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The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S-SCAM, by employing multiple functional domains crucial for synaptic signaling and protein-protein interactions. Predominantly expressed in dendrites, CNKSR2 is vital for dendritic spine morphogenesis in hippocampal neurons. Its loss-of-function variants result in reduced PSD size and impaired hippocampal development, affecting processes including neuronal proliferation, migration, and synaptogenesis. We present 15 patients including three from the MENA (Middle East and North Africa), a region with no documented mutations in CNKSR2. Each individual displays unique clinical presentations that encompass developmental delay, ID, language/speech delay, epilepsy, and autism. Genetic analyses revealed 14 distinct variants in CNKSR2, comprising five nonsense, three frameshift, two splice, and four missense variants, of which 13 are novel. The ACMG guidelines unanimously interpreted these 14 variants in 15 individuals as pathogenic, highlighting the detrimental impact of these CNKSR2 genetic alterations and confirming the molecular diagnosis of MRXSHG. Importantly, variants Ser767Phe and Ala827Pro may lead to proteasomal degradation or reduced PSD size, contributing to the neurodevelopmental phenotype. Furthermore, these two amino acids, along with another two affected by four missense variants, exhibit complete conservation in nine vertebrate species, illuminating their crucial role in the gene's functionality. Our study revealed unique new digital and brain phenotype, including pointed fingertips (fetal pads of fingertips), syndactyly, tapering fingers, and hippocampal atrophy. These novel clinical features in MRXSHG, combined with 13 novel variants, expand the phenotypic and genotypic spectra of MRXSHG associated with CNKSR2 mutations., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Hereditary sensory and autonomic neuropathy type 9 (HSAN9) is a rare genetic disorder caused by genetic alterations in the TECPR2 locus and is characterized by developmental and intellectual disability, respiratory dysfunction, gastroesophageal reflux disease (GERD), and sensory and autonomic dysfunction, which are shared among the HSAN family., Methods: Whole-exome sequencing (WES) was performed on samples from both probands, and the relevant genetic variants were confirmed in their families using Sanger sequencing. Additionally, a comprehensive literature review was conducted on previously reported cases of HSAN9, and the clinical and genetic data were assessed to provide insight into the genetic and clinical characteristics of the disease., Results: We identified two new cases of HSAN9 with a shared novel variant of TECPR2 (NM_014844.5), c.1568del: p.Ser523PhefsTer12, classified as pathogenic according to ACMG guidelines. The probands showed characteristics of GERD, respiratory dysfunction, gait abnormalities, and developmental and speech delay, and both cases were deceased as a result of severe respiratory infection. The results of the literature review included 34 cases from 9 studies, revealing a wide range of genetic and clinical characteristics., Conclusions: Our study identified two new cases of HSAN9 with a novel variant in TECPR2, confirmed by WES. The clinical characteristics of the patients as well as the conduction of a comprehensive literature review are crucial in the early diagnosis and management of the disease and establishment of genotype-phenotype correlations., Competing Interests: Declarations. Ethics approval and consent to participate: This study is in accordance with the tenets of the Declaration of Helsinki and was approved by the Ethical Committee at the Shahid Beheshti University of Medical Sciences. Informed consent was obtained from adult participants to participate in the study. Written informed consent was obtained from parents of kin next of kin for all participants aged under 18. Consent for publication: Written informed consent for publication of identifying images or other personal or clinical details was obtained from the parents or legal guardians of any participant under the age of 18. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Over the past decade, substantial scientific evidence has showed that long non-coding RNAs (lncRNAs) are extensively expressed and play a crucial role in gene modulation through a diverse range of transcriptional, and post-transcriptional mechanisms. Recent discoveries have emphasized the involvement of lncRNAs in maintaining cellular homeostasis and neurogenesis in the brain. Accumulating reports identified dysregulated lncRNAs associated with psychiatric disorders, including autism. In this study, we examined the expression levels of DISC2, Linc00945, Foxg1-as1, Csnk1a1p, and Evf2 lncRNAs in blood samples from 21 clinically diagnosed autistic patients based on the Diagnostic and Statistical Manual of Mental Disorders criteria-5th edition (DSM-5), compared to age, sex, and ethnically-matched 25 healthy individuals. RNA extraction and cDNA synthesis were performed, followed by real-time PCR for quantification of lncRNAs expression levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate biomarker potential. Additionally, we investigated the correlation between gene expression levels and autism comorbidities. Our results showed a significant decrease in Csnk1a1p expression in patients with autism spectrum disorder (ASD) compared to healthy children (P value = 0.0008). ROC curve analysis indicated that Csnk1a1p expression levels could effectively discriminate patients from healthy controls (AUC = 0.837, P value = 0.000284). No significant differences were observed between Csnk1a1p expression levels and comorbidity with ADHD or intellectual disability (p-value > 0.05). Based on these findings, Csnk1a1p may play a significant role in autistic patients and could serve as a potential biomarker for diagnostic and predictive purposes, as well as a therapeutic target., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval The study protocol was approved by the ethical committee of Mashhad University of Medical Science. (IR.MUMS.MEDICAL.REC.1397.247). Consent to participate Written informed consent was obtained from the parents of participants.., (© 2024. The Author(s).)

