bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAFV600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database
Authors: Cohen Romain , Liu Heshan , Fiskum Jack , Adams Richard , Chibaudel Benoist , Maughan Timothy S , Van Cutsem Eric , Venook Alan , Douillard Jean-Yves , Heinemann Volker , Ja Punt Cornelis , Falcone Alfredo , Bokemeyer Carsten , Kaplan Richard , Lenz Heinz-Josef , Koopman Miriam , Yoshino Takayuki , Zalcberg John , Grothey Alex , de Gramont Aimery , Shi Qian , André Thierry 
Published: March 2021

AbstractBackgroundFirst-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAFmt on the efficacy of targeted therapies with first-line chemotherapy.MethodsIndividual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Outcomes were compared between treatment groups that were concurrently randomly assigned whenever possible.ResultsA total of 6391 patients from 10 RCTs were included: 573 BRAFmt (9.0%), 2059 KRASmt (32.2%), and 3759 double wild type (58.8%). BRAFmt mCRC patients experienced statistically significantly poorer OS than those with KRASmt (adjusted hazard ratio [HRadj] = 1.46, 95% confidence interval [CI] = 1.30 to 1.64) and patients with double wild-type tumors (HRadj = 2.14, 95% CI = 1.94 to 2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy with or without anti-epidermal growth factor receptor (anti-EGFR) (HRadj = 0.96, 95% CI = 0.71 to 1.30; and HRadj = 0.85, 95% CI = 0.66 to 1.14, respectively).ConclusionsOur data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients.
All Hands on Deck: Addressing Adolescent Depression in Pediatric Primary Care
Authors: Kenny Jessica , Costello Lisa , Kelsay Kim , Bunik Maya , Xiong Shengh , Chiaravalloti Lauren , Millar Amanda , Talmi Ayelet 
Published: March 2021

Abstract

Objective
This study examines prevalence rates of elevated depression symptoms utilizing the Patient Health Questionnaire-9 Item Modified for Adolescents (PHQ-9A), characterizes recommendations and interventions by primary care providers (PCPs) and behavioral health clinicians (BHCs) in response to elevated PHQ-9As, and identifies factors associated with improved PHQ-9A scores at follow-up pediatric primary care visits.

Methods
A mixed methods approach was taken. Visit data, demographics, and PHQ-9A scores for 2,107 adolescents aged 11–18 were extracted using clinical informatics between January 3, 2017 and August 31, 2018. Descriptive statistics and chi-square analyses were conducted, followed by conventional content analysis of electronic medical records to examine qualitative results. Qualitative analyses were transformed into quantitative results and analyzed using point biserial correlations.

Results
Of the 2,107 adolescents, 277 (13%) had an elevated PHQ-9A. Content analysis resulted in 40 actions (17 PCP codes, 23 BHC codes) in response to an elevated PHQ-9A. Significant correlations were found between an improved PHQ-9A at a follow-up visit and the PCP referring to integrated behavioral health (r = .20, p &lt; .01), and BHCs recommending and checking in at a follow-up visit (r = .20, p &lt; .05), conducting a risk assessment (r = .15, p &lt; .05), and providing psychoeducation about mood symptoms (r = .15, p &lt; .05).

Conclusions
Primary care is an ideal setting to address the public health crisis of untreated adolescent depression. Implications for screening processes, practice implications for PCPs and BHCs, future directions, and limitations are discussed.
Scale-dependent anisotropy of electric field fluctuations in solar wind turbulence
Authors: Deepali Deepali , Banerjee Supratik 
Published: March 2021

