Clinical profiles and in-hospital short-term outcomes of suspect, probable, and confirmed adult COVID-19 patients at the Philippine Heart Center: A descriptive study

Introduction@#COVID-19 emerged as a new disease during the early period of 2020. Given that our institution is a cardiac specialty center and our patients have numerous co-morbidities compared to the general population, we wanted to determine the clinical profiles and in-hospital short-term outcomes of suspect, probable and confirmed adult COVID-19 patients seen at our institution.@*Methodology@#We prospectively enrolled 323 adult (115 health care workers) suspect, probable and confirmed COVID- 19 patients admitted from March to June 2020. We described and analyzed their clinical presentation, and in-hospital outcomes.@*Results@#There were 117 (36.22%) RT-PCR positive patients with 36.53% confirmed, 13.00% probable and 50.46% suspect patients. For probable and confirmed patients, 25%, 21.25%, 23.13% 16.25% had no, mild, moderate, and severe symptoms, respectively with 14.28% critical cases. Over-all mortality rate for probable and confirmed cases was 25.54% with 91.3% mortality rate for critical cases. Co-morbidities with statistically significant association with severity of disease were as follows: hypertension, heart disease, cerebrovascular disease, diabetes mellitus and COPD.@*Conclusion@#During the early period of the COVID-19 pandemic, only 36.53% of cases admitted at our institution were COVID-19 confirmed by RT-PCR. One-third of the cases were severe and critical, with more clinical instability, increased inflammatory markers, and higher in-hospital morbidity and mortality.

Quantification of Efflorescences in Pustular Psoriasis Using Deep Learning / 대한의료정보학회지

Objectives@#Pustular psoriasis (PP) is one of the most severe and chronic skin conditions. Its treatment is difficult, and measurements of its severity are highly dependent on clinicians’ experience. Pustules and brown spots are the main efflorescences of the disease and directly correlate with its activity. We propose an automated deep learning model (DLM) to quantify lesions in terms of count and surface percentage from patient photographs. @*Methods@#In this retrospective study, two dermatologists and a student labeled 151 photographs of PP patients for pustules and brown spots. The DLM was trained and validated with 121 photographs, keeping 30 photographs as a test set to assess the DLM performance on unseen data. We also evaluated our DLM on 213 unstandardized, out-of-distribution photographs of various pustular disorders (referred to as the pustular set), which were ranked from 0 (no disease) to 4 (very severe) by one dermatologist for disease severity. The agreement between the DLM predictions and experts’ labels was evaluated with the intraclass correlation coefficient (ICC) for the test set and Spearman correlation (SC) coefficient for the pustular set. @*Results@#On the test set, the DLM achieved an ICC of 0.97 (95% confidence interval [CI], 0.97–0.98) for count and 0.93 (95% CI, 0.92–0.94) for surface percentage. On the pustular set, the DLM reached a SC coefficient of 0.66 (95% CI, 0.60–0.74) for count and 0.80 (95% CI, 0.75–0.83) for surface percentage. @*Conclusions@#The proposed method quantifies efflorescences from PP photographs reliably and automatically, enabling a precise and objective evaluation of disease activity.

Targeted massively parallel sequencing panel to diagnose genetic endocrine disorders in a tertiary hospital

Abstract Objectives To analyze the efficiency of a multigenic targeted massively parallel sequencing panel related to endocrine disorders for molecular diagnosis of patients assisted in a tertiary hospital involved in the training of medical faculty. Material and methods Retrospective analysis of the clinical diagnosis and genotype obtained from 272 patients in the Endocrine unit of a tertiary hospital was performed using a custom panel designed with 653 genes, most of them already associated with the phenotype (OMIM) and some candidate genes that englobes developmental, metabolic and adrenal diseases. The enriched DNA libraries were sequenced in NextSeq 500. Variants found were then classified according to ACMG/AMP criteria, with Varsome and InterVar. Results Three runs were performed; the mean coverage depth of the targeted regions in panel sequencing data was 249×, with at least 96.3% of the sequenced bases being covered more than 20-fold. The authors identified 66 LP/P variants (24%) and 27 VUS (10%). Considering the solved cases, 49 have developmental diseases, 12 have metabolic and 5 have adrenal diseases. Conclusion The application of a multigenic panel aids the training of medical faculty in an academic hospital by showing the picture of the molecular pathways behind each disorder. This may be particularly helpful in developmental disease cases. A precise genetic etiology provides an improvement in understanding the disease, guides decisions about prevention or treatment, and allows genetic counseling.

