatabadi is one of the impressive Iranian novelists, especially in the area of climatic literature. "The empty place of Salouch" is his first novel. This novel deserves an extensive investigation in different aspects such as linguistic and literary features, sociological and anthropological studies, and narratology. In the present study, the speed of narration in the novel of "The empty place of Salouch" (through using Jerar Janet’s narratological theory) and the factors which have had a great influence on that have been investigated. The narrative speed and rhythm are one of the most significant components in narration, also one of the most important elements in the form of the plot. The concept of narrative speed reveals how long it has taken for the actions and events to take place in a literary work and regarding this time juncture how much of the book is devoted to them. In most parts of "The empty place of Salouch", the speed is negative, and the narrative speed is slow; but the narrative speed in the whole novel (the main narration) is average since the narrative speed’s increasing and reducing components in this novel are used in a balanced manner, and this feature has caused the adjustment of speed in the whole novel. In fact, the novelist has used certain strategies to increase the motion and to compensate for the lack of motion and the low speed of narration in some parts of the novel. Therefore, this novel, in spite of its low narrative speed, is full of motion, excitement, dynamism and movement, fright and apprehension, and internal and external conflicts. In other words, this novel has a low rhythm and fast dynamism. Hence, this study is an attempt to examine the strategies that the novelist has deployed to increase the motion and dynamism of the narration besides the narrative speed and the factors influencing on that.

Poetic inspiration is one of the major topics dealt with in literary criticism. The objective of this paper is to show the similarities between human birth and composition of poetry , which as Qabbani requires a lot of care to be taken so as to protect the child the against

The artistic works of the eminent and renowned artists in the past , reflects an image of their true disposition. Literary Works , Which arc the representations of those geal Moments of creativity can lead the wise reader to the inside world of their creators , though al limes , for different reasons some works are created which do not have much in common with their crators' real personality. these tricks however can be defected , through careful consideration. It is absolutely evident that you can express fair judgments over a writer's ideas if you have access to all his hiterary works. you can never rebuild a poet's mental fram work through briefly analysing only a part of his or her poems. More over , broad Knowledge and awareness , is the certain prcrcguisite for making fair judgments This article will auempt to analyse the judgments made about "SAAD!", the greut Iranian poet.