Background: New York State implemented CFTR gene sequencing into the Cystic Fibrosis newborn screening (CF NBS) algorithm on 12/1/2017 to reduce false positive screens. With addition of sequencing, infants with 2 CFTR variants but low or intermediate sweat chloride levels classified as CFTR-related metabolic syndrome/CF screen-positive, inconclusive diagnosis (CRMS/CFSPID) are identified at a higher frequency, posing challenges to clinicians and families., Methods: Data from 375 screen-positive newborns between 12/1/2017 and 11/30/2020 were analyzed. We summarized 1-3 years of clinical follow-up for babies with CRMS/CFSPID following implementation of the IRT-DNA-SEQ algorithm., Results: Among 375 newborns referred, 223 (59.5 %) were classified as CRMS/CFSPID. Overall, 195/223 (87.4 %) had a CF-causing/pathogenic/likely pathogenic CFTR variant and a variant of varying clinical consequence (VCC) or uncertain significance (VUS). The most common VCC or VUS was 5T-12TG [n = 90/223 (40 %)]. All initial and repeat sweat chloride test (SCT) values for this cohort were <60 mmol/L after 1-3 years follow-up. Ninety-nine infants had ≥1 repeat SCT. Forty-two (18.8 %) had ≥1 SCT in the intermediate range (30-59 mmol/L) and 181 (81.2 %) were <30 mmol/L. Twenty-nine infants had sweat chloride increasing ≥5 mmol/L per year (29.3 % of infants with repeat testing). Fecal elastase was reported for 114/223 infants; none were abnormal. There were no conversions to CF during the 3-year follow-up period, however 2 infants have subsequently converted with diagnostic SCTs., Conclusions: The New York experience may help inform updates to clinical guidelines, which are needed to optimize care, management, counseling, and long-term follow-up of infants and children with CRMS/CFSPID., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: The article explores the potential risk of secondary cancer (SC) due to radiation therapy (RT) and highlights the necessity for new modeling techniques to mitigate this risk., Methods: By employing machine learning (ML) models, specifically decision trees, in the research process, a practical framework is established for forecasting the occurrence of SC using patient data., Results & Discussion: This framework aids in categorizing patients into high-risk or low-risk groups, thereby enabling personalized treatment plans and interventions. The paper also underscores the many factors that contribute to the likelihood of SC, such as radiation dosage, patient age, and genetic predisposition, while emphasizing the limitations of current models in encompassing all relevant parameters. These limitations arise from the non-linear dependencies between variables and the failure to consider factors such as genetics, hormones, lifestyle, radiation from secondary particles, and imaging dosage. To instruct and assess ML models for predicting the occurrence of SC based on patient data, the paper utilizes a dataset consisting of instances and attributes., Conclusion: The practical implications of this research lie in enhancing our understanding and prediction of SC following RT, facilitating personalized treatment approaches, and establishing a framework for leveraging patient data within the realm of ML models., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance., Competing Interests: Declaration of competing interest Dr. Guimbellot reports consulting fees from Vertex Pharmaceuticals Incorporated, outside the submitted work. All other authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Autosomal recessive genetic disorders pose significant health challenges in regions where consanguineous marriages are prevalent. The utilization of exome sequencing as a frequently employed methodology has enabled a clear delineation of diagnostic efficacy and mode of inheritance within multiplex consanguineous families. However, these aspects remain less elucidated within simplex families., Methods: In this study involving 12 unrelated simplex Iranian families presenting syndromic autism, we conducted singleton exome sequencing. The identified genetic variants were validated using Sanger sequencing, and for the missense variants in FOXG1 and DMD, 3D protein structure modeling was carried out to substantiate their pathogenicity. To examine the expression patterns of the candidate genes in the fetal brain, adult brain, and muscle, RT-qPCR was employed., Results: In four families, we detected an autosomal dominant gene (FOXG1), an autosomal recessive gene (CHKB), and two X-linked autism genes (IQSEC2 and DMD), indicating diverse inheritance patterns. In the remaining eight families, we were unable to identify any disease-associated genes. As a result, our variant detection rate stood at 33.3% (4/12), surpassing rates reported in similar studies of smaller cohorts. Among the four newly identified coding variants, three are de novo (heterozygous variant p.Trp546Ter in IQSEC2, heterozygous variant p.Ala188Glu in FOXG1, and hemizygous variant p.Leu211Met in DMD), while the homozygous variant p.Glu128Ter in CHKB was inherited from both healthy heterozygous parents. 3D protein structure modeling was carried out for the missense variants in FOXG1 and DMD, which predicted steric hindrance and spatial inhibition, respectively, supporting the pathogenicity of these human mutants. Additionally, the nonsense variant in CHKB is anticipated to influence its dimerization - crucial for choline kinase function - and the nonsense variant in IQSEC2 is predicted to eliminate three functional domains. Consequently, these distinct variants found in four unrelated individuals with autism are likely indicative of loss-of-function mutations., Conclusions: In our two syndromic autism families, we discovered variants in two muscular dystrophy genes, DMD and CHKB. Given that DMD and CHKB are recognized for their participation in the non-cognitive manifestations of muscular dystrophy, it indicates that some genes transcend the boundary of apparently unrelated clinical categories, thereby establishing a novel connection between ASD and muscular dystrophy. Our findings also shed light on the complex inheritance patterns observed in Iranian consanguineous simplex families and emphasize the connection between autism spectrum disorder and muscular dystrophy. This underscores a likely genetic convergence between neurodevelopmental and neuromuscular disorders., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The ultra-rare autosomal recessive genetic disorder, You-Hoover-Fong Syndrome (YHFS), is caused by defects in the TELO2 gene and is characterized by intellectual disability, developmental delay, and ocular impairments. This study aims to contribute to a better understanding of YHFS by reviewing previous cases and introducing a novel variant in a new case., Methods: Whole exome sequencing (WES) was conducted on the proband to identify genetic variants, and Sanger sequencing was used to confirm variants within the family. This article presents a comprehensive collection of reported cases of YHFS, incorporating both molecular and clinical data, through an extensive literature search and analysis of English-language studies published until June 2023., Results: Using WES, a novel homozygous missense variant, c.1799A > G (p. Tyr600Cys), was identified in the TELO2 gene in a 4-year-old Iranian male patient. Novel clinical features, including choanal atresia and clubfoot, were also identified. A comprehensive literature review identified 27 patients with YHFS, with 20 variants in the TELO2 gene. Missense pathogenic variants were the most common type of pathogenic variant, and the most common features were microcephaly and intellectual impairment., Conclusion: This study presents the first case of pathogenic variants in TELO2 gene in Iran, expands the genotypic and phenotypic spectrum of YHFS and contributes to the growing body of literature pertaining to YHFS. Furthermore, our findings highlight the importance of genetic testing for non-consanguineous carrier screening, as compound heterozygosity may be a significant factor in the development of YHFS. Further research is needed to clarify the molecular mechanisms underlying YHFS pathogenesis., (© 2024. Fondazione Società Italiana di Neurologia.)

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by muscle stiffness (myotonia) and chondrodysplasia. This disease is caused by biallelic loss of function mutations in the HSPG2 gene, which encodes the core protein of perlecan. This study aims to investigate causative variants in two sisters born to consanguineous Iranian parents. Both patients were presented with myotonia and a mask-like face; moreover, they showed a less common symptom, gastrointestinal bleeding, which is not typical of SJS and has only been reported in one patient. Regarding the crucial role of perlecan in vascular structure and mucosal stability, bleeding disorders could be expected in perlecan dysfunctions. In addition to the case study, a comprehensive literature review was conducted to gather information on similar genetic variants, associated clinical features, and possible disease mechanisms. Results of this study contribute to our understanding of the genetic and clinical aspects of Schwartz-Jampel syndrome, and more importantly, the manifestation of gastrointestinal bleeding in patients with Schwartz-Jampel syndrome., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Background: New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs)., Aims: As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers., Results: Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor., Conclusion: Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results., (© 2024 Wiley Periodicals LLC.)

Aim: The purpose of this study is to evaluate the oral probiotic effect on pregnancy outcomes in pregnant women undergoing cerclage compared to placebo., Methods: This study was a double-blind randomized clinical trial undertaken in Yasuj, Iran. 114 eligible participants who have undergone cerclage were randomly divided to either receive probiotic adjuvant or 17α-OHP (250 mg, IM) with placebo from the 16th -37th week of pregnancy by "block" randomization method. Our primary outcomes were preterm labor (PTB) (late and early) and secondary outcomes were other obstetrical and neonatal outcomes included preterm pre-labor rupture of membranes (PPROM), pre-labor rupture of membranes (PROM), mode of delivery, and neonatal outcomes including anthropometric characterize and Apgar score (one and fifth-minute)., Results: Results show that there are no statistically significant differences between the two groups in terms of PTB in < 34th (15.51% vs. 17.86%; P = 0.73) and 34-37th weeks of pregnancy (8.7% vs. 16.1%; P = 0.22), and mode of delivery (P = 0.09). PPROM (8.7% vs. 28.5%; P = 0.006) PROM (10.3% vs. 25%; P = 0.04) was significantly lower in patients receiving probiotic adjuvant compared to the control group. After delivery, the findings of the present study showed that there were no significant differences in newborn's weight (3082.46 ± 521.8vs. 2983.89 ± 623.89), head circumstance (36.86 ± 1.53vs. 36.574 ± 1.52), height (45.4 ± 5.34 vs. 47.33 ± 4.92) and Apgar score in one (0.89 ± 0.03 vs. 0.88 ± 0.05) and five minutes (0.99 ± 0.03vs. 0.99 ± 0.03) after birth., Conclusion: Our result has shown that the consumption of Lactofem probiotic from the 16th week until 37th of pregnancy can lead to a reduction of complications such as PPROM and PROM., (© 2024. The Author(s).)

Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2. Most types of GSDs observed in the cohort were associated with hepatomegaly, which was the most common clinical presentation. This study provides valuable insights into the phenotype and genotype spectrum of GSDs in a cohort of Iranian patients. The identification of novel variants adds to the growing body of knowledge regarding the genetic landscape of GSDs and has implications for genetic counseling and future therapeutic interventions. The diverse nature of GSDs underscores the need for comprehensive genetic testing methods to improve diagnostic accuracy. Continued research in this field will enhance our understanding of GSDs, ultimately leading to improved management and outcomes for individuals affected by these rare metabolic disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders., Material and Methods: The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative., Results: The first patient exhibited a homozygous mutation in the TPK1 gene, NM&#95;022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM&#95;025243.4:c.1385dupA:pY462X, within the SLC19A3 gene., Conclusions: Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD., Competing Interests: The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication., (© 2024 The Authors.)

Background: Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH., Methods: Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH., Results: This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9., Conclusions: This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH., (© 2024. The Author(s).)

Objective: To identify predictors of change in lung function and body weight during health care transition in cystic fibrosis (CF)., Methods: We conducted a retrospective cohort study using data from the CF Foundation Patient Registry and the web-based transition program CF RISE (Responsibility. Independence. Self-care. Education) for patients aged 16-25 years who transitioned to adult care from 2013 through 2019. We modeled change in forced expiratory volume in 1 second % predicted and weight using linear regression fit with generalized estimating equations. Predictors included gap in care (time between last pediatric and first adult outpatient visit), transition program engagement, and sociodemographic and medical factors., Results: Among 12 420 adolescents and young adults (AYAs), 3876 transitioned to adult care with a median gap in care of 7.6 months. Patients from CF centers with greater rates of CF RISE engagement had improved lung function and weight at their first adult outpatient visit. Coverage on a parent's insurance plan and absence of CF complications predicted increased lung function. History of a nonlung transplant and sinus disease predicted increased weight. Comorbid diabetes mellitus and gaps in care >3 months predicted decreased lung function with longer gaps in care associated with greater decrease. A gap in care of 6-9 months predicted decreased weight. Control variables including baseline forced expiratory volume in 1 second and weight, and exacerbation status were also statistically significant., Conclusions: Findings suggest 2 promising targets to improve transition of AYAs with CF: increasing AYA engagement in CF RISE and reducing gaps in care during the transition period., Competing Interests: Declaration of Competing Interest All phases of this study were supported by a National Institute of Nursing Research (NINR) grant, 1F31NR020141-01. K.M. also was supported by Agency for Healthcare Research and Quality (AHRQ) grant number T32HS000063 as part of the Harvard-wide Pediatric Health Services Research Fellowship Program. The NINR and AHRQ had no role in the design and conduct of the study. The first draft of the manuscript was written by K.M.; no honorarium or other compensation was received. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder characterized by a range of physical, cognitive, and behavioral abnormalities. This study aimed to perform a comprehensive review of the literature on CdLS and investigate two cases of CdLS with distinct phenotypes that underwent WES to aid in their diagnosis., Methods: We conducted a comprehensive review of the literature on CdLS along with performing whole-exome sequencing on two CdLS patients with distinct phenotypes, followed by Sanger sequencing validation and in-silico analysis., Results: The first case exhibited a classic CdLS phenotype, but the initial WES analysis of blood-derived DNA failed to identify any mutations in CdLS-related genes. However, a subsequent WES analysis of skin-derived DNA revealed a novel heterozygous mutation in the NIPBL gene (NM&#95;133433.4:c.6534&#95;6535del, p.Met2178Ilefs*8). The second case was presented with a non-classic CdLS phenotype, and WES analysis of blood-derived DNA identified a heterozygous missense variant in the SMC1A gene (NM&#95;006306.4:c.2320G>A, p.Asp774Asn)., Conclusions: The study shows the importance of considering mosaicism in classic CdLS cases and the value of WES for identifying genetic defects. These findings contribute to our understanding of CdLS genetics and underscore the need for comprehensive genetic testing to enhance the diagnosis and management of CdLS patients., (© 2024. The Author(s).)

This review article presents an in-depth analysis of the current state of research on receptor tyrosine kinase regulatory non-coding RNAs (RTK-RNAs) in solid tumors. RTK-RNAs belong to a class of non-coding RNAs (nc-RNAs) responsible for regulating the expression and activity of receptor tyrosine kinases (RTKs), which play a critical role in cancer development and progression. The article explores the molecular mechanisms through which RTK-RNAs modulate RTK signaling pathways and highlights recent advancements in the field. This include the identification of potential new RTK-RNAs and development of therapeutic strategies targeting RTK-RNAs. While the review discusses promising results from a variety of studies, encompassing in vitro, in vivo, and clinical investigations, it is important to acknowledge the challenges and limitations associated with targeting RTK-RNAs for therapeutic applications. Further studies involving various cancer cell lines, animal models, and ultimately, patients are necessary to validate the efficacy of targeting RTK-RNAs. The specificity of ncRNAs in targeting cellular pathways grants them tremendous potential, but careful consideration is required to minimize off-target effects, the article additionally discusses the potential clinical applications of RTK-RNAs as biomarkers for cancer diagnosis, prognosis, and treatment. In essence, by providing a comprehensive overview of the current understanding of RTK-RNAs in solid tumors, this review emphasizes their potential as therapeutic targets for cancer while acknowledging the associated challenges and limitations., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Asthma is a common chronic disease characterized by inflammation of the airways. One of the most devastating consequences of this inflammatory process is the production of reactive oxygen species responsible for oxidative stress. Nasturtium officinale commonly known as watercress has traditionally been applied in Iranian folk medicine to treat respiratory disorders and diseases mainly bronchitis and asthma. In accordance with these ethnopharmacological reports, through our previous in vivo experiment, we have confirmed significant effect of its hydroalcoholic extract in reducing lung inflammation and oxidative stress in an ovalbumin-induced asthmatic rat model., Aim of the Study: The aim of the present study was to investigate the anti-inflammatory and antioxidant effects of N. officinale hydroalcoholic extract (NOE) in patients with asthma, in order to confirm our findings of the previous performed in vivo study., Material and Methods: The NOE capsules (500 mg) were treated twice daily for 4 weeks as a supplementary treatment in a randomized, double-blind, and placebo-controlled trial in asthmatics. The primary outcome was Asthma Control Test score. The blood samples were taken at the beginning and end of the study. Then, the level of inflammatory markers, oxidative stress markers and antioxidant enzyme activity were measured., Results: Treatment with NOE for one month caused a reduction in the levels of MDA, PCO and NO metabolite markers compared to the placebo group. In addition, FRAP levels as an indicator of total antioxidant capacity in the intervention group was significantly increased at the end of the treatment period compared to pre-treatment values., Conclusion: Findings demonstrated that NOE may have a therapeutic effect on asthma by improving oxidative stress. However, more studies are required to support these results. Moreover, bio-assay guided fractionation and isolation approach can be conducted to identify major bioactive compound/s., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: We aim to investigate the relationship between hsa&#95;circ&#95;0009361 plus hsa&#95;circ&#95;0009362 expression levels and the clinicopathological features of colorectal cancer (CRC) patients., Background: Circular RNAs (circRNAs) are implicated in the progression and development of CRC. CircRNAs have been recognized as diagnostic and prognostic biomarkers, opening up a new window to comprehend the molecular basis of CRC. Given the significance of circRNAs and the G protein subunit b1 ( GNB1 ) gene in malignancies, the goal of the current investigation was to determine the expression levels of GNB1 derivative circular RNAs circGNB1 ( hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 ) in CRC and adjacent control tissues., Methods: The expression levels of the GNB1 derivative circular RNAs ( hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 ) were evaluated using the quantitative real-time PCR (qRT-PCR) method in 45 CRC tissues and adjacent control tissues. Furthermore, we analyzed the diagnostic power of the mentioned circRNAs by plotting the receiver operating characteristic (ROC) curve. The association between the expression levels of hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 was evaluated using correlation analysis., Results: Our results revealed that the expression levels of hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 were significantly down-regulated in CRC tissues compared to the adjacent control group. Analysis of patients' clinicopathological features indicated that expressions of hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 were differently related to lymph vascular invasion (P<0.001). ROC curve results showed that these circRNAs are good candidate diagnostic biomarkers in CRCs. Pearson's correlation test revealed a positive correlation between hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 expression levels (P<0.0001)., Conclusion: These results demonstrated that hsa&#95;circ&#95;0009361 and hsa&#95;circ&#95;0009362 expression levels may be used as possible diagnostic biomarkers for CRC., Competing Interests: The authors declare no conflict of interest., (© 2024, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

