bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLTI-02. Impact of driver mutations on timing, pattern, treatment, and outcome in patients with brain metastases from non-small cell lung cancer
Authors: Jünger Stephanie , Eich Marie-Lisa , Meissner Anna-Katharina , Ruge Maximilian , Goldbrunner Roland , Grau Stefan 
Published: August 2021

Abstract

Objective
To assess the impact of driver mutations in non-small cell lung cancer (NSCLC) on the formation and treatment outcome of brain metastases (BM).

Patients and methods
We retrospectively analyzed patients with BM from NSCLC with respect to driver mutations and assessed timing and pattern of BM development as well as local cerebral control and survival after BM treatment.

Results
We included 253 patients. Histology was adenocarcinoma in 223, squamous cell carcinoma in 25 and not otherwise specified (NOS) in five patients. All tumors were analyzed for known alterations in NSCLC by panel sequencing and fluorescence in situ hybridization (FISH). An activating KRAS mutation (n=85) was the most prevalent mutation, followed by activating EGFR mutation (n=31) and MET amplification (n=29). Other mutations were detected in 27 patients. No alterations were found in 102 patients. Time to BM development did not differ between the molecular groups (p=.22), nor did the number (p=.72) or location (supra- vs. infratentorial; p=.76) of the BM. Patients underwent multimodal cerebral treatment comprising surgery followed by radiotherapy and/or stereotactic radiosurgery (n=138), whole brain radiotherapy (n=13) or stereotactic radiosurgery alone (n=102). Systemic treatment was initiated or continued after BM therapy in 169 patients and its frequency did not differ significantly between genotypes (p=.08) while the modality of medical treatment depended on genotype (p&lt;0.0001). The latter showed longer local cerebral control rates compared to other mutations (0.23) and a longer overall survival compared to KRAS and wild type genotypes (p=.015). Systemic treatment (HR 2.1 95%CI 1.4–3.0; p&lt;.0001) and a good clinical status (HR 2.1 95%CI 1.2–3.7; p=0.014) were the only independent factors for further survival.

Conclusion
The actual known driver mutations do not influence BM formation. Specific genotypes show a better oncological course, presumably due to available molecular treatment.
OTHR-03. Brain Metastasis Among Ovarian Cancer Patients
Authors: Limon Dror , Shachar Eliya , Adar Lyri , Hasson Shira Peleg , Safra Tamar 
Published: August 2021

Abstract

Background
Brain metastasis (BM) are uncommon among ovarian cancer (OC) patients. Their frequency, risk factors and clinical repercussions are not well described. We assessed OC patients who developed BM, the role of BRCA status and survival implications.

Methods
Study cohort included OC patients treated at our center, from 2002–2020. We retrospectively evaluated clinical parameters, risk for BM development and association with survival data.

Results
Among 972 OC patients, 28 (2.9%) were diagnosed with BM. Comparing the BM to non-BM group, median age of 60 across both groups, stage III-IV at diagnosis was more common among BM group (96.4% vs. 84.8%, p=0.0065) while platinum sensitivity was similar (92.3% in BM vs. 80.8% in non-BM, p=0.2193). Out of 658 patients tested for BRCA, 33.6% (n=221) were BRCA mutation carriers (BRCA+). Of the patients with BM, 22 tested for BRCA, 13 were carriers. BRCA+ was significantly higher in the BM group compared to the non-BM group (59.1% vs. 32.9%, p=0.0123). Among BRCA+ the rate of BM was higher than among BRCA- (5.8% vs. 2.1%, p=0.0123, HR=3.029; 95%CI: 1.4–6.5). Median time from OC diagnosis to BM and from disease recurrence to BM, was longer for BRCA+ compared to BRCA- (44.3mo vs. 32.3mo and 11.8mo vs. 0.7mo, respectively). Median survival (mOS) was not significantly different among patients with BM compared to those without BM (59.4mo vs. 71.2mo, p=0.36). Following diagnosis of BM, mOS was 20.6mo among BRCA+ and 12.3mo among BRCA- (p=0.4266). No correlation was demonstrated with PARP inhibitors or bevacizumab treatment and subsequent development of BM.

