bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic testing in patients with triple-negative or hereditary breast cancer
Authors: Bernstein-Molho Rinat , Evron Ella , Yerushalmi Rinat , Paluch-Shimon Shani 
Published: September 2021

Purpose of review
In recent years there has been a dramatic evolution in the clinical utility of genetic testing with expanding therapeutic implications for individuals with breast cancer who harbor a germline mutation in BRCA1/2. As these therapeutic opportunities expand and evolve, this requires the clinical and research community to rethink the approach to genetic testing for individuals with breast cancer.

Recent findings
Genetic testing is evolving from traditional testing models based on pretest counseling with the aim of identifying hereditary and individual risk for purposes of screening and risk reduction to contemporary models that utilize technology to improve accessibility and oncology led mainstreaming of testing where the oncologist refers for genetic testing, discloses the results and formal counseling occurs later in the process than in traditional models. The cost and accessibility to multigene panel testing have resulted in broad uptake despite the fact that clinical utility and appropriate interpretation of results are not yet well established. Furthermore, somatic testing for genomic alterations may also yield results beyond the disease with detection of germline mutations impacting the individual and their family more broadly than anticipated.

Summary
With the establishment of poly (adenosine diphosphate-ribose) polymerase inhibitors as part of the treatment armamentarium for early and advanced breast cancer, paradigms, algorithms, and resources for genetic testing need to rapidly change in order to adapt to the evolution of germline mutations from hereditary and individual risk predictors to predictive therapeutic biomarkers.
Advances in myelodysplastic syndrome
Authors: Santini Valeria 
Published: September 2021

Purpose of review
In this review, the focus is on the most recent improvements in diagnosis, prognostication and therapy of myelodysplastic syndromes (MDS) and on their relevance for clinical management.

Recent findings
Analytical methods to refine cytogenetic and molecular assessment of MDS have been proposed, improving prognostic stratification obtained from integration of clinical and genomic data. Novel agents with very different mode of action, as single drugs or added to HMA backbone, show promising clinical results in LR-MDS and HR-MDS. Luspatercept has obtained approval given the fact that in transfusion-dependent erythropoietic-stimulating agent resistant/relapsed LR-MDS induced nearly 50% of transfusion independence. Another investigational agent showing efficacy and possibly disease modifying activity in the same setting is the telomerase inhibitor imetelstat. Results from phase II study with azacytidine and pevonedistat indicate the concrete possibility to enhance durable responses compared with azacitidine single drug. In the same direction are the preliminary results of other agents with different mode of action: magrolimab, venetoclax, sabatolimab, as well as the targeted therapy with enasidenib and ivosidenib. New posttransplant maintenance strategies may concur to prolong response.

Summary
Better diagnosis and prognostic stratification may allow a more precise and personalized treatment of MDS with novel agent combinations leading to improved therapeutic algorithms.
Recognizing the Trauma of Adverse Childhood Experiences
Authors: Cole Britt S. 
Published: September 2021

ABSTRACT:
Childhood trauma is linked to long-term negative health outcomes throughout the lifespan and is recognized as a public health crisis. Using the framework of the four main components of trauma-informed care is a beginning step in meeting the deep, unmet needs of adult patients with sensitivity and awareness. Christian nurses recognize Jesus as the first trauma-informed provider and model his relational characteristics as they promote healing from trauma.
An update on neuropsychiatric adverse effects with second-generation integrase inhibitors and nonnucleoside reverse transcriptase inhibitors
Authors: Senneker Tessa , Tseng Alice 
Published: September 2021

Purpose of review
Neuropsychiatric adverse effects (NPAE) associated with integrase strand transfer inhibitors (INSTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a growing concern, with higher rates in the real-world compared to phase III trials. This paper reviews the incidence, risk factors, and management of NPAE with second-generation INSTIs, INSTI/rilpivirine dual therapy, and doravirine.