Background: A retrospective observational study was conducted at 3 health care organizations to identify clinical gaps in care for patients with stage 3 or 4 chronic kidney disease (CKD), and financial opportunity from U.S. risk adjustment payment systems. Lack of evaluation for CKD in patients with diabetes was also assessed., Methods: Outpatient longitudinal laboratory results and patient metadata available in the electronic medical record, laboratory information system, and/or laboratory billing or facility claims data for the calendar year 2021 were evaluated. Laboratory results were compared to billing data (ICD-10 codes) and risk adjustment scores including Hierarchical Condition Categories (HCC) to determine if laboratory-identified CKD was coded as a disease condition in the electronic medical record. Adults 18 to 75 years of age were included; inpatient laboratory results and pregnant individuals were excluded., Results: At the 3 institutions, 12,478 of 16,063 (78%), 487 of 1511 (32%) and 19,433 of 29,277 (66%) of patients with laboratory evidence of stage 3 or 4 CKD did not have a corresponding ICD-10 or HCC code for CKD in the electronic medical record. For patients at the 3 institutions with diabetes on the basis of an HbA1c value of ≥ 6.5%, 34,384 of 58,278 (59%), 2274 of 2740 (83%) and 40,378 of 52,440 (77%) had not undergone guideline-recommended laboratory testing for CKD during the same 12 months. Using publicly available data for calendar year 2021, an estimated 3246 of 32,398 patients (9.9%) at the 3 institutions with undocumented CKD stages 3-4 would be enrolled in Medicare Advantage or Affordable Care Act Marketplace programs. The imputed lost reimbursement under risk-adjusted payment systems for under-documentation of CKD in this subset of patients was $2.85 M for the three institutions combined, representing lost opportunity for both identification and proactive clinical management of these patients, and financial recovery for the costs of providing that care., Conclusions: Clinical laboratories can provide value beyond routine diagnostics, helping to close gaps in care for identification and management of CKD, stratifying subgroups of patients to identify risk, and capturing missed reimbursement through risk adjustment factors., Competing Interests: Declarations. Ethics approval and consent to participate: This is a retrospective observational study using existing data. There were no study interventions. The existing data were anonymized to protect privacy. The study received ethics approvals from the ethics committees of all three participating institutions: the Northwell Health Institutional Review Board; the University of Vermont Research Protections Office, and the Geisinger Health Institutional Review Board; The research was considered minimal risk because of the retrospective nature of the study and exempt from the need for informed consent (Northwell Health, Geisinger Health), or did not meet the regulatory definition of research under 45 CFR 46.102(d) and was classified as quality improvement (University of Vermont). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Synchronous colorectal carcinoma is having more than 1 primary carcinoma detected in a single patient at the same time or within 6 months of tumor diagnosis. Metachronous colorectal carcinoma is the presence of more than 1 primary carcinoma detected consecutively in a single person after a set time interval. Patients with Lynch syndrome and Muir-Torre syndrome (a subset of Lynch syndrome) inherit a germline mutation in 1 of the mismatch repair (MMR) genes. Patients with synchronous colorectal carcinoma have a higher proportion of MMR-mutated cancers than patients with solitary colorectal carcinoma. Most studies in the literature indicate that patients with synchronous colorectal cancers typically have only 2 carcinomas. However, there have been reports of a single patient having up to 6 synchronous carcinomas in the large intestine. This report discusses a patient with 9 simultaneous colorectal cancers at the initial diagnosis, along with a history of bladder cancer, sebaceous adenoma, and duodenal adenoma, associated with a germline mutS homolog 2 ( MSH2 ) mutation. Additionally, the report explores various aspects of having synchronous colorectal cancers. More studies are needed to clarify the clinicopathologic and molecular landscape of these rare tumors and identify the best management and treatment strategies for these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The feasibility of implementing genome sequencing as an adjunct to traditional newborn screening (NBS) in newborns of different racial and ethnic groups is not well understood., Objective: To report interim results of acceptability, feasibility, and outcomes of an ongoing genomic NBS study in a diverse population in New York City within the context of the New York State Department of Health Newborn Screening Program., Design, Setting, and Participants: The Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study was a multisite, single-group, prospective, observational investigation of supplemental newborn genome screening with a planned enrollment of 100 000 participants. Parent-reported race and ethnicity were recorded at the time of recruitment. Results of the first 4000 newborns enrolled in 6 New York City hospitals between September 2022 and July 2023 are reported here as part of a prespecified interim analysis., Exposure: Sequencing of 156 early-onset genetic conditions with established interventions selected by the investigators were screened in all participants and 99 neurodevelopmental disorders associated with seizures were optional., Main Outcomes and Measures: The primary outcome was screen-positive rate. Additional outcomes included enrollment rate and successful completion of sequencing., Results: Over 11 months, 5555 families were approached and 4000 (72.0%) consented to participate. Enrolled participants reflected a diverse group by parent-reported race (American Indian or Alaska Native, 0.5%; Asian, 16.5%; Black, 25.1%; Native Hawaiian or Other Pacific Islander, 0.1%; White, 44.7%; 2 or more races, 13.0%) and ethnicity (Hispanic, 44.0%; not Hispanic, 56.0%). The majority of families consented to screening of both groups of conditions (both groups, 90.6%; disorders with established interventions only, 9.4%). Testing was successfully completed for 99.6% of cases. The screen-positive rate was 3.7%, including treatable conditions that are not currently included in NBS., Conclusions and Relevance: These interim findings demonstrate the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in a population of different racial and ethnic groups. DNA sequencing offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots. Additional studies are required to understand if these findings are generalizable to populations of different racial and ethnic groups and whether introduction of sequencing leads to changes in management and improved health outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT05990179.