ABSTRACT
We study the variation of average powers and spectral indices of electric field fluctuations with respect to the angle between average flow direction and the mean magnetic field in solar wind turbulence. Cluster spacecraft data from the years 2002 and 2007 are used for the present analysis. We perform a scale-dependent study with respect to the local mean magnetic field using wavelet analysis technique. Prominent anisotropies are found for both the spectral index and power levels of the electric power spectra. Similar to the magnetic field fluctuations, the parallel (or antiparallel) electric fluctuation spectrum is found to be steeper than the perpendicular spectrum. However, the parallel (or antiparallel) electric power is found to be greater than the perpendicular one. Below 0.1 Hz, the slope of the parallel electric power spectra deviates substantially from that of the total magnetic power spectra, supporting the existence of Alfvénic turbulence.
Can’t Work From Home: Pooled Nucleic Acid Testing of Laboratory Workers During the COVID-19 Pandemic
Authors: Rawlings Stephen A , Scott Brianna , Layman Laura , Naranatt Pramod , Heltsley Roy , Ignacio Caroline , Porrachia Magali , Gianella Sara , Smith Davey , Chaillon Antoine 
Published: March 2021

Abstract
Together with protective measures, routine screening for severe acute respiratory syndrome coronavirus 2 infection helps provide a safe working environment. We evaluated a pooled nucleic acid testing strategy in a research laboratory. It allowed lab activity to be maintained and would save 25 920 person-hours and $1 684 800/year by increasing the margin of safety for returning to work.
Transpalpebral Superolateral Orbitotomy for Orbital Cavernous Hemangioma Extirpation: 2-Dimensional Operative Video
Authors: May Adrien T , Guatta Ramona , Meling Torstein R 
Published: March 2021

Abstract
Cavernous hemangiomas of the orbit are low-pressure vascular tumors. Usually benign, they become symptomatic by the local mass effect, pushing the eyeball forward, causing exophthalmia, by oculomotor muscle and nerve compression causing diplopia or by optic nerve compression, leading to visual impairment.
Radiotherapy is of limited value in their treatment because of the fragility of the optic nerve and subsequent blindness risk. Surgery remains the gold standard and definitive treatment. We illustrate in this video a transpalpebral superolateral orbitotomy and extirpation of an orbital cavernous hemangioma.
A 52-yr-old healthy woman was sent for neurosurgical consultation by her ophthalmologist. She described a history of progressive unilateral right exophthalmia in the last months. A cerebral magnetic resonance imaging (MRI) revealed a 2.5-cm-large orbital lesion located superiorly and laterally to the eyeball. Surgery was proposed and accepted by the patient. The frontozygomatic component of the orbital rim needed to be removed to safely extirpate the cavernous hemangioma without exerting unnecessary and risky pressure on the eyeball.
1,2
We decided to go for a superolateral orbitotomy via a transpalpebral incision.
3
Total removal of the lesion was achieved with no complication. Exophthalmia normalized.
Written patient consent was obtained for use and publication of their image after complete information. The patient consented to the surgery.
Microvascular Transposition Without Teflon: A Single Institution's 17-Year Experience Treating Trigeminal Neuralgia
Authors: Pines Andrew R , Butterfield Richard J , Turcotte Evelyn L , Garcia Jose O , De Lucia Noel , Algier Emily J , Patel Naresh P , Zimmerman Richard S 
Published: March 2021

Abstract

BACKGROUND
Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence.

OBJECTIVE
To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon.

METHODS
Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence.

RESULTS
A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23).

CONCLUSION
Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.
Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia are more frequent in advanced versus early Parkinson’s disease
Authors: Sringean Jirada , Stefani Ambra , Marini Kathrin , Bergmann Melanie , Werkmann Mario , Holzknecht Evi , De Marzi Roberto , Brandauer Elisabeth , Hackner Heinz , Djamshidian Atbin , Stockner Heike , Gaig Carles , Iranzo Alex , Santamaria Joan , Tolosa Eduardo , Seppi Klaus , Poewe Werner , Högl Birgit 
Published: March 2021

Abstract

Study Objectives
To evaluate macro sleep architecture and characterize rapid eye movement (REM) sleep without atonia (RWA) by using the SINBAR excessive electromyographic (EMG) montage including mentalis and upper extremity muscles in early and advanced Parkinson’s disease (PD).

Methods
We recruited 30 patients with early- and advanced-stage of PD according to Movement Disorder Society (MDS) Clinical Diagnostic Criteria. Participants were classified as early-stage PD if they were treatment-naïve or had no motor complications and had been diagnosed with PD within the previous 6 years. Advanced PD was defined as a disease duration equal to or &gt;6 years with or without motor complications.