Ups and downs of hypertension control in Canada: critical factors and lessons learned / Altibajos en el control de la hipertensión en Canadá: factores críticos y lecciones aprendidas / Altos e baixos no controle da hipertensão no Canadá: fatores críticos e lições aprendidas

ABSTRACT As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

RESUMEN La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

RESUMO O controle populacional da hipertensão arterial - o maior fator de risco de morte - representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Article-Level Metrics

In the era of digitization and Open Access, article-level metrics are increasingly employed to distinguish influential research works and adjust research management strategies. Tagging individual articles with digital object identifiers allows exposing them to numerous channels of scholarly communication and quantifying related activities. The aim of this article was to overview currently available article-level metrics and highlight their advantages and limitations. Article views and downloads, citations, and social media metrics are increasingly employed by publishers to move away from the dominance and inappropriate use of journal metrics. Quantitative article metrics are complementary to one another and often require qualitative expert evaluations. Expert evaluations may help to avoid manipulations with indiscriminate social media activities that artificially boost altmetrics. Values of article metrics should be interpreted in view of confounders such as patterns of citation and social media activities across countries and academic disciplines.

Surgical revascularization for Moyamoya disease in the United States: A cost-effectiveness analysis

Objective@#Moyamoya disease (MMD) is a vasculopathy of the internal carotid arteries with ischemic and hemorrhagic sequelae. Surgical revascularization confers upfront peri-procedural risk and costs in exchange for long-term protective benefit against hemorrhagic disease. The authors present a cost-effectiveness analysis (CEA) of surgical versus non-surgical management of MMD. @*Methods@#A Markov Model was used to simulate a 41-year-old suffering a transient ischemic attack (TIA) secondary to MMD and now faced with operative versus nonoperative treatment options. Health utilities, costs, and outcome probabilities were obtained from the CEA registry and the published literature. The primary outcome was incremental cost-effectiveness ratio which compared the quality adjusted life years (QALYs) and costs of surgical and nonsurgical treatments. Base-case, one-way sensitivity, two-way sensitivity, and probabilistic sensitivity analyses were performed with a willingness to pay threshold of $50,000. @*Results@#The base case model yielded 3.81 QALYs with a cost of $99,500 for surgery, and 3.76 QALYs with a cost of $106,500 for nonsurgical management. One-way sensitivity analysis demonstrated the greatest sensitivity in assumptions to cost of surgery and cost of admission for hemorrhagic stroke, and probabilities of stroke with no surgery, stroke after surgery, poor surgical outcome, and death after surgery. Probabilistic sensitivity analyses demonstrated that surgical revascularization was the cost-effective strategy in over 87.4% of simulations. @*Conclusions@#Considering both direct and indirect costs and the postoperative QALY, surgery is considerably more cost-effective than non-surgical management for adults with MMD.

Article-Level Metrics

In the era of digitization and Open Access, article-level metrics are increasingly employed to distinguish influential research works and adjust research management strategies. Tagging individual articles with digital object identifiers allows exposing them to numerous channels of scholarly communication and quantifying related activities. The aim of this article was to overview currently available article-level metrics and highlight their advantages and limitations. Article views and downloads, citations, and social media metrics are increasingly employed by publishers to move away from the dominance and inappropriate use of journal metrics. Quantitative article metrics are complementary to one another and often require qualitative expert evaluations. Expert evaluations may help to avoid manipulations with indiscriminate social media activities that artificially boost altmetrics. Values of article metrics should be interpreted in view of confounders such as patterns of citation and social media activities across countries and academic disciplines.