Context.—: In their 2014 article "New Immunohistochemistry for B-cell Lymphoma and Hodgkin Lymphoma," Zhang and Aguilera reviewed new immunohistochemical markers for B-cell lymphoma and Hodgkin lymphoma and described how to use these markers for correct lymphoma diagnoses, using the 2008 World Health Organization classifications. Recently, the World Health Organization's WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues published 2022 updates, and, in quick sequence, a second group published an alternative International Consensus Classification of myeloid neoplasms, acute leukemias, and mature lymphoid neoplasms. Regardless of the system a hematopathologist chooses to follow, updates in the immunohistochemical diagnosis of disease are described in both publications as well as in the primary literature. In addition to updated classifications, the increasing use of small biopsy samples for the evaluation of lymphadenopathy continues to challenge hematopathology diagnosis and increase the utilization of immunohistochemistry., Objective.—: To review new immunohistochemical markers or new uses of previously known immunohistochemical markers in the evaluation of hematolymphoid neoplasia for the practicing hematopathologist., Data Sources.—: Data were obtained from a literature review and personal practice experience., Conclusions.—: The practicing hematopathologist requires knowledge of the ever-expanding repertoire of immunohistochemistry for the diagnosis and treatment of hematolymphoid neoplasia. New markers presented in this article help to complete our understanding of disease, diagnosis, and management., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined., Methods: Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2- related neurodevelopmental disorder., Results: We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p.(Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain., Conclusion: We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management., Competing Interests: Competing interests: LF, KW, IMW, FZ, EAN and ET are employees of GeneDx. All other coauthors have no conflicts of interest related to the work in this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: SLC6A1 encodes GAT-1, a major gamma-aminobutyric acid (GABA) transporter in the brain. GAT-1 maintains neurotransmitter homeostasis by removing excess GABA from the synaptic cleft. Pathogenic variants in SLC6A1 disrupt the reuptake of GABA and are associated with a neurobehavioural phenotype., Methods: Medical history interviews, seizure surveys, Vineland Adaptive Behavior Scales Second Edition and other behavioural surveys were completed by primary care givers of 28 participants in Simons Searchlight. All participants underwent clinical whole exome sequencing or gene panel sequencing. Additional cases from the medical literature with comparable data were included., Results: We identified 28 individuals with largely de novo pathogenic/likely pathogenic variants including missense (15/21 or 71%) and truncating variants (6/21 or 29%). Missense variants were largely clustered around the sixth and seventh transmembrane domains, which functions as a GABA binding pocket. The phenotype of individuals with pathogenic variants in SLC6A1 includes hypotonia, intellectual disability/developmental delay, language disorder/speech delay, autism spectrum disorder, sleep issues and seizures., Conclusion: Pathogenic variants in SLC6A1 are associated with a clinical phenotype of developmental delay, behaviour problems and seizures. Understanding of the genotype-phenotype correlation within SLC6A1 may provide opportunities to develop new treatments for GABA-related conditions., Competing Interests: Competing interests: CT is an employee of Geisinger Health System. EB and LGS are employees of Simons Foundation Autism Research Initiative., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Homozygous pathogenic variants in WDR45B were first identified in six subjects from three unrelated families with global development delay, refractory seizures, spastic quadriplegia, and brain malformations. Since the initial report in 2018, no further cases have been described. In this report, we present 12 additional individuals from seven unrelated families and their clinical, radiological, and molecular findings. Six different variants in WDR45B were identified, five of which are novel. Microcephaly and global developmental delay were observed in all subjects, and seizures and spastic quadriplegia in most. Common findings on brain imaging include cerebral atrophy, ex vacuo ventricular dilatation, brainstem volume loss, and symmetric under-opercularization. El-Hattab-Alkuraya syndrome is associated with a consistent phenotype characterized by early onset cerebral atrophy resulting in microcephaly, developmental delay, spastic quadriplegia, and seizures. The phenotype appears to be more severe among individuals with loss-of-function variants whereas those with missense variants were less severely affected suggesting a potential genotype-phenotype correlation in this disorder. A brain imaging pattern emerges which is consistent among individuals with loss-of-function variants and could potentially alert the neuroradiologists or clinician to consider WDR45B-related El-Hattab-Alkuraya syndrome., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