Recent findings
Recent cohort data confirm up to 8% NPAE-associated discontinuations for dolutegravir; NPAE with dolutegravir/rilpivirine therapy are higher than with dolutegravir alone, whereas bictegravir appears similar to dolutegravir. In contrast, NPAE with cabotegravir alone or with rilpivirine appears to be low. Doravirine has NPAE rates similar to rilpivirine and lower than efavirenz. Risk factors for NPAE include female gender, concurrent abacavir use, Sub-Saharan African descent, and age, whereas underlying psychiatric conditions do not appear to increase risk. Strategies to manage NPAE include changing administration time, therapeutic drug monitoring, or regimen modification including within-class INSTI changes. People experiencing NPAE with dolutegravir may tolerate bictegravir.

Summary
Overall, mild to moderate NPAE are associated with INSTIs and newer NNRTIs. Rarely, more severe symptoms may occur and lead to treatment discontinuation. Clinicians should be aware of NPAE to identify and manage drug-related adverse effects.
Accuracy of the oscillometric method for the measurement of heart rate at rest and during mild exercise
Authors: Palatini Paolo , Lazzaretto Ilaria , Fontana Umberto , Fania Claudio 
Published: September 2021

Objective:
Whether oscillometric devices provide accurate measurements of heart rate (HR) is not known. Our aim was to determine the accuracy of an oscillometric device for the measurement of HR during rest and exercise.

Methods:
The Microlife WatchBP O3, a monitor previously validated for blood pressure measurement, was tested in 36 individuals from the general population (mean age, 72.9 years; 18 men). HR was measured at rest and during stress testing on a cycle ergometer in order to increase HR by 15% or more. HR was computed from the oscillometric waves recorded during the deflation phase of the blood pressure measurement and was compared with HR measured by pulse palpation by two observers.

Results:
At rest, the mean device–observer HR difference was 0.9 ± 2.1 bpm. During exercise, the average HR increase was 20.3% and the mean device–observer difference was 0.6 ± 2.6 bpm. The device–observer HR differences were all included within ±6 bpm both at rest and during exercise. Kappa statistics showed a very good agreement between device and observers both at rest (kappa scores, 0.82–0.88) and during exercise (kappa scores, 0.81 and 0.86). The device–observer HR differences were unrelated to the level of HR or to pulse pressure.

Conclusion:
The present study shows that the oscillometric technique is able to provide reliable HR measurements during rest and mild exercise. Whether evaluation of HR performance should be included during validation testing of automatic monitors should be established by regulatory bodies.
Dietary sodium intake and sodium load is associated with arterial stiffness in children and young adults
Authors: Brady Tammy M. , Horst Gilbert , Appel Lawrence J. , Khoury Philip R. , Urbina Elaine M. 
Published: September 2021

Objective:
The aim of this study was to examine the association of sodium intake (g/day) and sodium load (Na-L; mg/kcal/day) on arterial stiffness in youth.

Methods:
A cross-sectional analysis of 723 youth enrolled in a study evaluating the cardiovascular effects of obesity and type 2 diabetes mellitus (T2DM). Three measures of arterial stiffness were evaluated: brachial distensibility (BrachD), carotid-femoral pulse wave velocity (PWVcf) and augmentation index (AIx). Three-day diet histories yielded mean daily sodium and calorie intake. Youth were divided into Na-L tertiles: Low (≤1.67 mg/kcal per day); Medium (1.68--1.98 mg/kcal per day) and High (>1.98 mg/kcal per day). General linear models adjusting for demographics, % body fat, T2DM and SBP z-score evaluated the independent association of Na-L with arterial stiffness

Results:
Mean age was 17.9 years (10–24 years), 35% male, 59% nonwhite and 31% T2DM. Mean (±standard deviation) dietary intake was calories = 2074 (±797) kcal/day; Na = 3.793 (±1567) g/day; Na- = 1.86 (±0.753) mg/kcal per day. With higher levels of dietary Na intake and Na-L, measures of arterial stiffness worsened: BrachD decreased (Na intake: beta = −0.09, P = 0.003; Na-L: beta = −0.28, P < 0.0001), PWVcf increased (Na intake: beta = 0.07, P = 0.007; Na-L: beta = 0.21, P < 0.0001) but AIx did not change (Na intake: beta = −0.4, P = 0.2; Na-L: beta = 0.89, P = 0.11). In multivariable analysis, High Na-L was independently associated with BrachD, PWVcf and AIx (P < 0.05 for all), with age modifying the association of High Na-L with PWVcf and AIx.