Conclusion
BM are an infrequent event among OC patients. However, the risk is three-folds higher among BRCA+. Interestingly, BM do not significantly alter survival among OC patients. Our work suggests that the higher rate of BM in BRCA+ may be related to longer survival. Another hypothesis requiring further evaluation, is possible higher brain tropism among this population.
OTHR-13. IMPACT the brain: improving metastatic breast cancer patient access to coordinated treatment
Authors: Grogan Nicole , Pierce-Gjeldum Donna , Swartz Leigh , Verbal Kait , Merajver Sofia , Friese Christopher , Kiyota Ayano , Heth Jason , Leung Denise , Smith Sean , Gabel Nicolette , Kim Michelle , Morikawa Aki 
Published: August 2021

Abstract
Central nervous system (CNS) metastases are associated with decreased survival and quality of life for patients with metastatic breast cancer (MBC). Multi-disciplinary care can optimize outcomes. This project aims to improve access to coordinated care for patients with MBC and CNS metastases.
Patients with MBC and CNS metastases are referred and offered to enroll in our care coordination program. A team consisting of specialists (breast medical oncology, breast cancer genetics, radiation oncology, neurosurgery, neuro-oncology, physical medicine and rehabilitation (PM&R), neuropsychology, and palliative care) supports a dedicated program coordinator who provides navigation, education, specialty referral, and clinical trial screening. A unique intake form developed for the program creates personalized, coordinated, and expedited referrals. Patient-reported outcomes and caregiver burden assessments are collected.
Since May 2020, 43 patients were referred and a total of 40 patients (93%) were enrolled – 2 (5%) declined due to perceived burden of participation and 1 (2%) died before enrollment. 85% of patients were Caucasian (n = 34) and 15% were non-Caucasian (n=6). Median time to program intake was 1 day (range: 0–8 days). Of the 43 patients referred, 17 (40%) consented to research studies in the metastatic setting. 11 were for an interventional trial (65%), while 9 consents were for non-interventional studies (53%). In addition to the initially referred specialty, 56 referrals were made across 7 sub-specialties; 37 patients (66%) were subsequently seen by a sub-specialist, most commonly radiation oncology (n = 9), neuro-oncology (n=8), PM&R (n=8), and neuropsychology (n=8).
Implementation of a care coordination program for patients with MBC and CNS metastases is feasible. Further, it allows for improved access to care across sub-specialties and supports participation in clinical research for a group of cancer patients historically underrepresented in research studies.
Funding: National Comprehensive Cancer Network Oncology Research Program from financial support provided by Pfizer.
Effect of brown seaweed on plasma glucose in healthy, at-risk, and type 2 diabetic individuals: systematic review and meta-analysis
Authors: Vaughan Kate , Ranawana Viren , Cooper David , Aceves-Martins Magaly 
Published: August 2021

AbstractContextSustained hyperglycemia triggers chronic disease, including type 2 diabetes. A considerable volume of research has explored the effects of brown seaweed on plasma glucose control, but equivocal findings have been reported.ObjectiveA systematic review and meta-analysis was conducted to assess the evidence from human randomized controlled trials (RCTs) on the effects of brown seaweed on plasma glucose in healthy, at-risk, and individuals with type 2 diabetes.Data SourcesMEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for reports published between 2000 and 2020.Data ExtractionPopulation, intervention, comparator, outcome, and study design data were extracted.Data AnalysisEighteen RCTs met our inclusion criteria. The reported results varied across and between populations. Meta-analyses showed a significant effect, favoring the intervention group for both fasting (mean difference –4.6 [95% CI –7.88, –1.33]) and postprandial (mean difference –7.1 [95% CI –7.4, –6.9]) plasma glucose.ConclusionBrown seaweed and its extracts show potential for preventing and managing hyperglycemia. Our meta-analysis confirms that brown seaweed positively affects plasma glucose homeostasis, with particularly promising postprandial plasma glucose effects. However, further research is needed because no high-quality RCT was identified. Species-specific and dose–response research is also required.Systematic Review RegistrationPROSPERO registration no. CRD42020187849.
Data-driven dynamics of phytoplankton blooms in a reaction–diffusion NPZ model
Authors: Cowall Seth T , Oliver Matthew J , Cook L Pamela 
Published: August 2021