Results
There was significantly shorter REM sleep latency in early as compared to the advanced stage of PD. We found that the sleep Innsbruck Barcelona (SINBAR) EMG index and tonic EMG activity of the mentalis muscle in advanced-stage PD were significantly higher than in early-stage PD with a trend in phasic EMG activity of the flexor digitorum superficialis muscles. The SINBAR EMG index, tonic and any EMG activity of the mentalis muscle, and phasic EMG activity of flexor digitorum superficialis muscles significantly correlated with disease duration.

Conclusions
This study analyzed RWA using the SINBAR EMG montage in early- and advanced-stage of PD and showed higher RWA in mentalis and flexor digitorum superficialis muscles and SINBAR EMG index in advanced-PD patients compared to patients in the early stage. Also, polysomnography-confirmed REM sleep behavior disorder was more common in advanced versus early-stage patients. Our findings suggest that RWA worsens or is more intense or more frequent with disease progression.
Manipulation of rapid eye movement sleep via orexin and GABAA receptor modulators differentially affects fear extinction in mice: effect of stable versus disrupted circadian rhythm
Authors: Clark Jacob W , Daykin Heather , Metha Jeremy A , Allocca Giancarlo , Hoyer Daniel , Drummond Sean P A , Jacobson Laura H 
Published: March 2021

Abstract
Sleep disruption, and especially rapid eye movement (REM) sleep disruption, is associated with fear inhibition impairment in animals and humans. The REM sleep-fear inhibition relationship raises concern for individuals with posttraumatic stress disorder (PTSD), whose sleep disturbance is commonly treated with hypnotics that disrupt and/or decrease REM sleep, such as benzodiazepines or “Z-drugs.” Here, we examined the effects of the Z-drug zolpidem, a gamma-aminobutyric acidA (GABAA) receptor positive allosteric modulator, as well as suvorexant, an orexin receptor antagonist (hypnotics which decrease and increase REM sleep, respectively) in the context of circadian disruption in murine models of fear inhibition-related processes (i.e. fear extinction and safety learning). Adult male C57Bl/6J mice completed fear and safety conditioning before undergoing shifts in the light–dark (LD) cycle or maintaining a consistent LD schedule. Fear extinction and recall of conditioned safety were thereafter tested daily. Immediately prior to the onset of the light phase between testing sessions, mice were treated with zolpidem, suvorexant, or vehicle (methylcellulose). Polysomnographic analyses showed the temporal distribution of REM sleep was misaligned during LD cycle-shifts, while REM sleep duration was preserved. Suvorexant increased REM sleep and improved fear extinction rate, relative to zolpidem, which decreased REM sleep. Survival analysis demonstrated LD shifted mice treated with suvorexant were faster to achieve complete extinction than vehicle and zolpidem-treated mice in the LD shifted condition. By contrast, retention of conditioned safety memory was not influenced by either treatment. This study thus provides preclinical evidence for the potential clinical utility of hypnotics which increase REM sleep for fear extinction after PTSD-relevant sleep disturbance.
Expansion of Internal Hyphal Growth in Fusarium Head Blight–Infected Grains Contributes to the Elevated Mycotoxin Production During the Malting Process
Authors: Jin Zhao , Solanki Shyam , Ameen Gazala , Gross Thomas , Poudel Roshan Sharma , Borowicz Pawel , Brueggeman Robert S. , Schwarz Paul 
Published: March 2021

