bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor organoids to study gastroesophageal cancer: a primer
Authors: Jin Ramon U , Mills Jason C 
Published: July 2020

Abstract
Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. However, we currently cannot monitor successful gene/pathway targeting, nor understand how/when tumors develop resistance, nor predict which patients will derive maximal benefit. To improve outcomes, we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual patients. To this end, patient-derived organoids, in which tumor cells from individual patients are grown in a Petri dish, are a new versatile system that allows for timely expandability, detailed molecular characterization, and genetic manipulation with the promise of enabling predictive assessment of treatment response. In this review, we will explore the development and basic techniques for organoid generation, and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.
Unexpected arteriovenous malformation of the thyroid resulting in significant intraoperative blood loss
Authors: Ajadi Ebunoluwa , Dueber Julie , Randle Reese W , Lee Cortney Y 
Published: July 2020

Abstract
A 49-year-old morbidly obese woman with metastatic endometrial carcinoma was referred for evaluation of an incidentally identified large right thyroid nodule found on computed tomography performed for cancer evaluation. Ultrasound revealed a 9.7 cm solid isoechoic homogeneous right thyroid nodule. Fine needle aspiration was benign. Given size, resection was recommended following completion of chemotherapy and radiation. At the time of right thyroid lobectomy, extremely large vessels were encountered, and the procedure was complicated by estimated blood loss of 2 L. Final pathology revealed a large, benign adenomatous nodule and vascular features consistent with arteriovenous malformation (AVM). Unlike previously reported cases, the diagnosis of a thyroid AVM was not known preoperatively.
Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility
Authors: Wilkes Sean , Ona Celia , Yang Michael , Liu Pingyang , Benton Amber , Lustik Michael , Coleman John 
Published: July 2020

Abstract

Introduction
Repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression has been studied for over two decades. Repetitive TMS was approved by the Food and Drug Administration in 2008 for the treatment of depression after at least one failed trial of an antidepressant medication of adequate dose and duration. This study evaluated whether rTMS treatments may be associated with measurable improvements in depression and post-traumatic stress disorder (PTSD) symptoms for treated military beneficiaries in Hawaii suffering from depression. It also examined the number of failed medication trials that patients underwent before rTMS treatment.

Materials and Methods
A retrospective chart review of 77 rTMS patients who received and completed treatment between January 1, 2010 and October 31, 2016 was performed. Under a typical treatment regimen, patients receive rTMS for 6 weeks as well as weekly psychiatric assessments, which included completion of Beck’s Depression Inventory (BDI) and PTSD Checklist (PCL). A mixed model repeated measures analysis was done assuming an autoregressive order one covariance structure to evaluate changes over time. Adjusted analyses were done to assess whether changes over time differed by age, prior diagnosis of PTSD, active duty status, and gender.

Results
The majority of patients were from the army (74%) and 56% were on active duty. Just over half (53%) were male. Most patients (52%) had completed trials of three or more different antidepressant medications before initiation of treatment with rTMS. The mean number of antidepressant trials was 2.7. BDI and PCL scores were significantly lower at end of treatment on average compared to the pretreatment baseline scores. Mean differences for BDI and PCL were significant with P &lt; 0.001 15, 30, and 45 days after TMS treatment was initiated. Overall, 44% of patients experienced a reduction ≥10 points on BDI, and 38% experienced a reduction ≥10 points on PCL. Additionally, scores fell similarly regardless of whether or not patients had a comorbid diagnosis of PTSD.

Conclusions
Our research suggests that rTMS treatments may produce a reduction in symptoms of both depression and PTSD in patients with refractory depression and comorbid PTSD. It may be a useful alternative to antidepressants in the treatment of depression in the military population, including those with comorbid PTSD. Broader implementation of this treatment modality may prove beneficial for the purposes of military readiness, given current policies and restrictions on service members who are initiated on antidepressant medications.
Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma
Authors: Armstrong Chris W D , Coulter Jonathan A , Ong Chee Wee , Maxwell Pamela J , Walker Steven , Butterworth Karl T , Lyubomska Oksana , Berlingeri Silvia , Gallagher Rebecca , O’Sullivan Joe M , Jain Suneil , Mills Ian G , Prise Kevin M , Bristow Robert G , LaBonte Melissa J , Waugh David J J 
Published: July 2020