Abstract
The causes of seasonal phytoplankton blooms in the ocean are a debated topic. The disturbance-recovery hypothesis posits that blooms are initiated when seasonally changing light and mixing conditions disrupt attractive equilibrium states in the predator–prey relationship between zooplankton and phytoplankton, leading to an accumulation in phytoplankton biomass. This paper follows up on this notion with a nutrient-phytoplankton-zooplankton (NPZ) model incorporating diffusion and depth-dependent coefficients in which we explore the nature of these attractive states. The reaction–diffusion NPZ model, incorporated with seasonal solar radiation and mixed layer depth data, simulates blooms with better timing than a related ordinary differential equations model but still leaves room for further modeling and improvement. The results of the data-driven, reaction–diffusion model aid in understanding the driving forces of the simulated phytoplankton blooms. The results also reveal a significant influence on the vertical structure of plankton concentration by the attenuation of light with depth in the ocean. Models that accurately simulate blooms tend to share characteristics of the reaction–diffusion model in this paper. The dynamics described in this paper could be a key mechanism that seasonally disrupts the ecological balance between phytoplankton and zooplankton and facilitates a high-latitude marine phytoplankton bloom.
Error-Manipulation Gait Training for Veterans With Nontraumatic Lower Limb Amputation: A Randomized Controlled Trial Protocol
Authors: Kline Paul W , So Noel , Fields Thomas , Juarez-Colunga Elizabeth , Christiansen Cory L 
Published: August 2021

Abstract

Objective
he purpose of this study will be to determine the efficacy of error-manipulation gait training (error-augmentation or error-correction) to improve step length symmetry and secondary health outcomes in veterans with unilateral nontraumatic transtibial amputation (TTA).

Methods
This will be a 3-arm, parallel, assessor-blinded, randomized controlled trial, with baseline, postintervention, and 3-month follow-up assessments in a VA Geriatric Research Education and Clinical Center. Participants are 54 US military veterans ranging in age from 50 to 85 years with a unilateral transtibial nontraumatic amputation. Participants will be randomized into 1 of 3 groups: error-augmentation training (EAT), error-correction training (ECT), or supervised walking (CTL). Each group will complete 8 split-belt treadmill walking training sessions of 25 minutes each over 4 weeks. The EAT group will walk with belts moving at asymmetrical speeds. The ECT group will walk to the cadence of a metronome and the split belts moving at symmetrical speeds. The CTL group will walk with symmetrical belt speeds and without feedback. Step length symmetry is the primary outcome and will be assessed using an asymmetry index during overground walking. Secondary outcomes include lower extremity joint work during treadmill walking, 6-Minute Walk Test performance, daily step count, participant-perceived disability, and residual-limb integumentary health. Outcomes will be assessed at preintervention, 1-week postintervention (primary endpoint), and 13 weeks postintervention.

Impact
This study protocol focuses on an understudied area of rehabilitation for patients with nontraumatic unilateral TTA who have high levels of spatiotemporal gait asymmetry and mobility impairment. The results of this study will inform future implementation of clinical gait training interventions to improve spatiotemporal gait symmetry and long-term health and disability outcomes in patients with nontraumatic unilateral TTA.
Redefining public health and sustainable economy: Covid-19 from pandemic to endemic
Authors: Deguma Jabin J , Capuno Reylan G , Manguilimotan Ramil P , Padillo Gengen G , Deguma Melona C 
Published: August 2021