Conclusion:
Sodium intake and load are associated with arterial stiffness, a preclinical measure of CVD, among a paediatric population. Paediatricians should stress healthy dietary choices to reduce accelerated vascular ageing.
Clinical Utility of Bruch Membrane Opening–Minimum Rim Width for Detecting Early Glaucoma in Myopic Eyes
Authors: Park Do Hee , Kook Kyung Yoon , Kang Yeon Soo , Piao Helong , Sung Mi Sun , Park Sang Woo 
Published: September 2021

Précis:
Bruch membrane opening–minimum rim width (BMO-MRW) is overall a useful parameter for diagnosing early glaucoma in myopic eyes.

Purpose:
The aim of this study was to determine the diagnostic value of BMO-MRW compared with peripapillary retinal nerve fiber layer (pRNFL) thickness for detecting early glaucoma in patients with moderate to severe myopia.

Methods:
One eye was randomly selected from each of the 253 subjects (127 normal controls, 82 with glaucoma suspect, and 44 with early glaucoma). All patients underwent visual acuity testing, refractive error assessment, slit-lamp inspection, intraocular pressure measurement, fundus photography, perimetry. BMO-MRW and pRNFL thickness data were obtained using spectral-domain optical coherence tomography. Area under the receiver operating characteristic curves (AUC) for global and sectoral thickness parameters were calculated.

Results:
Global analyses for the discrimination of early glaucoma in all myopic subjects showed comparable AUCs between BMO-MRW and pRNFL thickness [AUC 0.952 (95% confidence interval, 0.918-0.975) and 0.934 (95% confidence interval, 0.896-0.961), respectively, P=0.345]. However, in sectoral analysis, BMO-MRW showed significantly better diagnostic performance than pRNFL thickness except for the superotemporal sector. The AUC for discriminating early glaucoma from glaucoma suspect, BMO-MRW showed statistically better diagnostic performance in the inferotemporal, inferonasal, superonasal, and nasal sectors. When dividing the subject based on a threshold Bruch membrane opening (BMO) area of 2.5 mm2, the diagnostic power of BMO-MRW was generally lower except for the inferonasal sector in the subgroup with a large BMO area.

Conclusions:
BMO-MRW was overall a useful parameter for diagnosing early glaucoma in myopic eyes. However, its diagnostic performance was decreased in myopic eyes with large BMO and there were no significant differences from pRNFL thickness.
Strengthening the US Response to Resistant Gonorrhea: An Overview of a Multisite Program to Enhance Local Response Capacity for Antibiotic-Resistant Neisseria gonorrhoeae
Authors: Schlanger Karen , Learner Emily R. , Pham Cau D. , Mauk Kerry , Golden Matthew , Wendel Karen A. , Amsterdam Lori , McNeil Candice J. , Johnson Kimberly , Nguyen Trang Quyen , Holderman Justin L. , Hasty Gerald L. , St. Cyr Sancta B. , Town Katy , Nash Evelyn E. , Kirkcaldy Robert D. ,   for the SURRG Working Group
Published: September 2021

Background
In 2016, Centers for Disease Control and Prevention initiated Strengthening the US Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies.

Methods
Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in sexually transmitted disease and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin.

Results
Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018 to 2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% [3412] and 8.9% [4883] of local reported cases in 2018 and 2019, respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts.