Background: Approximately 5% of colorectal cancers (CRCs) are hereditary. Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of recognized hereditary CRC. Although Iran, as a developing country, has a high incidence of CRC, the spectrum of variants has yet to be thoroughly investigated., Aims: This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS)., Methods and Results: In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features., Conclusion: Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS., (© 2023 Shahid Beheshti University of Medical Sciences. Cancer Reports published by Wiley Periodicals LLC.)

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity., Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg)., Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly ( P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT 2 ) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect., Conclusions: NO/cGMP/K ATP , 5HT 3 and D 2 pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

Aberrant activation of Wnt pathway is linked to dysregulation of several genes. DACT1 and DACT2 are members of the DACT family that participate in antagonizing of the Wnt signaling cascade. Thus in this study, we assessed the mRNA levels of DACT1 , DACT2 , and CYCLIN D1 in 70 pairs of CRC tissues compared to the adjacent tissues. Determination of the mRNA levels of DACT1 , DACT2 , and CYCLIN D1 was done by Quantitative Real-Time PCR (qRT-PCR). The correlation between DACT1 , DACT2 , and CYCLIN D1 genes was also examined. Receiver operating characteristic (ROC) curves was plotted to assess the diagnostic power. The association between histopathological parameters and the DACT1 , DACT2 , and CYCLIN D1 genes was investigated. The expression levels of DACT1 and CYCLIN D1 were remarkably higher in CRC tissues compared to the adjacent tissues ( p  < 0.0001). However, the expression of DACT2 was decreased ( p  < 0.001). Our results showed a significant correlation between the expression of DACT1 and CYCLIN D1 ( p  < 0.0001). DACT1 (AUC = 0.74, p  < 0.0001), DACT2 (AUC = 0.69, p  < 0.0003), and CYCLIN D1 (AUC = 0.75, p  < 0.0001) had good effectiveness in separation between CRC samples and adjacent tissues. We found a significant association between DACT1 expression with tumor site ( p  < 0.01). Also, a significant association was detected between DACT2 and CYCLIN D1 with tumor stage ( p < 0.005 and p  < 0.038, respectively). The findings suggested that DACT1 could function as an oncogene, whereas DACT2 was downregulated and can be considered as a tumor suppressor in CRC.

Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal cancer syndrome that is characterized by the development of multiple adenomas in the colon and rectum with high penetrance rates. This disease has specific features like the occurrence of pathogenic variations in the APC gene and diverse FAP phenotypes due to the occurrence region. In this study we aimed to evaluate pathogenic variants in exons of the APC gene in Iranian patients with FAP. A total of 35 FAP individuals were referred to the gastroenterology ward of Taleghani Hospital. As the aim of the study was to study the germline variations in the participants, the peripheral blood was collected and after the DNA extraction, PCR, and Sanger sequencing processes for the APC gene, the results were evaluated by the ACMG classification guidelines to report their pathogenicity. Accordingly, out of eight specific detected variants, three of them were novel, and the rest were reported previously. These eight variants were all truncating protein and pathogenic, and they were limited to 849-1378 codons. Overall, detected variants revealed discrepancies and parallels with previous reported cases in terms of quantity, occurrence region, and association with demographic and clinicopathological characteristics of patients. The spectrum of detected variants and the patient's phenotype showed distinct characteristics, such as occurrence in specific regions and the absence of extracolonic symptoms like Congenital hypertrophy of the retinal pigment epithelium (CHRPE). These findings open the path to comprehending the typical symptoms, their rarity, and their occurrence in the Iranian population and also due to the facts, we found that the studying of the APC gene alone for diagnosing FAP disease is not sufficient, and considering other genes are completely rational in the case of sequencing and studying the variants.