Surgical revascularization for Moyamoya disease in the United States: A cost-effectiveness analysis

Objective@#Moyamoya disease (MMD) is a vasculopathy of the internal carotid arteries with ischemic and hemorrhagic sequelae. Surgical revascularization confers upfront peri-procedural risk and costs in exchange for long-term protective benefit against hemorrhagic disease. The authors present a cost-effectiveness analysis (CEA) of surgical versus non-surgical management of MMD. @*Methods@#A Markov Model was used to simulate a 41-year-old suffering a transient ischemic attack (TIA) secondary to MMD and now faced with operative versus nonoperative treatment options. Health utilities, costs, and outcome probabilities were obtained from the CEA registry and the published literature. The primary outcome was incremental cost-effectiveness ratio which compared the quality adjusted life years (QALYs) and costs of surgical and nonsurgical treatments. Base-case, one-way sensitivity, two-way sensitivity, and probabilistic sensitivity analyses were performed with a willingness to pay threshold of $50,000. @*Results@#The base case model yielded 3.81 QALYs with a cost of $99,500 for surgery, and 3.76 QALYs with a cost of $106,500 for nonsurgical management. One-way sensitivity analysis demonstrated the greatest sensitivity in assumptions to cost of surgery and cost of admission for hemorrhagic stroke, and probabilities of stroke with no surgery, stroke after surgery, poor surgical outcome, and death after surgery. Probabilistic sensitivity analyses demonstrated that surgical revascularization was the cost-effective strategy in over 87.4% of simulations. @*Conclusions@#Considering both direct and indirect costs and the postoperative QALY, surgery is considerably more cost-effective than non-surgical management for adults with MMD.

Performance of mutation pathogenicity prediction tools on missense variants associated with 46, XY differences of sex development

OBJECTIVES: Single nucleotide variants (SNVs) are the most common type of genetic variation among humans. High-throughput sequencing methods have recently characterized millions of SNVs in several thousand individuals from various populations, most of which are benign polymorphisms. Identifying rare disease-causing SNVs remains challenging, and often requires functional in vitro studies. Prioritizing the most likely pathogenic SNVs is of utmost importance, and several computational methods have been developed for this purpose. However, these methods are based on different assumptions, and often produce discordant results. The aim of the present study was to evaluate the performance of 11 widely used pathogenicity prediction tools, which are freely available for identifying known pathogenic SNVs: Fathmn, Mutation Assessor, Protein Analysis Through Evolutionary Relationships (Phanter), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, Polymorphism Phenotyping v2 (Polyphen-2), Align Grantham Variation Grantham Deviation (Align-GVGD), CAAD, Provean, SNPs&GO, and MutPred. METHODS: We analyzed 40 functionally proven pathogenic SNVs in four different genes associated with differences in sex development (DSD): 17β-hydroxysteroid dehydrogenase 3 (HSD17B3), steroidogenic factor 1 (NR5A1), androgen receptor (AR), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). To evaluate the false discovery rate of each tool, we analyzed 36 frequent (MAF>0.01) benign SNVs found in the same four DSD genes. The quality of the predictions was analyzed using six parameters: accuracy, precision, negative predictive value (NPV), sensitivity, specificity, and Matthews correlation coefficient (MCC). Overall performance was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Our study found that none of the tools were 100% precise in identifying pathogenic SNVs. The highest specificity, precision, and accuracy were observed for Mutation Assessor, MutPred, SNP, and GO. They also presented the best statistical results based on the ROC curve statistical analysis. Of the 11 tools evaluated, 6 (Mutation Assessor, Phanter, SIFT, Mutation Taster, Polyphen-2, and CAAD) exhibited sensitivity >0.90, but they exhibited lower specificity (0.42-0.67). Performance, based on MCC, ranged from poor (Fathmn=0.04) to reasonably good (MutPred=0.66). CONCLUSION: Computational algorithms are important tools for SNV analysis, but their correlation with functional studies not consistent. In the present analysis, the best performing tools (based on accuracy, precision, and specificity) were Mutation Assessor, MutPred, and SNPs&GO, which presented the best concordance with functional studies.

Targeted massively parallel sequencing for congenital generalized lipodystrophy

ABSTRACT Objective: Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). Subjects and methods: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. Results: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. Conclusions: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.