Conclusions
As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed.
How the Disruption in Sexually Transmitted Infection Care Due to the COVID-19 Pandemic Could Lead to Increased Sexually Transmitted Infection Transmission Among Men Who Have Sex With Men in The Netherlands: A Mathematical Modeling Study
Authors: Xiridou Maria , Heijne Janneke , Adam Philippe , Op de Coul Eline , Matser Amy , de Wit John , Wallinga Jacco , van Benthem Birgit 
Published: September 2021

Background
During the COVID-19 pandemic, the disruption in care for sexually transmitted infections (STIs) and the social distancing measures have led to reductions in STI testing and sexual behavior. We assessed the impact of these COVID-19–related changes on transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among men who have sex with men (MSM) in The Netherlands.

Methods
We developed a mathematical model for CT and NG transmission among MSM, accounting for COVID-19–related changes in sexual behavior and testing in 2020 to 2021. Changes in 2020 were estimated from data from the Dutch COVID-19, Sex, and Intimacy Survey among MSM and the National Database of STI Clinics. Because of the lack of data for 2021, we examined several scenarios covering a range of changes.

Results
A reduction of 10% and 40% in STI testing of symptomatic and asymptomatic, respectively, individuals with a 10% to 20% reduction in numbers of casual partners (according to partner status and activity level) during the second lockdown, resulted in a 2.4% increase in CT prevalence, but a 2.8% decline in NG prevalence in 2021. A 5% and 30% reduction in STI testing of symptomatic and asymptomatic, respectively, individuals with the same reduction in casual partners resulted in a 0.6% increase in CT prevalence and a 4.9% decrease in NG prevalence in 2021.

Conclusions
The disruption in STI care due to COVID-19 might have resulted in a small increase in CT prevalence, but a decrease in NG prevalence. Scaling up STI care is imperative to prevent increases in STI transmission.
Evaluating the Efficacy of Eradicating Gardnerella vaginalis Vaginal Colonization With Amoxicillin: A Randomized, Double-Blind, Phase 2 Study
Authors: McNeil Candice J. , Tan Amy , Powell Jonathan A. , Pontius Angela , Lewis Andrea , Myler Noelle , Schwebke Jane R. 
Published: September 2021

Background
Research suggests that Gardnerella vaginalis (GV) is the keystone pathogen in bacterial vaginosis (BV). Knowledge gaps exist regarding the role of GV eradication in the development of BV. This study was designed to test the hypothesis that vaginal colonization with GV could be eradicated by treatment of women without BV with amoxicillin, a drug highly active against GV. If GV is necessary for the development of BV, then eradication of GV may prevent the development of BV.

Methods
We conducted a randomized control trial of amoxicillin 500 mg twice daily versus placebo for 7 days in women aged 18 to 45 years without vaginitis who screened positive for vaginal colonization with GV by quantitative polymerase chain reaction. Test-of-cure visit for GV was conducted at day 21.

Results
One hundred seventy-two women met preliminary criteria and were screened for enrollment. Ninety-seven GV-positive women were randomized to receive amoxicillin versus placebo. Eradication of GV occurred in 21% of women randomized to amoxicillin versus 16% on placebo (P = 0.757). In the 4 weeks between screening and test-of-cure visit, 16 of 92 (17%) of participants developed Nugent scores greater than 3 with 8 of 92 (9%) having BV. All of these were in participants in whom GV was not eradicated (P = 0.035).

Conclusions
The study failed to show a benefit of treatment with amoxicillin to eradicate GV. No participants in whom GV was eradicated had progression to abnormal vaginal flora during the study period.
Novel Evaluation of Submandibular Salivary Gland Tissue for Use as an Alternative Postmortem Toxicology Specimen
Authors: Morton Ernest , Prahlow Joseph A. , Ianni Julie , Jones Prentiss 
Published: September 2021