Introduction: Cystic fibrosis (CF) is a systemic autosomal recessive condition characterised by progressive lung disease. CF pulmonary exacerbations (PEx) are episodes of worsening respiratory status, and frequent PEx are a risk factor for accelerated lung function decline, yet many people with CF (PwCF) go untreated at the time of decline. The goal of this quality improvement (QI) initiative was to improve recognition, treatment and follow-up of PEx in PwCF., Methods: Using the Model for Improvement, the Cystic Fibrosis Learning Network (CFLN) initiated a QI innovation laboratory (iLab) with a global aim to decrease the rate of lung function decline in PwCF. The iLab standardised definitions for signals of PEx using a threshold for decline in forced expiratory volume in one second (FEV 1 ) and/or changes in symptoms. The FEV 1 decline signal was termed FIES (FEV 1 -indicated exacerbation signal). Processes for screening and recognition of FIES and/or symptom changes, a treatment algorithm and follow-up in the presence of a signal were tested concurrently in multiple settings., Specific Aims: The specific aim is to increase the per cent of PwCF assessed for a PEx signal at ambulatory encounters and to increase the per cent of recommendations to follow-up within 6 weeks for PwCF experiencing a PEx signal., Results: FIES recognition increased from 18.6% to 73.4% across all teams during the iLab, and every team showed an improvement. Of PwCF assessed, 15.8% experienced an FIES event (>10% decline in FEV 1 per cent predicted (FEV 1 pp)). Follow-up within 6 weeks was recommended for an average of 70.5% of those assessed for FIES and had an FEV 1 pp decline greater than 5%., Conclusion: The CFLN iLab successfully defined and implemented a process to recognise and follow-up PEx signals. This process has the potential to be spread to the larger CF community. Further studies are needed to assess the impact of these processes on PwCF outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1) is caused by biallelic mutations in the NALCN gene, the major ion channel responsible for the background Na + conduction in neurons. Through whole-exome sequencing (WES), we report three novel homozygous variants in three families, including c.1434 + 1G > A, c.3269G > A, and c.2648G > T, which are confirmed and segregated by Sanger sequencing. Consequently, intron 12's highly conserved splice donor location is disrupted by the pathogenic c.1434 + 1G > A variation, most likely causing the protein to degrade through nonsense-mediated decay (NMD). Subsequently, a premature stop codon is thus generated at amino acid 1090 of the protein as a result of the pathogenic c.3269G > A; p.W1090* variation, resulting in NMD or truncated protein production. Lastly, the missense mutation c.2648G > T; p.G883V can play a critical role in the interplay of functional domains. This study introduces recurrent urinary tract infections for the first time, broadening the phenotypic range of IHPRF1 syndrome in addition to the genotypic spectrum. This trait may result from insufficient bladder emptying, which may be related to the NALCN channelosome's function in background Na + conduction. This work advances knowledge about the molecular genetic underpinnings of IHPRF1 and introduces a novel phenotype through the widespread use of whole exome sequencing., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Preeclampsia (PE) is one of the leading disorders in pregnant women with maternal and fetal complications. Obesity is considered an important risk factor for the development of PE. Genetic variations in fat mass and obesity associated (FTO) gene may play a role in the development of PE. This study aimed to investigate the possible association between FTO gene rs9939609 and PE risk in a sample of Iranian pregnant women., Material and Methods: In this case-control study, 312 pregnant women were included, including 128 with PE and 184 without PE. Demographic data and blood samples were obtained from all individuals. The genotyping of rs9939609 polymorphisms was performed by the tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR) method, and the results of TP-ARMS-PCR were confirmed using DNA sequencing., Results: The genotype frequency was 50%, 47.7%, and 2.3% in pregnant patients and 37%, 47.8%, and 15.2% in healthy controls for TT, AT, and AA, respectively. The risk of PE was significantly reduced in the pregnant women having the AA genotype., Conclusion: Based on the results of the present study, rs9939609 polymorphism in the FTO gene may play a protective role against PE. However, further studies are warranted. [Figure: see text].

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is a rare autosomal dominant genetic disorder caused by genetic alterations in the CTNNB1 gene. CTNNB1 is a gene that encodes β-catenin, an effector protein in the canonical Wnt pathway involved in stem cell differentiation and proliferation, synaptogenesis, and a wide range of essential cellular mechanisms. Mutations in this gene are also found in specific malignancies as well as exudative vitreoretinopathy. To date, only a limited number of cases of this disease have been reported, and though they share some phenotypic manifestations such as intellectual disability, developmental delay, microcephaly, behavioral abnormalities, and dystonia, the variety of phenotypic traits of these patients shows extreme heterogeneity. In this study, two cases of NEDSDV with de novo CTNNB1 mutations: c.1420C>T(p.R474X) and c.1377&#95;1378Del(p.Ala460Serfs*29), found with whole exome sequencing (WES) have been reported and the clinical and paraclinical characteristics of these patients have been described. Due to such a wide range of clinical characteristics, the identification of new patients and novel variants is of great importance in order to establish a more complete phenotypic spectrum, as well as to conclude the genotype-phenotype correlations in these cases., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion., Research Question: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF?, Study Design and Methods: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both. Three categories of composite secondary outcomes were identified: difficult line placement, local soft tissue or skin reactions, and catheter malfunction. Data specific to the participant, catheter placement, and catheter management were collected in a centralized database. Risk factors for primary and secondary outcomes were analyzed by multivariate logistic regression., Results: Between June 2018 and July 2021, 157 adults and 103 children older than 6 years with CF had 375 PICCs placed. Patients underwent 4,828 catheter-days of observation. Of the 375 PICCs, 334 (89%) were ≤ 4.5 F, 342 (91%) were single lumen, and 366 (98%) were placed using ultrasound guidance. The primary outcome occurred in 15 PICCs for an event rate of 3.11 per 1,000 catheter-days. No cases of catheter-related bloodstream infection occurred. Other secondary outcomes developed in 147 of 375 catheters (39%). Despite evidence of practice variation, no risk factors for the primary outcome and few risk factors for secondary outcomes were identified., Interpretation: This study affirmed the safety of contemporary approaches to inserting and using PICCs in people with CF. Given the low rate of complications in this study, observations may reflect a widespread shift to selecting smaller-diameter PICCs and using ultrasound to guide their placement., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Pulmonary fibrosis (PF) is a chronic and progressive respiratory disease representing the final stage of lung inflammatory disorders. Reactive oxygen species (ROS), an essential factor in the formation and progression of pulmonary fibrosis, are a significant adverse effect of Bleomycin (BLM). Antioxidant activities have been found in Daphne oleoides . In this study, we attempted to explore the function of hydroalcoholic extract of Daphne oleoides ( D. oleoides ) and Betulin in inhibiting bleomycin (BLM)-induced pulmonary fibrosis in rat"., Materials and Methods: The current experimental study used 36 male Wistar rats (180-220). Following a random process, the animals were divided into six groups six (n = 6). Group, I (the control group) received normal saline, while Group II (the hazardous group) received intratracheal BLM (7.5 units per kg). Following the administration of BLM, Groups V and VI received daily doses of vitamin E (500 mg/kg/d, p.o.) and Betulin (10 mg kg/d, p.o.), whereas Groups III and IV received daily doses of Daphne oleoides extract (300 and 600 mg/kg/d, p.o.). Then, blood samples from the hearts of the animals were taken to assess the plasma concentrations of nitric oxide (NO) and malondialdehyde (MDA). Finally, the rats were euthanized, and the lung tissues were taken out for histological analysis and assessments of the levels of lung hydroxyproline (HP), ferric-reducing ability (FRAP), NO, Glutathione Concentration (GSH), thiol content (tSH) and MDA., Findings: Elevated lung index, lung hydroxyproline, NO, and MDA plasma levels, and a reduction in total body thiol content (tSH) in the group receiving BLM were evidence of pulmonary toxicity. Treatment with D. oleoides extracts, Betulin, and Vit E, especially at 600 mg/kg, led to a marked reduction in the above parameters compared with the BLM-received group (p < 0.01). Histological Analysis of the BLM-treated group showed a considerable Lung injury with interstitial infiltration, collapsed alveolar spaces, and alveolar septal thickening. These changes were mitigated with D. oleoides 600, Betulin-, and vitamin E. These changes were mitigated with D. oleoides 600, Betulin-, and vitamin E., Conclusion: These findings suggest that D. oleoides and Betulin prevent bleomycin-induced lung fibrosis in rats by decreasing inflammatory and antioxidant markers. Daphne oleoides , therefore, have the potential to be used therapeutically to treat pulmonary fibrosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: Adolescents with cystic fibrosis (CF) and their parents must navigate changing roles and responsibilities within the family including transfer of disease management responsibilities., Aim/objective: The aim of this qualitative study was to explore how families share and transfer CF management responsibility from the perspectives of adolescents with CF and their parents., Methods: Guided by qualitative descriptive methodology, we purposively sampled adolescent/parent dyads. Participants completed two surveys measuring family responsibility (Family Responsibility Questionnaire [FRQ]) and transition readiness (Transition Readiness Assessment Questionnaire [TRAQ]) We conducted semistructured video or phone interviews, used a codebook to guide team coding and analyzed qualitative data using both content analysis and dyadic interview analysis., Results: Thirty participants (15 dyads) enrolled (7% Black; 33% Latina/o; 40% female; adolescent age 14.4 ± 2 years; 66% prescribed highly effective modulator therapy; 80% of parents were mothers). Parent FRQ and TRAQ scores were significantly higher than their adolescent indicating differing perceptions of responsibility and transition readiness. We inductively identified four themes: (1) CF management is a delicate balance (CF management is a routine which is easily disrupted), (2) Growing up and parenting under extraordinary circumstances (the burden of CF weighs on families as they navigate adolescence), (3) Differing Perceptions of risk and responsibility (adolescent and parent perceptions of treatment responsibility and the risks of nonadherence do not always align), and (4) Balancing independence and protection (families must weigh the benefits and risks of allowing adolescents increased independence)., Conclusions: Adolescents and parents demonstrated differing perceptions of CF management responsibility, which may be related to a lack of communication between family members about this topic. To help facilitate alignment of parent and adolescent expectations, discussion of family roles and responsibility for CF management should begin early during the transition process and be discussed regularly during clinic visits., (© 2023 Wiley Periodicals LLC.)

