bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRLS-13. NOVEL PAN-RAF INHIBITOR BELVARAFENIB AS A PROMISING TARGETED THERAPY FOR BRAF-ALTERED PEDIATRIC LOW-GRADE GLIOMAS
Authors: Gonzalez Maxine , Lebert Brittany , Campion Stephani , Aguilar-Bonilla Ana , Smith Amy 
Published: June 2023

Abstract
In recent years targeted therapy has improved the outcome of childhood cancer patients. The second most common pediatric cancers are central nervous system (CNS) tumors, particularly low-grade gliomas (LGGs). Approximately 15-20% of pediatric LGGs cases present with oncogenic mutations that alter the RAS/mitogen-activated protein kinase (MAPK) signaling pathway by the B-RAF kinase constitutive activation. Only five RAF inhibitors are FDA-approved as cancer treatments and with limited-to-no data for pediatric patients. The lack of pediatric data results from limited access to childhood clinical trials, although there has been an increase in clinical trials for RAF inhibitors and combinations for children. However, there is a pressing need for alternative therapeutic approaches for pediatric patients with BRAF-altered LGGs. Hence, this study proposes a type II pan-RAF inhibitor called Belvarafenib (BEV) as a potential therapeutic candidate. Belvarafenib has shown viability effects at 500fM to 5nM in a PRKAR2B/BRAF fusion patient-derived cell line with a calculated cytotoxic concentration 50 (CC50) of 2nM. The expression of apoptotic markers will be measured to characterize the mechanism of cell death through BEV’s direct stimulation of the MAPK signaling or via an alternative pathway. Understanding the allosteric properties of the RAF inhibitor Belvarafenib enables the opportunity to have effective and well-tolerated alternative therapies for BRAF-altered tumors in children. Thus, this preliminary study intends to profile the effectivity of Belvarafenib in cell culture and help design in vivo experiments with the potential to establish clinical trials in combination with other potential therapeutic agents.
TRLS-15. TARGETED THERAPY IN PEDIATRIC CNS TUMORS - A SINGLE INSTITUTION EXPERIENCE
Authors: Olsen Braden , Gonzalez Keishla , del Riego Angela Parra , Torres Marleni , Pabon Camila , Maher Ossama , Niazi Toba , Ragheb John , Hall Matthew , Khatib Ziad 
Published: June 2023

Abstract
Primary central nervous system malignancy treatment remains a difficult problem despite advancement in techniques. Personalized medicine is evolving in making treatment decisions and particular molecular characteristics allow new targeted therapies to be specific and effective. We retrospectively present patients with primary CNS tumors receiving targeted therapy from 2016 to the present date. Outcomes included length of therapy, time until progression of disease, and overall response. Our study includes 32 patients with malignancies such as Astrocytoma, Ganglioglioma, Glioblastoma, and Diffuse Intrinsic Pontine Glioma (DIPG), among others. Analysis was based on patients’ underlying malignancy and included variables such as identified mutations, targeted therapy, progression vs resolution of disease, and time to progression of disease after initiation of targeted therapy. Overall results show 23 patients with at least 1-year-survival. The most common targeted therapy was Trametinib, treating tumors of glial origin. 14 patients showed no progression after starting targeted therapy, the majority low grade Gliomas and Medulloblastomas. Multiple mutations were found with the most frequent being BRAF. Of our 11 patients with BRAF mutations, 8 had no progression of disease after starting Trametinib or Dabrafenib. Patients with Atypical Teratoid Rhabdoid Tumors (ATRT) were treated with either Alisertib or Alisertib/Tazemetostat and 2 out of 4, both treated with Alisertib maintenance therapy, had no disease progression after targeted therapy. Best outcomes with no disease progression were primarily Gliomas, treated with Trametinib, and Medulloblastomas, treated with Vismodegib. Of our patients with DIPG, treated with Ribociclib, average time to disease progression on targeted therapy was 4.7 months and survival rate was 33%. We have shown excellent use of targeted therapy and our analysis highlights the need for continued exploration of targeted therapy among patients with CNS tumors.
Pleiotropic Association of CACNA1C Variants With Neuropsychiatric Disorders
Authors: Wang Zuxing , Lin Xiandong , Luo Xinqun , Xiao Jun , Zhang Yong , Xu Jianying , Wang Shibin , Zhao Fen , Wang Huifen , Zheng Hangxiao , Zhang Wei , Lin Chen , Tan Zewen , Cao Liping , Wang Zhiren , Tan Yunlong , Chen Wenzhong , Cao Yuping , Guo Xiaoyun , Pittenger Christopher , Luo Xingguang 
Published: June 2023

Abstract

Background
Neuropsychiatric disorders are highly heritable and have overlapping genetic underpinnings. Single nucleotide polymorphisms (SNPs) in the gene CACNA1C have been associated with several neuropsychiatric disorders, across multiple genome-wide association studies.