Fusarium head blight (FHB) and the occurrence of mycotoxins is the largest food safety threat to malting and brewing grains. Worldwide surveys of commercial beers have reported that the trichothecene mycotoxin deoxynivalenol (DON) is the most frequent contaminant in beer. Although the DON content of grain generally declines during steeping due to its solubilization, Fusarium spp. can continue to grow and produce DON from steeping through the early kilning stage of malting. DON present on malt is largely extracted into beer. The objective of the current study was to localize the growth of Fusarium spp. within FHB-infected kernels by developing an improved method and to associate fungal growth with the production of DON during malting. FHB-infected barley, wheat, rye, and triticale grains that exhibited large increases in the amount of Fusarium Tri5 DNA and trichothecene mycotoxins following malting were screened for hyphal localization. The growth of fungal hyphae associated with grain and malt was imaged by scanning electron microscopy and confocal laser-scanning microscopy assisted with WGA-Alexa Fluor 488 staining, respectively. In barley, hyphae were present on or within the husk, vascular bundle, and pericarp cavities. Following malting, vast hyphal growth was observed not only in these regions but also in the aleurone layer, endosperm, and embryo. Extensive fungal growth was also observed following malting of wheat, rye, and triticale. However, these grains already had an extensive internal presence of Fusarium hyphae in the unmalted grain, thus representing an enhanced chance of fungal expansion during the malting. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Methionine Deprivation Induced Effects on the Growth of PC3 prostate cancer cells
Authors: Diaz Eduardo , Nosal Rebecca , Venkatachalam KV 
Published: March 2021

Methionine is a key nutrient required for the synthesis of S‐adenosylmethionine (SAM). SAM is the universal methyl group donor. Methionine gamma lyase deaminase (Mgld) is an enzyme that degrades methionine into alpha‐ketobutyrate and methylthiol. In this study, the Mgld gene was cloned into vectors that expressed Mgld, either in the cytosol or in the nucleus. The prostate cancer cell line, PC3 (ATCC‐CRL1435) was transfected with vectors containing Mgld. The PC3 cells experience cell death when Mgld is expressed in the cytosol or nucleus. In the presence of Proparglycine (PGLY), a Mgld inhibitor, the cells proliferate to a moderate degree. Co‐treatment of the PGLY with the nuclear Mgld caused a slight decrease of cells whereas with cytoplasmic Mgld caused a slight increase. In the cytoplasm, methionine is required for forming cysteine; cysteine in turn is required for glutathione (cells redox agent). Both cysteine and methionine are required for protein synthesis. Therefore, cytosolic dwindling of methionine will hamper protein synthesis and it should, in general, affect the growth of Mgld treated cells when compared to controlled cells. The addition of PGLY alone or in combination with the cytosolic vector increased proliferation, while the addition of PGLY to the nuclear vector caused modest cell death. We conclude that the methylation status of PC3 might be different and it affects the growth in varying degrees depending on the location of the Mgld expression. We speculate that PGLY might affect expressed Mgld and endogenous cytosolic cystathione beta‐synthase activity, resulting in complex cell fate, a hypothesis that needs to be tested further.Support or Funding InformationNSU Internal grantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐thrombotic and Anti‐inflammatory Nanoparticle Limits Early Remodeling in Acute Myocardial Infarction
Authors: Grabau Ryan , Chen Junjie , Weinheimer Carla , Kovacs Attila , Pan Hua , Wickline Samuel A. 
Published: March 2021