The mTOR complex 1 (mTORC1) coordinates several important environmental and intracellular cues to control a variety of biological processes, such as cell growth, survival, autophagy, and metabolism, in response to energy levels, growth signals, and nutrients. The endoplasmic reticulum (ER) is a crucial intracellular organelle that is essential for numerous cellular functions, including the synthesis, folding, and modification of newly synthesized proteins, stress responsiveness, and maintainence of cellular homeostasis. mTOR-mediated upregulation of protein synthesis induces the accumulation of misfolded or unfolded proteins in the ER lumen, which induces ER stress, leading to activation of the unfolded protein response (UPR) pathway. Reciprocally, ER stress regulates the PI3K/AKT/mTOR signaling pathway. Therefore, under pathologic conditions, the cross-talk between the mTOR and UPR signaling pathways during cellular stress can critically affect cancer cell fate and may be involved in the pathogenesis and therapeutic outcome of cancer. Here, we discuss accumulating evidence showing the mechanism of action, interconnections, and molecular links between mTOR signaling and ER stress in tumorigenesis and highlights potential therapeutic implications for numerous cancers., (©2023 American Association for Cancer Research.)

Capparis spinosa L. (caper) is a halophytic plant that grows in semi-arid or arid environments. The current study used an integrated experimental and computational approach to investigate the network of inter-correlated effective variables on the activity of antioxidant enzymes, proline, and photosynthetic pigments in stressed caper. To investigate the possible relationships among intercorrelated variables and understand the possible mechanisms, predictive regression modelling, principal component analysis (PCA), Pearson's correlation, and path analysis were implemented. PCA successfully discerned different salt ratio- and drought-specific effects in data in the current study, and treatments with higher growth indices are easily recognizable. Different salt ratios did not have a significant effect on the activity of four antioxidant enzymes, proline and photosynthesis pigments content of caper. While at the mean level, the activity of four antioxidant enzymes of SOD, POD, CAT, and APX significantly increased under drought stress by 54.0%, 71.2%, 79.4%, and 117.6%, respectively, compared to 100% FC. The drought stress also significantly increased the content of carotemoid (29.3%) and proline (by 117.7%). Predictive equation models with highly significant R 2 were developed for the estimation of antioxidant enzyme activity and proline content (> 0.94) as well as pigments (> 0.58) were developed. Path analysis studies revealed that proline is the most important regressor in four antioxidant enzyme activities, while leaf tissue density was the most effective variable in the case of chlorophylls. Furthermore, the network of intercorrelated variables demonstrated a close relationship between caper's antioxidant defence system, pigments, and morphological parameters under stress conditions. The findings of this study will be a useful guide to caper producers as well as plant ecophysiological researchers., (© 2023. The Author(s).)

Background: FTO gene is associated with obesity, dietary intake, and the risk of colorectal cancer (CRC). In this study, patients with colorectal cancer were assessed for the interactions between FTO gene polymorphisms and dietary intake., Methods: This case-control study was carried out on 450 participants aged 35-70 years including 150 patients with colorectal cancer and 300 healthy controls. Blood samples were collected in order to extract DNA and genotyping of FTO gene for rs9939609 polymorphism. A validated 168-item food frequency questionnaire (FFQ) and the Nutritionist-IV software were used to assess dietary intake., Results: In the participants with the TT genotype of FTO rs9939609 polymorphism, CRC risk was significantly associated with higher intake of dietary fat (OR:1.87 CI95%:1.76-1.99, p = 0.04), vitamin B3 (OR:1.20 CI95%:1.08-1.65, p = 0.04), and vitamin C (OR:1.06 CI95%:1.03-1.15, p = 0.04) and lower intake of β-carotene (OR:0.98 CI95%:0.97-0.99, p = 0.03), vitamin E (OR:0.77 CI95%:0.62-0.95, p = 0.02), vitamin B1 (OR:0.15 CI95%:0.04-0.50, p < 0.01), and biotin (OR:0.72 CI95%:0.0.57-0.92, p = 0.01). No significant association was found between CRC and dietary intake in carriers of AA/AT genotypes after adjustments for the confounders., Conclusion: CRC risk may be decreased by β-carotene, vitamins E, B1, and biotin only in those without the risk allele of the FTO gene. The association of CRC and diet may be influenced by FTO genotype. Further studies are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gholamalizadeh, Jonoush, Mobarakeh, Amjadi, Alami, Valisoltani, Askarpour, Azizi-Tabesh, Mohammadian, Akbari, Rajabibazl, Alemrajabi, Poodineh, Sadeghi, Hosseinzadeh, Dahka, Badeli, Jarrahi and Doaei.)