Method
A total of 70,711 subjects from 37 independent cohorts with 13 different neuropsychiatric disorders were meta-analyzed to identify overlap of disorder-associated SNPs within CACNA1C. The differential expression of CACNA1C mRNA in five independent postmortem brain cohorts was examined. Finally, the associations of disease-sharing risk alleles with total intracranial volume (ICV), gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA), and average cortical thickness (TH) were tested.

Results
Eighteen SNPs within CACNA1C were nominally associated with more than one neuropsychiatric disorder (P &lt; .05); the associations shared among schizophrenia, bipolar disorder, and alcohol use disorder survived false discovery rate correction (five SNPs with P &lt; 7.3 × 10−4 and q &lt; 0.05). CACNA1C mRNA was differentially expressed in brains from individuals with schizophrenia, bipolar disorder, and Parkinson’s disease, relative to controls (three SNPs with P &lt; .01). Risk alleles shared by schizophrenia, bipolar disorder, substance dependence, and Parkinson’s disease were significantly associated with ICV, GMVs, SA, or TH (one SNP with P ≤ 7.1 × 10−3 and q &lt; 0.05).

Conclusion
Integrating multiple levels of analyses, we identified CACNA1C variants associated with multiple psychiatric disorders, and schizophrenia and bipolar disorder were most strongly implicated. CACNA1C variants may contribute to shared risk and pathophysiology in these conditions.
A longitudinal study of infant 24-hour sleep: comparisons of sleep diary and accelerometer with different algorithms
Authors: Liu Tiange , Benjamin-Neelon Sara E 
Published: June 2023

Abstract

Study Objectives
To longitudinally compare sleep/wake identification and sleep parameter estimation from sleep diaries to accelerometers using different algorithms and epoch lengths in infants.

Methods
Mothers and other caregivers from the Nurture study (southeastern United States, 2013–2018) reported infants’ 24-hour sleep in sleep diaries for 4 continuous days, while infants concurrently wore accelerometers on the left ankle at 3, 6, 9, and 12 months of age. We applied the Sadeh, Sadeh Infant, Cole, and Count-scaled algorithm to accelerometer data at 15 and 60 seconds epochs. For sleep/wake identification, we assessed agreement by calculating epoch-by-epoch percent agreement and kappas. We derived sleep parameters from sleep diaries and accelerometers separately and evaluated agreement using Bland–Altman plots. We estimated longitudinal trajectories of sleep parameters using marginal linear and Poisson regressions with generalized estimation equation estimation.

Results
Among the 477 infants, 66.2% were black and 49.5% were female. Agreement for sleep/wake identification varied by epoch length and algorithm. Relative to sleep diaries, we observed similar nighttime sleep offset, onset, and total nighttime sleep duration from accelerometers regardless of algorithm and epoch length. However, accelerometers consistently estimated about 1 less nap per day using the 15 seconds epoch, 70 and 50 minutes’ shorter nap duration per day using the 15 and 60 seconds epoch, respectively; but accelerometers estimated over 3 times more wake after nighttime sleep onset (WASO) per night. Some consistent sleep parameter trajectories from 3 to 12 months from accelerometers and sleep diaries included fewer naps and WASOs, shorter total daytime sleep, longer total nighttime sleep, and higher nighttime sleep efficiency.