Abstract
The collection of blood and tissue provides an opportunity for an objective comparison of autopsy results. Occasionally, a viable tissue sample is not available during autopsy. Expanding upon collected tissues to include a tissue that is accessible, is a possible drug depot, and is amendable to various analytical techniques may complement information obtained from other specimens. Given its absorption of ions, nutrients, and likely drugs via its rich blood supply, we evaluated the use of submandibular salivary gland tissue as an alternative postmortem specimen. The submandibular salivary glands of 52 decedents were excised. The tissue was homogenized, extracted, and analyzed via liquid chromatography tandem mass spectrometry for 43 opioids and 5 nonopioids. Liquid chromatography tandem mass spectrometry salivary tissue results were compared with the decedent's blood results. Results revealed that opioids were detected in salivary gland tissue at a sensitivity and specificity of 94.4% and 94.1%, respectively. Nonopioid drugs were detected at a sensitivity and specificity of 88.2% and 100.0%, respectively. This study suggests a comparable correlation exists between salivary gland tissue and blood results for certain drugs. Further evaluation is warranted. To our knowledge, this is the first report of salivary gland tissue being used for postmortem toxicology testing in humans.
Rhabdomyosarcoma—Updated Histologic and Molecular Classification for 2021
Authors: Dashti Nooshin K. , Perry Kyle , Cates Justin M. M. 
Published: September 2021

Abstract
Rhabdomyosarcomas are the most common soft tissue sarcoma in children and adolescents, but some specific histologic subtypes occur in adult patients. They involve various soft tissue or visceral sites, and most follow an aggressive clinical course. Currently, rhabdomyosarcomas are classified into 4 distinct clinical and morphological subtypes: embryonal, alveolar, spindle cell/sclerosing, and pleomorphic. This article reviews the clinical, histopathologic, and updated genetic features of these rhabdomyosarcoma subtypes.
Primary Alveolar Soft Part Sarcoma Arising in the Thyroid Gland: A Rare Case Report
Authors: Aggarwal Ashna , Mansour Mena 
Published: September 2021

Background
Alveolar soft part sarcoma (ASPS) is a rare aggressive soft tissue sarcoma usually involving the soft tissue of thigh and buttock region in adults. In children, head and neck presentation is more common, with orbit and tongue being the preferred sites. Alveolar soft part sarcoma primarily arising in the thyroid gland is an extremely rare clinical entity, with only two other cases being reported in the literature to date.

Case
A 16-year-old boy presented with respiratory distress and enlarged thyroid gland. Hemithyroidectomy revealed well-circumscribed nests of large cells with abundant eosinophilic cytoplasm arranged in a pseudoalveolar pattern and separated by fibrous septa containing sinusoidal blood vessels. The tumor cells showed nuclear positivity for TFE3 protein and the TFE3 gene rearrangement in 79% of the nuclei. The patient's most recent chest computed tomography revealed multiple subcentimeter nodules occupying the lung bases emphasizing the aggressiveness of the disease process and the need for constant surveillance.
Rapid Autopsy Programs and Research Support: The Pre– and Post–COVID-19 Environments
Authors: Hooper Jody E. 
Published: September 2021

Abstract
Each rapid autopsy is a powerful opportunity to supply multiple researchers with many valuable tissue specimens at the same time. Since the beginning of the development of rapid autopsy, the overriding organizing principle for all rapid autopsy programs has been that the samples or organs must be removed and processed as rapidly as possible. To accomplish this, some rapid autopsy programs are focused on only 1 tumor type, whereas others accept patients demonstrating all tumor types and sometimes other diseases as well. Rapid autopsy programs are logistically complicated and labor-intensive structures; therefore, the key to their success is program flexibility and maintaining a multidisciplinary focus. The necessary collaborations in the complex relationships between clinicians and researchers can be broken down into a series of thought and action steps that must be understood, accepted, and practiced by all participants. A crucial part of the precase steps (prior to death) for a rapid autopsy is the study consenting process. It is extremely important that this individualized consent is obtained for postmortem specimens and that it is written in terms general enough to be used for patients with all types of diseases and for an appropriate range of future research uses. The advent of SARS-CoV-2/COVID-19 (severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019) has presented new challenges and opportunities to the field of autopsy pathology. Guidelines and practice had to be created and adapted to protect physicians and staff while maximizing diagnostic yield. However, any autopsy performed on a patient dying of or with COVID-19 represents a unique opportunity to contribute to understanding the disease mechanisms and to improve death certification, thus assisting in both clinical care and the development of health public policy.