Vanishing bile duct syndrome (VBDS) has been postulated that may be related to Hodgkin's lymphoma (HL). In the present study, we present a 75-year-old male patient with HL who received chemotherapy but has not received any radiotherapy. The patient's condition worsened in further days, and he died with the diagnosis of cirrhosis and hepatic failure., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Despite the fact that numerous studies have investigated the association between genetic polymorphisms and colorectal cancer (CRC), more research is required to comprehend the molecular mechanisms of CRC. In the present study, we investigated the association between lncRNA HOTAIR rs2366152 and rs1899663 polymorphisms with CRC susceptibility in the Iranian population., Methods: This case-control study consisting of 187 CRC patients and 200 healthy samples. The tetra-amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) technique was used for the genotyping of rs2366152 and rs1899663 polymorphisms., Results: The findings showed that the AG genotype of the rs2366152 polymorphism has a protective effect on CRC susceptibility (OR = 0.60, 95% CI: 0.38-0.94, p-value = 0.023). Furthermore, rs2366152 polymorphism associated with CRC risk in an over dominant inheritance model (p-value = 0.0089). According to the outcomes of the rs1899663 polymorphism, the GT genotype had protective effects on CRC risk (OR = 0.55, 95% CI: 0.35-0.86, p-value = 0.008). Moreover, statistical analysis has shown that the rs1899663 polymorphism was associated with CRC risk in dominant (p-value = 0.013) and overdominant (p-value = 0.0086) inheritance models in the Iranian population., Conclusion: This study confirmed that HOTAIR rs2366152 and rs1899663 polymorphisms associated with CRC risk in different inheritance models. It is indeed necessary to do additional research to verify our findings., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Circulating microRNAs (miRNAs) can help to predict the chemotherapy response in breast cancer with promising results. The aim of the present study was to investigate the relationships between the miR-199a, miR-663a, and miR-663b expression and chemotherapy response in metastatic breast cancer patients., Methods: This study is a case-control study performed at Yasuj University of Medical Sciences (2018-2021). The expression levels of miR-663a, miR-663b, and miR-199a in the serum of 25 patients with metastatic breast cancer versus 15 healthy individuals were determined by the real-time polymerase chain reaction method. The response to treatment was followed up in a 24-month period. All patients were treated with second-line medications. Two or more combinations of these drugs were used: gemcitabine, Navelbine ® , Diphereline ® , Xeloda ® , letrozole, Aromasin ® , and Zolena ® . Statistical analyses were performed in SPSS 21.0 and GraphPad Prism 6 software. The expression levels were presented as mean±SD and analyzed by Student's t test., Results: The results and clinicopathological features of patients were analyzed by t test. The statistical analysis showed that miR-663a expression was related to human epidermal growth factor receptor 2 (HER2) status and was significantly lower in the HER2 + than HER2 - group (P=0.027). Moreover, the expression of miR-199a and miR-663b was significantly correlated with the response to treatment, in which the expression of miR-199a was higher in the poor-response group (P=0.049), while the higher expression of miR-663b was seen in the good-response group (P=0.009)., Conclusion: These findings state that the high plasma level of miR-199a and the low plasma level of miR-663b may be related to chemoresistance in patients with metastatic breast cancer., Competing Interests: Dr. Mehdi Dehghani, as the Editorial Board Member, was not involved in any stage of handling this manuscript. A team of independent experts were formed by the Editorial Board to review the article without his knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Selection and breeding for high-yielding in oilseed rape have always been one of the leading objectives for oilseed rape breeders. This process becomes more complicated when all quantitative traits are considered in selection in addition to grain yield. In the present study, 18 oilseed rape genotypes along with 2 check cultivars (RGS003 and Dalgan) were evaluated across 16 environments (a combination of 2 years and eight locations) in the tropical climate regions of Iran during 2018-2019 and 2019-2020 cropping seasons. The experiments were conducted in a format of randomized complete block design (RCBD) with three replications. The obtained multienvironmental trial data were utilized to conduct multivariate analysis, genotype by trait (GT) biplot, and genotype by yield*trait (GYT) biplot (Breeding, Genetics and Genomics, 1:2019). The GT and GYT biplot accounted for 55.5% and 93.6% of the total variation in the first two main components. Based on multivariate analysis and GT biplot, pod numbers in plant (PNP) and plant height (PH) were chosen as two key traits in spring oilseed rape genotypes for indirect selection due to high variation, strong positive correlation with grain yield (GY), and their high representatively and discriminability in genotype selection. The mean × stability GT biplot represented G10 (SRL-96-17) as the superior genotype. Based on the mean × stability GYT biplot, eight above-average genotypes were identified that took high scores in stability, high-yielding, and all evaluated quantitative traits at the same time. Based on the superiority index of GYT data, G10 (SRL-96-17) and G5 (SRL-96-11) indicated the best yield-trait combinations profile and ranked above check cultivars and then selected as superior genotypes. Similarly, cluster analysis using the WARD method also separated eight superior genotypes. Based on the result of the present study, GT ad GYT methodologies are recommended for trait profiling and genotype selection in oilseed rape breeding projects, respectively., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: The evidence obtained from experimental studies suggests the tumor-suppressive effects of vitamin D by controlling the differentiation, proliferation, and apoptosis in cancerous cells. Furthermore, the deregulation of genes involved in vitamin D metabolism has been reported in several types of cancer., Methods: In the present study, we investigated the expression level of vitamin D metabolic pathway genes, including VDR, CYP3A4, RXRα, and GC, in colorectal cancer (CRC) samples compared with the adjacent tissues by using quantitative RT-PCR., Results: The results indicated significant downregulation of CYP3A4 and VDR genes in CRC tissues compared with the adjacent control tissues (p < 0.01). RXRA and GC expression levels did not show any significant alteration among the studied samples. Moreover, a positive correlation was observed between the expression level of CYP3A4 and VDR genes (p < 0.0001). ROC curve analysis also revealed the potential diagnostic power of CYP3A4 and VDR genes in CRC samples., Conclusion: Reduction in the expression of both CYP3A4 and VDR plays an important role in CRC due to the possible impairment in vitamin D metabolism. Further studies concerning the relationship between the expression of these genes and colorectal cancer pathogenesis and treatment are recommended., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Cholestasis is a disorder that the bile ducts were narrowed and bile acids are not released simply. Bile acids-induced liver damage is exacerbated by inflammation and oxidative stress. The goal of the current study was to investigate the protective impacts of fluvoxamine (Flu) on oxidant-antioxidant balance and inflammatory cytokines in the bile duct ligated (BDL) rats., Methods: Thirty-two male rats were arbitrarily allocated in 4 groups; sham-control (SC), SC+ 150 mg/kg Flu (SCF), bile duct ligation (BDL), and BDL+ 150 mg/kg Flu (BDLF). The rats received distilled water and Flu orally for one week. Biochemical analysis, hematoxylin and eosin staining, as well as oxidant/antioxidant status were evaluated. Also, the mRNA expression of TGF-β1, IL-1, TNF-α, and α-SMA were determined., Results: The findings indicated serum values of ALT, total bilirubin, and ALP slightly declined in the BDL + Flu group in contrast to BDL rats. The plasma protein carbonyl and inflammatory markers were markedly increased in the BDL group in contrast with SC group (P ≤ 0.05). Treatment with Flu in BDL rats markedly reduced the values of hepatic nitric oxide metabolite and malondialdehyde, plasma protein carbonyl, as well as TNF-α mRNA level (P ≤ 0.05). Histological parameters were improved in the BDL + Flu group in comparison to BDL merely rats., Conclusion: It seems that Flu declined oxidative stress probably by inhibiting lipid peroxidation, protein oxidation, and nitric oxide formation. Also, it reduced inflammation by decreasing TNF-α mRNA expression., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Methods: In this experimental study, 35 male Wistar rats (120-180 g) were divided into five groups ( n  = 7) as follows: intratracheal instillation of bleomycin (BLM, 7.5 IU/kg) was administered to group II. The third and fourth groups received BLM plus Stachys pilifera hydroalcoholic extract (SPHE) (300 mg/kg/day, gavage). Vitamin E (500 mg/kg/day, gavage) was given to group V in addition to BLM. After 14 days, the animals were euthanized to assess biochemical parameters and lung histopathology. Malondialdehyde (MDA), nitric oxide (NO), total thiol (TSH), and glutathione (GSH) levels were measured. In addition, hydroxyproline (HYP) levels along with histological changes in lung tissue were also assessed., Results: MDA, NO, and HYP elevations induced by BLM toxicity were significantly inhibited by SPHE (300 and 600 mg/kg), and Vit E. SPHE also significantly increased GSH and TSH levels in comparison to the BLM group.HPLC analyses showed the presence of thymol (55.47 ng/mL) and carvacrol (109.91 ng/mL) in SPHE as potential bioactive phenolic compounds., Conclusion: The results suggest that SPHE alleviates the development of BLM-induced pulmonary fibrosis by inhibiting the proliferation of fibroblasts mediated by antioxidant pathways. Other mechanisms underlying this Effect of SPHE need to be clarified through further research., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nazanin Danaei et al.)