Abstract
Functional impairment of the tumour suppressor PTEN is common in primary prostate cancer and has been linked to relapse post-radiotherapy (post-RT). Pre-clinical modelling supports elevated CXC chemokine signalling as a critical mediator of PTEN-depleted disease progression and therapeutic resistance. We assessed the correlation of PTEN deficiency with CXC chemokine signalling and its association with clinical outcomes. Gene expression analysis characterized a PTENLOW/CXCR1HIGH/CXCR2HIGH cluster of tumours that associates with earlier time to biochemical recurrence [hazard ratio (HR) 5.87 and 2.65, respectively] and development of systemic metastasis (HR 3.51). In vitro, CXCL signalling was further amplified following exposure of PTEN-deficient prostate cancer cell lines to ionizing radiation (IR). Inhibition of CXCR1/2 signalling in PTEN-depleted cell-based models increased IR sensitivity. In vivo, administration of a CXCR1/2-targeted pepducin (x1/2pal-i3), or CXCR2-specific antagonist (AZD5069), in combination with IR to PTEN-deficient xenografts attenuated tumour growth and progression compared to control or IR alone. Post-mortem analysis confirmed that x1/2pal-i3 administration attenuated IR-induced CXCL signalling and anti-apoptotic protein expression. Interventions targeting CXC chemokine signalling may provide an effective strategy to combine with RT in locally advanced prostate cancer patients with known presence of PTEN-deficient foci.
MinYS: mine your symbiont by targeted genome assembly in symbiotic communities
Authors: Guyomar Cervin , Delage Wesley , Legeai Fabrice , Mougel Christophe , Simon Jean-Christophe , Lemaitre Claire 
Published: July 2020

Abstract
Most metazoans are associated with symbionts. Characterizing the effect of a particular symbiont often requires getting access to its genome, which is usually done by sequencing the whole community. We present MinYS, a targeted assembly approach to assemble a particular genome of interest from such metagenomic data. First, taking advantage of a reference genome, a subset of the reads is assembled into a set of backbone contigs. Then, this draft assembly is completed using the whole metagenomic readset in a de novo manner. The resulting assembly is output as a genome graph, enabling different strains with potential structural variants coexisting in the sample to be distinguished. MinYS was applied to 50 pea aphid resequencing samples, with variable diversity in symbiont communities, in order to recover the genome sequence of its obligatory bacterial symbiont, Buchnera aphidicola. It was able to return high-quality assemblies (one contig assembly in 90% of the samples), even when using increasingly distant reference genomes, and to retrieve large structural variations in the samples. Because of its targeted essence, it outperformed standard metagenomic assemblers in terms of both time and assembly quality.
Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study
Authors: Wu Hemmings , Adler Sarah , Azagury Dan E , Bohon Cara , Safer Debra L , Barbosa Daniel A N , Bhati Mahendra T , Williams Nolan R , Dunn Laura B , Tass Peter A , Knutson Brian D , Yutsis Maya , Fraser Ayesha , Cunningham Tricia , Richardson Kara , Skarpaas Tara L , Tcheng Thomas K , Morrell Martha J , Roberts Laura Weiss , Malenka Robert C , Lock James D , Halpern Casey H 
Published: July 2020

Abstract

BACKGROUND
Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study.

OBJECTIVE
To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity.

METHODS
This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed.

EXPECTED OUTCOMES
Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation.

DISCUSSION
This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.
Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration
Authors: Rezk Rasha , Jia Bill Zong , Wendler Astrid , Dimov Ivan , Watts Colin , Markaki Athina E , Franze Kristian , Kabla Alexandre J 
Published: July 2020

AbstractBackgroundGlioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although the motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited. This study aims to investigate the adhesion properties within and between patients’ tumors on a cellular level and test whether these properties correlate with cell migration.MethodsSix tissue samples were taken from spatially separated sections during 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. Navigated biopsy samples were collected from strongly fluorescent tumor cores, a weak fluorescent tumor rim, and nonfluorescent tumor margins. A microfluidics device was built to induce controlled shear forces to detach cells from monolayer cultures. Cells were cultured on low modulus polydimethylsiloxane representative of the stiffness of brain tissue. Cell migration and morphology were then obtained using time-lapse microscopy.ResultsGBM cell populations from different tumor fractions of the same patient exhibited different migratory and adhesive behaviors. These differences were associated with sampling location and amount of 5-ALA fluorescence. Cells derived from weak- and nonfluorescent tumor tissue were smaller, adhered less well, and migrated quicker than cells derived from strongly fluorescent tumor mass.ConclusionsGBM tumors are biomechanically heterogeneous. Selecting multiple populations and broad location sampling are therefore important to consider for drug testing.
Drugs for Gram-Negative Bugs From 2010–2019: A Decade in Review
Authors: Pontefract Benjamin A , Ho Hong T , Crain Alexandria , Kharel Madan K , Nybo S Eric 
Published: July 2020