Abstract
With the recent claim that the maintenance of population immunity will not depend on continued vaccinations but on the endemic presence of the virus, the proper understanding of the value of public health allows us to configure human living conditions as it thrives in a world where the novel Corona Virus Disease in 2019 (Covid-19) becomes endemic. World leaders and economic managers need to redefine public health not just as a means that enables economic productivity but as a substantially primordial goal—an end that every functional society must achieve via living an economically sustainable lifestyle. This paper argues that economic and societal sustainability thus must be framed and delimited within the human ecological boundary—a crucial viewpoint that could sustain public health amid a Covid-19 endemic world while preventing another viral pandemic from occurring.
TCF19 and p53 regulate transcription of TIGAR and SCO2 in HCC for mitochondrial energy metabolism and stress adaptation
Authors: Mondal Payel , Gadad Shrikanth S. , Adhikari Swagata , Ramos Enrique I. , Sen Sabyasachi , Prasad Parash , Das Chandrima 
Published: August 2021

AbstractAlteration in glucose homeostasis during cancer metabolism is an important phenomenon. Though several important transcription factors have been well studied in the context of the regulation of metabolic gene expression, the role of epigenetic readers in this regard remains still elusive. Epigenetic reader protein transcription factor 19 (TCF19) has been recently identified as a novel glucose and insulin‐responsive factor that modulates histone posttranslational modifications to regulate glucose homeostasis in hepatocytes. Here we report that TCF19 interacts with a non‐histone, well‐known tumor suppressor protein 53 (p53) and co‐regulates a wide array of metabolic genes. Among these, the p53‐responsive carbohydrate metabolic genes Tp53‐induced glycolysis and apoptosis regulator (TIGAR) and Cytochrome C Oxidase assembly protein 2 (SCO2), which are the key regulators of glycolysis and oxidative phosphorylation respectively, are under direct regulation of TCF19. Remarkably, TCF19 can form different transcription activation/repression complexes which show substantial overlap with that of p53, depending on glucose‐mediated variant stress situations as obtained from IP/MS studies. Interestingly, we observed that TCF19/p53 complexes either have CBP or HDAC1 to epigenetically program the expression of TIGAR and SCO2 genes depending on short‐term high glucose or prolonged high glucose conditions. TCF19 or p53 knockdown significantly altered the cellular lactate production and led to increased extracellular acidification rate. Similarly, OCR and cellular ATP production were reduced and mitochondrial membrane potential was compromised upon depletion of TCF19 or p53. Subsequently, through RNA‐Seq analysis from patients with hepatocellular carcinoma, we observed that TCF19/p53‐mediated metabolic regulation is fundamental for sustenance of cancer cells. Together the study proposes that TCF19/p53 complexes can regulate metabolic gene expression programs responsible for mitochondrial energy homeostasis and stress adaptation.
Professional Values Development Among Jordanian Baccalaureate Nursing Students
Authors: Subih Maha , Al Hadid Lourance , Al Omari Domam , Albana Haya , Shahrour Loai Abu 
Published: August 2021

Abstract

AIM
The aims of the study were to identify professional values among third- and fourth-year baccalaureate nursing students at private and public universities in Jordan and to investigate the demographic variables correlating with professional values.

BACKGROUND
Educational curricula reinforce professional values among nursing students.

METHOD
A cross-sectional design was used; the questionnaire included a demographic variable survey and the Nurses Professional Values Scale-3.

RESULTS
The mean score for the overall value scale was moderate (3.5, SD = 0.4, range 1–5). The caring subscale was the highest (3.9); the professionalism and the activism subscales had the same mean (3.3). Male students, studying in private universities and employed in health care, scored higher (p = .002, .001, and .01, respectively). Study track and age were insignificantly correlated.