Conclusions
Although there is no perfect measure of sleep in infancy, our findings suggest that a combination of accelerometer and diary may be needed to adequately measure infant sleep.
Emerging research on postacute COVID-19 complications
Authors: Williams Sydne 
Published: June 2023

ABSTRACT
An estimated 21.5% of patients in the United States who have had COVID-19 report development of a prolonged postviral syndrome that has been called postacute sequelae of COVID-19 (PASC). Symptoms can range from very mild to debilitating damage to organ systems caused directly by the virus and indirectly by the body's inflammatory response. Research into defining PASC and discovering effective treatments is ongoing. This article discusses the common presentations of PASC in patients who have had COVID-19; describes specific effects on the pulmonary, cardiovascular, and central nervous systems; and identifies potential treatments based on current literature.
Electronic Reminder to Transition Care After Hypertensive Disorders of Pregnancy
Authors: Triebwasser Jourdan E. , Lewey Jennifer , Walheim Lauren , Sehdev Harish M. , Srinivas Sindhu K. 
Published: June 2023

OBJECTIVE:
Scalable interventions are needed to improve preventive care for those with increased cardiovascular disease (CVD) risk identified during pregnancy. We hypothesized that an automated reminder message for clinicians (nudge) would increase counseling at the postpartum visit on patient transitions of care.

METHODS:
We conducted a single-center, randomized controlled trial including birthing people with a hypertensive disorder of pregnancy evaluating a nudge compared with usual care. The nudge, including counseling phrases and patient-specific information on hypertensive diagnosis, was sent to the obstetric clinician through the electronic medical record up to 7 days before the postpartum visit. The primary outcome was documentation of counseling on transitions of care to primary care or cardiology. Secondary outcomes were documentation of CVD risk, use of counseling phrases, and preventive care visit within 6 months. A sample size of 94 per group (n=188) was planned to compare the nudge intervention with usual care; given the anticipated loss to follow-up, the sample size was increased to 222. Intention-to-treat analyses were performed, with P<.05 considered significant.

RESULTS:
From February to June 2021, 392 patients were screened, and 222 were randomized and analyzed. Of these, 205 (92.3%) attended a postpartum visit. Groups were similar, but more women in the usual care group had diabetes (16.1% vs 6.7%, P=.03). After adjustment for diabetes, patients in the nudge group were more likely to have documented counseling on transitions of care (38.8% vs 26.2%, adjusted relative risk [aRR] 1.53, 95% CI 1.02–2.31), CVD risk (21.4% vs 8.4%, aRR 2.57, 95% CI 1.20–5.49), and use of aspirin in a future pregnancy (14.3% vs 1.9%, aRR 7.49, 95% CI 1.66–33.93). Counseling phrases were used more often in the nudge group (11.2% vs 0.9%, aRR 12.27, 95% CI 1.50–100.28). Preventive care visit attendance did not differ by group (22.1% vs 24.6%, aRR 0.91, 95% CI 0.57–1.47).

CONCLUSION:
A timely electronic reminder to obstetric clinicians improved counseling about transitions of care after hypertensive disorders of pregnancy but did not result in increased preventive care visit attendance.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04660032.
Plasma Lipid Analysis of Simultaneous Application of Radiofrequency Synchronized With HIFEM for Fat Reduction in Same-Day Multiple Sessions
Authors: Weiss Robert A. 
Published: June 2023

BACKGROUND
High-intensity focused electromagnetic field (HIFEM) and synchronized radiofrequency (RF) technologies have been shown to be safe and effective on multiple body parts

OBJECTIVE
To determine the plasma lipid levels and liver function tests of consecutive HIFEM + RF procedures delivered on the same day.

METHODS
Eight women and 2 men (24–59 years, BMI 22.4–30.6 kg/m2) underwent 4 30-minute consecutive HIFEM + RF procedures. The treated area differed according to gender (females: abdomen and lateral and inner thighs; males: abdomen and front and back thighs). Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyltransferase [GGT], alkaline phosphatase [ALP]) and lipid profile (cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides [TG]) was monitored from blood samples drawn before the treatment, 1 hour, 24 to 48 hours, and 1 month after treatment. The subject's satisfaction, comfort, abdominal circumference, and digital photographs were also monitored.

RESULTS
All 10 patients completed planned treatments and follow-up blood draws. No significant fluctuation or notable deviation in the measured blood parameters was observed. The average values during the study were in a range of AST 15.7 to 16.7IU/L, ALT 11.9 to 13.4IU/L, GGT 11.6 to 13.8IU/L, and ALP 71.4 to 77.2IU/L, TG 1.0 mmol/L, HDL 1.7 mmol/L, LDL 3.0 mmol/L, and cholesterol 5.0 to 5.1 mmol/L corresponded to the normal ranges. Subjects reported high comfort during the treatment and satisfaction with their results. No adverse event occurred.