Antiplatelet therapy within 24 hoursof tPA: lessons learned from patientsrequiring combined thrombectomyand stenting for acute ischemic stroke

Objective@#Although stroke guidelines recommend antiplatelets be started 24 hoursafter tissue plasminogen activator (tPA), select mechanical thrombectomy (MT)patients with luminal irregularities or underlying intracranial atherosclerotic diseasemay benefit from earlier antiplatelet administration. @*Methods@#We explore the safety of early (< 24 hours) post-tPA antiplatelet use byretrospectively reviewing patients who underwent MT and stent placement for acuteischemic stroke from June 2015 to April 2018 at our institution. @*Results@#Six patients met inclusion criteria. Median presenting and pre-operativeNational Institutes of Health Stroke Scale scores were 14 (Interquartile Range [IQR]5.5-17.3) and 16 (IQR 13.7-18.7), respectively. Five patients received standard intravenous(IV) tPA and one patient received intra-arterial tPA. Median time from symptomonset to IV tPA was 120 min (IQR 78-204 min). Median time between tPA and antiplateletadministration was 4.9 hours (IQR 3.0-6.7 hours). Clots were successfullyremoved from the internal carotid artery (ICA) or middle cerebral artery (MCA) in 5patients, the anterior cerebral artery (ACA) in one patient, and the vertebrobasilarjunction in one patient. All patients underwent MT before stenting and achievedthrombolysis in cerebral infarction 2B recanalization. Stents were placed in the ICA(n=4), common carotid artery (n=1), and basilar artery (n=1). The median time fromstroke onset to endovascular access was 185 min (IQR 136-417 min). No patientsexperienced symptomatic post-procedure intracranial hemorrhage (ICH). Medianmodified Rankin Scale score on discharge was 3.5. @*Conclusions@#Antiplatelets within 24 hours of tPA did not result in symptomatic ICHin this series. The safety and efficacy of early antiplatelet administration after tPA inselect patients following mechanical thrombectomy warrants further study.

Does surgical procedure type impact postoperative pain and recovery in deep inferior epigastric artery perforator flap breast reconstruction?

Background@#The deep inferior epigastric artery perforator (DIEP) flap is the commonest flap used for breast reconstruction after mastectomy. It is performed as a unilateral (based on one [unipedicled] or two [bipedicled] vascular pedicles) or bilateral procedure following unilateral or bilateral mastectomies. No previous studies have comprehensively analyzed analgesia requirements and hospital stay of these three forms of surgical reconstruction. @*Methods@#A 7-year retrospective cohort study (2008–2015) of a single-surgeon’s DIEP-patients was conducted. Patient-reported pain scores, patient-controlled morphine requirements and recovery times were compared using non-parametric statistics and multivariable regression. @*Results@#The study included 135 participants: unilateral unipedicled (n=84), unilateral bipedicled (n=24) and bilateral unipedicled (n=27). Univariate comparison of the three DIEP types showed a significant difference in 12-hour postoperative morphine requirements (P=0.020); bipedicled unilateral patients used significantly less morphine than unipedicled (unilateral) patients at 12 (P=0.005), 24 (P=0.020), and 48 (P=0.046) hours. Multivariable regression comparing these two groups revealed that both reconstruction type and smoking status were significant predictors for 12-hour postoperative morphine usage (P=0.038 and P=0.049, respectively), but only smoking, remained significant at 24 (P=0.010) and 48 (P=0.010) hours. Bilateral reconstruction patients’ mean hospital stay was 2 days longer than either unilateral reconstruction (P<0.001). @*Conclusions@#Although all three forms of DIEP flap breast reconstruction had similar postoperative pain measures, a novel finding of our study was that bipedicled DIEP flap harvest might be associated with lower early postoperative morphine requirements. Bilateral and bipedicled procedures in appropriate patients might therefore be undertaken without significantly increased pain/morbidity compared to unilateral unipedicled reconstructions.

Update on new GH-IGF axis genetic defects

ABSTRACT The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17

Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery

ABSTRACT The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74

Genetic causes of isolated short stature

ABSTRACT Short stature is a common feature, and frequently remains without a specific diagnosis after conventional clinical and laboratorial evaluation. Longitudinal growth is mainly determined by genetic factors, and hundreds of common variants have been associated to height variability among healthy individuals. Although isolated short stature may be caused by the combination of variants, with a deleterious impact on the growth of individuals with polygenic inheritance, recent studies have pointed out some monogenic defects as the cause of the growth disorder observed in nonsyndromic children. The majority of these defects are in genes related to the growth plate cartilage and in the growth hormone (GH) - insulin-like growth factor 1 (IGF-1) axis. Affected patients usually present the mildest spectrum of some forms of skeletal dysplasia, or subtle abnormalities of laboratory tests, suggesting hormonal resistance or insensibility. The lack of specific characteristics, however, does not allow formulation of a definitive diagnosis without the use of broad genetic studies. Thus, molecular genetic studies including panels of genes or exome analysis will become essential in investigating and identifying the causes of isolated short stature in children, with a crucial impact on treatment and follow-up.