The purpose of this study was to evaluate the clinical and genetic findings of 53-year-old monozygotic twins who had bilateral otosclerosis and right-sided superior semicircular canal near dehiscence (SSCND). Monozygotic twins at the age of 53 presented with conductive hearing loss and normal tympanic membranes. Detailed audiovestibular testing and computed tomography scan revealed that both patients had concurrent otosclerosis and SSCND. Conservative management (hearing aids) was the treatment for these patients. Exome sequencing (ES) for the twins and their affected mother identified a heterozygous missense variant in the EYA4 (c.1744G>A; p.Glu582Lys) gene. This is the first case report to present these separate entities identified in monozygotic twins with a heterozygous missense variant in the EYA4 gene. Our ES data may imply a possible causal relationship or association between variants in the EYA4 gene and concurrent otosclerosis and SSCND.

Autosomal recessive cerebellar ataxias (ARCA) are characterized by the abnormal structure of the cerebellum and spinal cord. Spinocerebellar ataxia type 18 (MIM 616204), one of the ARCA, is caused by the loss-of-function mutations of the GRID2 gene due to deletions. Missense mutations in the GRID2 cause ataxia with the gain-of-function mechanism. We report a homozygous GRID2  duplication in childhood-onset ataxia in two siblings. The clinical exome sequencing was performed on one of the siblings. No disease-causing mutations were reported as a result of the clinical exome test. Chromosomal microarray analysis was performed on the entire family using Affymetrix Optima ® chips. Chromosomal microarray analysis showed a ~ 121-kb homozygous duplication of GRID2 (arr[GRCh37]4q22.2(94426536_94613158) × 4), including exon 14, in both siblings. Previously, GRID2 has been associated with an autosomal recessive (loss-of-function) and autosomal semi-dominant (gain-of-function) forms of ataxia. To the best of our knowledge, this is the first study to identify a homozygous duplication of GRID2 causing loss of function of the GluRD2 protein. These findings provide us with the conclusion that copy number variation analyses should be in the diagnostic process of autosomal recessive ataxia types., (© 2020. Belgian Neurological Society.)

Purpose: To provide a detailed clinical and cytogenomic summary of individuals with chromosome 8p rearrangements of invdupdel(8p), del(8p), and dup(8p)., Methods: We enrolled 97 individuals with invdupdel(8p), del(8p), and dup(8p). Clinical and molecular data were collected to delineate and compare the clinical findings and rearrangement breakpoints. We included additional 5 individuals with dup(8p) from the literature for a total of 102 individuals., Results: Eighty-one individuals had recurrent rearrangements of invdupdel(8p) (n = 49), del(8p)_distal (n = 4), del(8p)_proximal (n = 9), del(8p)_proximal&distal (n = 12), and dup(8p)_proximal (n = 7). Twenty-one individuals had nonrecurrent rearrangements. While all individuals had neurodevelopmental features, the frequency and severity of clinical findings were higher in individuals with invdupdel(8p), and with larger duplications. All individuals with GATA4 deletion had structural congenital heart defects; however, the presence of structural heart defects in some individuals with normal GATA4 copy number suggests there are other potentially contributing gene(s) on 8p., Conclusion: Our study may inform families and health-care providers about the associated clinical findings and severity in individuals with chromosome 8p rearrangements, and guide researchers in investigating the underlying molecular and biological mechanisms by providing detailed clinical and cytogenomic information about individuals with distinct 8p rearrangements., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)