CONCLUSION
The development of professional values is associated positively with practice and employment status; clinical experience improved students’ sense of professionalism.
Reversing Rivaroxaban Anticoagulation as Part of a Multimodal Hemostatic Intervention in a Polytrauma Animal Model
Authors: Rayatdoost Farahnaz , Braunschweig Till , Maron Benjamin , Schöchl Herbert , Akman Necib , Rossaint Rolf , Herzog Eva , Heitmeier Stefan , Grottke Oliver 
Published: August 2021

Background
Life-threatening bleeding requires prompt reversal of the anticoagulant effects of factor Xa inhibitors. This study investigated the effectiveness of four-factor prothrombin complex concentrate in treating trauma-related hemorrhage with rivaroxaban-anticoagulation in a pig polytrauma model. This study also tested the hypothesis that the combined use of a low dose of prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate could improve its subtherapeutic effects.

Methods
Trauma (blunt liver injury and bilateral femur fractures) was induced in 48 anesthetized male pigs after 30 min of rivaroxaban infusion (1 mg/kg). Animals in the first part of the study received prothrombin complex concentrate (12.5, 25, and 50 U/kg). In the second part, animals were treated with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid or plus tranexamic acid and fibrinogen concentrate. The primary endpoint was total blood loss postinjury. The secondary endpoints (panel of coagulation parameters and thrombin generation) were monitored for 240 min posttrauma or until death.

Results
The first part of the study showed that blood loss was significantly lower in the 25 U/kg prothrombin complex concentrate (1,541 ± 269 ml) and 50 U/kg prothrombin complex concentrate (1,464 ± 108 ml) compared with control (3,313 ± 634 ml), and 12.5 U/kg prothrombin complex concentrate (2,671 ± 334 ml, all P < 0.0001). In the second part of the study, blood loss was significantly less in the 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate (1,836 ± 556 ml, P < 0.001) compared with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid (2,910 ± 856 ml), and there were no early deaths in the 25 U/kg prothrombin complex concentrate, 50 U/kg prothrombin complex concentrate, and 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate groups. Histopathologic analyses postmortem showed no adverse events.

Conclusions
Prothrombin complex concentrate effectively reduced blood loss, restored hemostasis, and balanced thrombin generation. A multimodal hemostatic approach using tranexamic acid plus fibrinogen concentrate enhanced the effect of low doses of prothrombin complex concentrate, potentially reducing the prothrombin complex concentrate doses required for effective bleeding control.

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“Damage Control” Fixation of Displaced Femoral Neck Fractures in High-Risk Elderly Patients: A Feasibility Case Series
Authors: Konda Sanjit R. , Dedhia Nicket , Rettig Samantha , Davidovitch Roy , Ganta Abhishek , Egol Kenneth A. 
Published: August 2021

Objectives:
To assess the outcomes of patients who underwent closed reduction and percutaneous pinning (CRPP) with cannulated screws for treatment of a displaced femoral neck fracture (DFNF) as they were deemed too high risk to undergo hemiarthroplasty (HA).

Design:
Prospective cohort study.

Setting:
One urban academic medical center.

Patients/Participants:
Sixteen patients treated with CRPP and 32 risk-level–matched patients treated with HA.

Intervention:
CRPP for patients with DFNFs who were deemed too ill to undergo HA. The concept being that CRPP would aid in pain control and facilitate mobilization and if failed, the patient could return electively after medical optimization for conversion to arthroplasty.

Main Outcome Measurements:
Complications, readmissions, mortality, inpatient cost, and functional status.

Results:
The CRPP cohort had a greater incidence of exacerbations of chronic medical conditions or new onset of acute illness and an elevated mean American Society of Anesthesiologist score. There were no differences in discharge location, length of stay, major complication rate, ambulation before discharge, or 90-day readmission rate. Patients undergoing CRPP were less likely to experience minor complications including a significantly decreased incidence of acute blood loss anemia. Three patients (18.7%) in the CRPP cohort underwent conversion to HA or THA. There was no difference in inpatient, 30-day, or 1-year mortality.

Conclusion:
In the acutely ill patients with DFNFs, “damage control” fixation with CRPP can be safely performed in lieu of HA to stabilize the fracture in those unable to tolerate anesthesia or the sequelae of major surgery. Patients should be followed closely to evaluate the need for secondary surgery.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of Levels of Evidence.