CONCLUSION
Plasma levels remained stable and normal or lipids and LFTs for multiple same-day treatments of RF plus HIFEM.
Relationship between anterior capsule opening and direction of intraocular lens decentration
Authors: Nagata Mayumi , Hanemoto Tsukasa , Matsushima Hiroyuki , Senoo Tadashi 
Published: June 2023

Purpose:
To compare intraocular lens (IOL) decentration between patients in whom the continuous curvilinear capsulorhexis (CCC) completely covers the IOL optic and those in whom it incompletely covers the IOL optic and determine how an incompletely covered CCC affects the IOL position.

Setting:
Tertiary hospital in Japan.

Design:
Single-center retrospective study.

Methods:
57 eyes of 57 patients (mean age 70.8 ± 6.2 years) that underwent phacoemulsification and IOL (SN60WF) implantation in the bag between April 2010 and April 2015 were included in this study. The patients were classified based on whether the CCC completely (CC group) or incompletely (NCC group) covered the IOL optic using an anterior eye segment analysis system (EAS-1000). The IOL decentration of the groups was analyzed using EAS-1000 at 1 week, 1 month, 3 months, and 6 months postoperatively and compared. The relationship between the NCC location and the IOL direction at 3 months postoperatively was analyzed.

Results:
The NCC group (25 eyes) had a significantly higher amount of IOL decentration than the CC group (32 eyes) at 1 week, 1 month, 3 months, and 6 months postoperatively (P < .05). There was a correlation between the direction of IOL decentration and the NCC location, and IOL decentration in the NCC group occurred in the opposite direction to the NCC area.

Conclusions:
An anterior capsule opening that completely covers the IOL optic is important to control IOL decentration.
The changing face of cardiogenic shock: definitions, epidemiology, and severity assessment
Authors: Jentzer Jacob C. , Baran David A. 
Published: June 2023

Purpose of review
Cardiogenic shock (CS) has been recognized for >50 years, most commonly in the setting of myocardial infarction. This review covers recent advances in the definitions, epidemiology and severity assessment of cardiogenic shock.

Recent findings
In this review, the authors discuss the evolving definitions of cardiogenic shock, detailing the early approaches as well as more contemporary ideas. The epidemiology of CS is reviewed and then granular detail on the assessment of shock severity is provided including the role of lactate measurement and invasive hemodynamic assessment. The development of the Society for Cardiac Angiography and Intervention (SCAI) consensus statement on Classification of Cardiogenic Shock is reviewed by the principal authors. The revised SCAI Shock document is reviewed as well and the future directions for assessment of shock along with clinical applications are reviewed.

Summary
Cardiogenic shock mortality has not changed in a significant way in many years. Recent advances such as more granular assessment of shock severity have the potential to improve outcomes by allowing research to separate the patient groups which may respond differently to various therapies.
Reliability and Agreement of Automated Head Measurements From 3-Dimensional Photogrammetry in Young Children
Authors: Abdel-Alim Tareq , Tio Pauline , Kurniawan Melissa , Mathijssen Irene , Dirven Clemens , Niessen Wiro , Roshchupkin Gennady , van Veelen Marie-Lise 
Published: June 2023

This study aimed to assess the reliability and agreement of automated head measurements using 3-dimensional (3D) photogrammetry in young children. Specifically, the study evaluated the agreement between manual and automated occipitofrontal circumference (OFC) measurements (n = 264) obtained from 3D images of 188 patients diagnosed with sagittal synostosis using a novel automated method proposed in this study. In addition, the study aimed to determine the interrater and intrarater reliability of the automatically extracted OFC, cephalic index, and volume. The results of the study showed that the automated OFC measurements had an excellent agreement with manual measurements, with a very strong regression score (R
2 = 0.969) and a small mean difference of −0.1 cm (−0.2%). The limits of agreement ranged from −0.93 to 0.74 cm, falling within the reported limits of agreement for manual OFC measurements. High interrater and intrarater reliability of OFC, cephalic index, and volume measurements were also demonstrated. The proposed method for automated OFC measurements was found to be a reliable alternative to manual measurements, which may be particularly beneficial in young children who undergo 3D imaging in craniofacial centers as part of their treatment protocol and in research settings that require a reproducible and transparent pipeline for anthropometric measurements. The method has been incorporated into CraniumPy, an open-source tool for 3D image visualization, registration, and optimization, which is publicly available on GitHub (https://github.com/T-AbdelAlim/CraniumPy).
Introduction to the special issue Amphibian immunity: stress, disease and ecoimmunology
Authors: Assis Vania Regina , Robert Jacques , Titon Stefanny Christie Monteiro 
Published: June 2023