Acute myocardial infarction (AMI) is a life‐threatening medical condition. Based on the statistics updated in 2017, there is a person experiencing myocardial infarction every 40 seconds. For AMI patients, majority of them miss the treatment window for rescuing significant amounts of viable myocardium. However, infarction size can expand for weeks after the initial AMI, which provides an opportunity to prevent ventricular remodeling (progressive chamber enlargement) as well as improve healing process. AMI associated secondary ischemia further induces endothelial damage, elevated propagulation status, inflammation, and extracellular collagen degradation. Accordingly, the objective of this study is to reduce early ventricular remodeling by preventing microvascular thrombosis and reducing inflammation simultaneously with PPACK (phenylalanine‐proline‐arginine chloromethylketone) perfluorocarbon (PFC) nanoparticles (NP). Benefits of delivery PPACK by PFC NP are 1) enabling formation of anticoagulation surface specifically in the damaged vessels where thrombin is activated in order to preserve vascular integrity and limit inflammation induced by thrombin signaling and 2) minimum systemic exposure to avoid the risk of bleeding. Fluorescence microscopic images demonstrated the delivery of PFC NPs to the area at risk and remain there 24 hours after the i.v. injection (n=10) (Fig. A). For all 32 mice underwent closed‐chest ischemia (LAD occlusion) for 90 min followed by 24 hrs reperfusion. Before and 24 hrs after ischemic reperfusion injury, echocardiography was performed (VEVO 2200). The results (Fig. B) demonstrated that PPACK NP treated mice exhibited marked preservation of cardiac functional parameters as early as 24 hours after ischemia as compared to control mice according to changes in contractile metrics: 1) ΔEDV%: 40%±21% vs 77%±38% for treated vs control (p=0.02) and 2) ΔESV%: 118%±43% vs 216%±108%, for treated vs control (p=0.02) (n=16/group). To better understand the therapeutic mechanism, transcriptome profile has been evaluated by using RNASeq on normal zones and border zones of AMI mice with (n=5) or without (n=4) PPACK PFC NP treatment. The results demonstrated that in the border zone after 24 hours reperfusion, PPACK PFC NP treatment attenuated inflammatory NF‐kB signaling, and reduced NF‐kB dependent proteases (MMP 8, 9, 25), which were ~2 times higher in control group (Fig C). Moreover, numerous collagen transcripts, including Col1, 5, 6, 11, 16, and 24, were significantly elevated in the treatment group (Fig D), offering protective effects in AMI. These results demonstrate that PPACK PFC nanoparticle treatment may enhance healing in AMI and preserve cardiac microarchitecture.Support or Funding InformationR01 DK102691R01 AR067491R01 HL073646‐08This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characteristics of Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Comparison With Influenza in Children Admitted to U.K. PICUs
Authors: Kanthimathinathan Hari Krishnan , Buckley Hannah , Lamming Caroline , Davis Peter , Ramnarayan Padmanabhan , Feltbower Richard , Draper Elizabeth S. 
Published: March 2021

Objectives:
Severe acute respiratory syndrome coronavirus-2 affects adults disproportionately more than children. A small proportion of children with severe acute respiratory syndrome coronavirus-2 required admission to a PICU. We describe the nationwide U.K. PICU experience of severe acute respiratory syndrome coronavirus-2 infection during the first wave of the pandemic and compare this with the critical care course of the 2019 influenza cohort.

Design:
Prospective nationwide cohort study of characteristics of severe acute respiratory syndrome coronavirus-2–positive children. Data collection utilized routine Pediatric Intensive Care Audit Network and severe acute respiratory syndrome coronavirus-2–specific data.

Setting:
All U.K. PICUs.

Patients:
Children less than 18 years old, admitted to U.K. PICUs between March 14, 2020, and June 13, 2020, and a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction. Children admitted to U.K. PICUs in 2019 with influenza provided comparison.

Interventions:
None.

Measurements and Main Results:
We identified 76 PICU admissions among 73 children with a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test. Prevalence of PICU admissions per million was 5.2 for children versus 260 for adults. Ten children (14%) were identified on routine screening. Seventeen children (23%) had pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Seventeen (23%) had coinfections. Invasive ventilation was required in seven of 17 children (41%) with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 versus 38 of 56 other severe acute respiratory syndrome coronavirus-2 positive children (68%), with 77% requiring vasoactive support versus 43%, respectively. Seven children (10%) died. In comparison with influenza children, severe acute respiratory syndrome coronavirus-2 children were older (median [interquartile range]: 10 [1–13] vs 3 yr [1–8 yr]), more often Black or Asian (52% v 18%), higher weight z score (0.29 [–0.80 to 1.62] vs –0.41 [–1.37 to 0.63]), and higher deprivation index (3.3 [–1 to 6.3] vs 1.2 [–1.8 to 4.4]). Comorbidities, frequency of organ supports, and length of stay were similar.

Conclusions:
This nationwide study confirms that PICU admissions with severe acute respiratory syndrome coronavirus-2 infections were infrequent. We have reported similarities and differences in sociodemographic characteristics, organ support interventions, and outcomes of children affected by severe acute respiratory syndrome coronavirus-2 compared with influenza.