Comprehensive Approach to Open Access Publishing: Platforms and Tools

The Open Access Initiative is gaining momentum due to the worldwide availability of advanced digital tools, online publishing platforms, and systems for tracking academic contributions. Several declarations and initiatives, including Plan S, have already laid a foundation for moving away from subscription to full and immediate open-access publishing. The global initiatives imply targeting journals satisfying the upgraded quality and visibility criteria. To meet these criteria, a comprehensive approach to Open Access is recommended. This article overviews the essential components of the comprehensive approach, increasing transparency, adherence to ethical standards, and diversification of evaluation metrics. With the increasing volume of quality open-access journals, their indexing with free databases and search engines is becoming increasingly important. The Directory of Open Access Journals and PubMed Central currently free searches of open-access sources. These services, however, cannot fully satisfy the increasing demands of the users, and attempts are underway to upgrade the indexing and archiving of open-access sources in China, Japan, Korea, Russia, and elsewhere. The wide use of identifiers is essential for transparency of scholarly communications. Peer reviewers are now offered credits from Publons. These credits are transferrable to their Open Researcher and Contributor iDs. Various social media channels are increasingly used by scholars to comment on articles. All these comments are tracked by related metric systems, such as Altmetrics. Combined with traditional citation evaluations, the alternative metrics can help timely identify and promote publications influencing education, research, and practice.

Updated Editorial Guidance for Quality and Reliability of Research Output

Over the past few years, updated editorial policy statements of several associations have provided a platform for improving the quality of scientific research and publishing. The updates have particularly pointed to the need for following research reporting standards, authorship and contributorship regulations, implementing digital tools for the identification and crediting academic contributors, and moving towards optimal ethical open-access models. This article overviews some of the recent editorial policy statements of global editorial associations and reflects on the role of the regional counterparts in advancing scholarly publishing. One of the globally promoted documents is the Recommendations of the International Committee of Medical Journal Editors (ICMJE). Its latest versions contain statements on proper research reporting, reviewing, editing, and publishing. Points on ethical target journals and ‘predatory’ sources are also available. This year, in a move to update its editorial policy, the Committee on Publication Ethics (COPE) released the Core Practices, comprehensively reflecting on the major issues in publication ethics. Updated joint statements of medical writers associations are also available to implement transparent policy on contributorship in sponsor-supported research projects and related reports. Several suggestions are put forward to improve global editorial statements on online profiling, crediting, and referencing. It is also highlighted that knowledge and implementation of updated editorial guidance is essential for editors' good standing.

Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing

SUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.

Identification of phenolic compounds in Myricaria bracteata leaves by high-performance liquid chromatography with a diode array detector and liquid chromatography with tandem mass spectrometry

Abstract Myricaria bracteata Royle, Tamaricaceae, is a species with a wide geographic range that encompasses Eastern Europe, Western and Central Siberia, Central Asia, and the Himalayas. This plant is used in traditional folk medicine in Russia (Siberia) and in China typically as an analgesic and for the treatment of some infections and certain types of intoxication. The aim of this study was to identify phenolic constituents of the leaves of M. bracteata from two considerably distant populations. Chromatographic profiles of the leaves of M. bracteata were analyzed for the first time. Seventeen compounds, mainly methyl ethers of quercetin (isorhamnetin, rhamnazin), kaempferol (kaempferide, rhamnocitrin), and ellagic acid as well as quercetin, quercetin 3-glucoside, kaempferol, luteolin, chrysoeriol, citric acid, gallic acid, methyl gallate, ethyl gallate, and ferulic acid were identified in hydrolyzed aqueous ethanol extracts of the leaves. Flavonols and ellagic acid were the major compounds in both samples. Isorhamnetin was the main flavonoid constituent. Kaempferide and rhamnazin were also abundant in the flavonoid complex of the leaves of M. bracteata from the Altai. This study shows that M. bracteata leaves are a source of flavonoids with possible biological activities.

Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect

ABSTRACT Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping for STAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.