Background: Among the common mental disorders in societies, depression is one of the most common mental disorders that affects all groups and classes of society. Students are among the groups with the highest rates of depression. Therefore, the need for a short and effective tool for screening and early detection of depression is felt. The aim of this research is to determine validity, reliability and the best cut-off point of the patient health questionnaires-9 (PHQ-9) and patient health questionnaires-2 (PHQ-2) in university students., Methods: This cross-sectional study was conducted on 246 students of Kermanshah University of medical science in Kermanshah province of Iran. They completed the PHQ-2, PHQ-9, and the Beck Depression Inventory-II (BDI-II). A structured interview was used to diagnose depression. To analyze the data, Cronbach's alpha for internal consistency, the intra-class correlation (ICC) for test-retest reliability, confirmatory factor analysis for construct validity, Pearson Correlation for Convergent validity, and receiver-operating characteristic (ROC) curve for Criterion validity was used., Results: The mean age of the participants was 20.43 ± 2.29. Cronbach's alpha coefficient for PHQ-9 and PHQ-2 was 0.82 and 0.80, respectively. The test-retest reliability based on intra-class correlation (ICC) for PHQ-9 and PHQ-2 after two weeks was 0.81 and 0.73, respectively ( P < 0.001). The correlation coefficient between the PHQ-9 and PHQ-2 with the BDI-II was 0.74 and 0.64, respectively ( P < 0.001). Confirmatory factor analysis showed that two-factor model and one factor model had good model fit. The best cut-off point score for the PHQ-9 was 10 with a sensitivity of 0.90 and specificity of 0.93, and the best cut-off point score for the PHQ-2 was 3 with the sensitivity of 0.71 and specificity of 0.92., Conclusions: The PHQ-9 and PHQ-2 are suitable tools to screen depression in the university students in Iran., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 International Journal of Preventive Medicine.)

At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN ® ; a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN ® is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN ® induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2 × 10 8 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN ® as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies., (© 2022. The Author(s).)

Background: Gnathodiaphyseal dysplasia (GDD) is an ultrarare autosomal dominant bone dysplasia characterized by cementoosseous lesions of the jawbones, bone fragility, frequent bone fractures at the young age, bowing of tubular bones, and diaphyseal sclerosis of long bones associated with generalized osteopenia. GDD is caused by point mutations in anoctamin-5 (ANO5) on chromosome 11p14.3. For the past few years, next generation sequencing (NGS) technology has facilitated the discovery of causative variants in genetically heterogeneous diseases., Methods: In this study, exome sequencing (ES) was performed using the DNA sample of the proband. Family histories and clinical information were collected through comprehensive medical examination and genetic counseling., Results: ES results identified a heterozygous variant, NM&#95;213599.3:c.1078T>C(p.Cys360Arg) in the ANO5 gene. Sanger sequencing was performed to confirm the detected pathogenic variant in DNA samples of the entire family (except deceased individuals), which segregated with the disease within the family. Finally, in silico analysis was applied to test the pathogenicity of the variant using various online software., Conclusion: In summary, our investigation identified a novel pathogenic variant in the ANO5, responsible for gnathodiaphyseal dysplasia in a large Iranian family. Therefore, based on the present study, this variant can be helpful for diagnosis and effective management of GDD patients., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose: The experience of healthcare transition from pediatric to adult care in cystic fibrosis (CF) remains poorly understood, particularly among racially and ethnically diverse adolescents and young adults (AYAs) with CF. The objective of this qualitative study was to explore the perspectives of a diverse sample of AYAs with CF at one urban academic medical center regarding healthcare transition., Design and Methods: Guided by qualitative descriptive methodology, we purposively selected AYAs who represented the pre and post transition experience: some AYAs had experienced the transition preparation program CF R.I.S.E. Demographic information and responsibility for self-management behaviors were collected using an online survey. Semi-structured video interviews were conducted following an iterative interview guide. A codebook directed inductive coding. QSR NVivo Version 12 software was used to organize the data., Results: 12 AYAs with CF were enrolled (25% female, 25% Black AYA, 33% Hispanic/Latina/o AYA, 50% White AYA; mean age 20.8 years). Three themes were identified: independent care of the whole self, preparing for change and the unknown and transition experiences vary., Conclusions: Not all participants experienced a smooth transition. Participants identified suggestions for the development of transition preparation interventions, specifically around involving AYAs in transition decisions and beginning transition preparation early in adolescence., Practice Implications: Participants expressed uncertainty about transition when they felt little control over the process or lacked sufficient information about adult care. Therefore, comprehensive early transition preparation for all AYAs with CF with a focus on involving AYAs in transition decisions is recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF- κ B) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collectively, hawthorn can be considered as one new target for the research and development of innovative drugs for the prevention or treatment of DM and related problems., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Izadpanah Gheitasi et al.)

Rationale: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa . This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV 1 ) and greater reduction in P. aeruginosa sputum in response to tobramycin., Methods: A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection., Results: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV 1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log 10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043)., Conclusions: Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin., Competing Interests: Competing interests: DN and NM-H, as part of their roles at the Cystic Fibrosis (CF) Foundation Therapeutics Development Network Coordinating Centre, provide consulting to industry sponsors who are developing new drug therapies for cystic fibrosis. Some of these sponsors are working to develop antimicrobial agents. PS and DN report grants from Vertex and Gilead Sciences outside of the published work. RG and GR-B report grants from Vertex outside of the published work. LS reports grants from Merck Co and Bill and Melinda Gates Foundation outside of the published work and payments for Data Safety Monitoring Board or Advisory Boards from Merck Co. Multiple authors have grant support or payments from the CF Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown., Methods: We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF., Results: There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19., Conclusions: The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)