Amphibian populations have been declining worldwide, with global climate changes and infectious diseases being among the primary causes of this scenario. Infectious diseases are among the primary drivers of amphibian declines, including ranavirosis and chytridiomycosis, which have gained more attention lately. While some amphibian populations are led to extinction, others are disease-resistant. Although the host's immune system plays a major role in disease resistance, little is known about the immune mechanisms underlying amphibian disease resistance and host–pathogen interactions. As ectotherms, amphibians are directly subjected to changes in temperature and rainfall, which modulate stress-related physiology, including immunity and pathogen physiology associated with diseases. In this sense, the contexts of stress, disease and ecoimmunology are essential for a better understanding of amphibian immunity. This issue brings details about the ontogeny of the amphibian immune system, including crucial aspects of innate and adaptive immunity and how ontogeny can influence amphibian disease resistance. In addition, the papers in the issue demonstrate an integrated view of the amphibian immune system associated with the influence of stress on immune–endocrine interactions. The collective body of research presented herein can provide valuable insights into the mechanisms underlying disease outcomes in natural populations, particularly in the context of changing environmental conditions. These findings may ultimately enhance our ability to forecast effective conservation strategies for amphibian populations.
This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
Contrasting effects of transdermal and implant corticosterone treatments in the American bullfrog wound healing
Authors: Madelaire Carla B. , Silva Diego P. , Titon Stefanny C. M. , Lamadrid-Feris Faride , Floreste Felipe R. , Titon Jr Braz , Gomes Fernando R. 
Published: June 2023

Glucocorticoid (GC) release is triggered by adverse stimuli that activate the hypothalamus-pituitary-adrenal/interrenal axis. Glucocorticoids may enhance or suppress immune functions depending on the level of elevation. In this study, we investigated the effects of transient and chronic increase of corticosterone (CORT) on the wound healing of the American bullfrog. Frogs were submitted to a daily transdermal hormonal application that acutely elevated CORT plasma levels, or vehicle as a control. Other frogs were surgically implanted with a silastic tube filled with CORT that resulted in chronic elevation of CORT plasma levels or received empty implants as a control. A dermal biopsy was performed to create a wound and was photographed every 3 days. Individuals treated with transdermal CORT started healing faster than their control 32 days after the biopsy. Frogs that received CORT implants tended to heal slower than control subjects. Plasma bacterial killing ability was not affected by treatment, which reinforces the constitutive nature of this innate immune trait. By the end of the experiment, frogs from the acute CORT treatment had smaller wounds compared with those receiving the CORT-filled implants, highlighting the differential effects of acute (immunoenhancing) and chronic (immunosuppressive) elevation of CORT plasma levels.
This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">FEBRILE SEPSIS:&#160; FIRST REPORT OF HUMAN DISEASE DUE TO <em>PAENIBACILLUS SILVAE</em>
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Authors: BENEDETTI PAOLO , Vecchia Ilaria Dalla , Fasan Daniele , Pegoraro Manuela 
Published: June 2023

ABSTRACT
Introduction. Paenibacillus species are saprophytes widely distributed in nature and rarely associated with overt human infection. Most of cases have been described in people with important comorbidities and/or immunodepression. We report here what is, to the best of our knowledge, the first documented case of human disease due to P. silvae, so far considered an exclusively environmental micro-organism.
Case presentation. A 57-year-old female patient was referred to our Unit after a 2-month history of remittent fever. Upon admission, septic state and bacteraemia was revealed; P. sylvae was speciated by 16S-rRNA gene amplification and sequencing MALDI-TOF. The patient became afebrile after 9 days of antibiotic treatment and was completely cured after a 2-week regimen with I.V. amoxicillin-clavulanate plus oral doxycycline.
Conclusion. The patient did not report any episode of infection occurred previously. Most of the well-known risk factors to Paenibacillus bacteraemia, i.e., invasive procedures, use of intravenous drugs, and foreign bodies could be revealed, although her immune system was probably impaired due to obesity and heavy smoking. We suggest that the isolation of bacteria belonging to the Paenibacillus genus should not be disregarded, since there is accumulating evidence that these organisms may cause disease even in immunocompetent subjects.