AbstractA literature review spanning January 1, 2010, to December 31, 2019, was conducted using the PubMed and ISI Web of Science databases to determine the breadth of publication activity in the area of gram-negative bacteria antimicrobial therapy. The number of articles was used as a reflection of scholarly activity. First, PubMed was searched using the following Medical Subject Headings (MeSH): antibacterial agents, Enterobacteriaceae, Acinetobacter, and Pseudomonas. A total of 12 643 articles were identified within PubMed, and 77 862 articles were identified within ISI Web of Science that included these terms. Second, these articles were categorized by antibiotic class to identify relative contributions to the literature by drug category. Third, these studies were used to identify key trends in the treatment of gram-negative bacterial infections from the past decade. This review highlights advances made in the past 10 years in antibacterial pharmacotherapy and some of the challenges that await the next decade of practice.
Weak-lensing clusters from HSC survey first-year data: Mitigating the dilution effect of foreground and cluster-member galaxies
Authors: Hamana Takashi , Shirasaki Masato , Lin Yen-Ting 
Published: July 2020

Abstract
We present a weak-lensing cluster search using Hyper Suprime-Cam Subaru Strategic Program (HSC survey) first-year data. We pay special attention to the dilution effect of cluster-member and foreground galaxies on weak-lensing signals from clusters of galaxies; we adopt the globally normalized weak-lensing estimator which is least affected by cluster-member galaxies, and we select source galaxies by using photometric redshift information to mitigate the effect of foreground galaxies. We produce six samples of source galaxies with different low-z galaxy cuts, construct weak-lensing mass maps for each source sample, and search for high peaks in the mass maps that cover an effective survey area of ∼120 deg2. We combine six catalogs of high peaks into a sample of cluster candidates which contains 124 high peaks with signal-to-noise ratios greater than five. We cross-match the peak sample with the public optical cluster catalog constructed from the same HSC survey data to identify cluster counterparts of the peaks. We find that 107 out of 124 peaks have matched clusters within 5′ of peak positions. Among them, we define a subsample of 64 secure clusters that we use to examine dilution effects on our weak-lensing cluster search. We find that source samples with low-z galaxy cuts mitigate the dilution effect on weak-lensing signals of high-z clusters ($z \gtrsim 0.3$), and thus combining multiple peak catalogs from different source samples improves the efficiency of weak-lensing cluster searches.
Neurometabolic Correlates of Reactive and Proactive Motor Inhibition in Young and Older Adults: Evidence from Multiple Regional 1H-MR Spectroscopy
Authors: Weerasekera Akila , Levin Oron , Clauwaert Amanda , Heise Kirstin-Friederike , Hermans Lize , Peeters Ronald , Mantini Dante , Cuypers Koen , Leunissen Inge , Himmelreich Uwe , Swinnen Stephan P 
Published: July 2020

Abstract
Suboptimal inhibitory control is a major factor contributing to motor/cognitive deficits in older age and pathology. Here, we provide novel insights into the neurochemical biomarkers of inhibitory control in healthy young and older adults and highlight putative neurometabolic correlates of deficient inhibitory functions in normal aging. Age-related alterations in levels of glutamate–glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mIns) were assessed in the right inferior frontal gyrus (RIFG), pre-supplementary motor area (preSMA), bilateral sensorimotor cortex (SM1), bilateral striatum (STR), and occipital cortex (OCC) with proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 30 young (age range 18–34 years) and 29 older (age range 60–74 years) adults. Associations between age-related changes in the levels of these metabolites and performance measures or reactive/proactive inhibition were examined for each age group. Glx levels in the right striatum and preSMA were associated with more efficient proactive inhibition in young adults but were not predictive for reactive inhibition performance. Higher NAA/mIns ratios in the preSMA and RIFG and lower mIns levels in the OCC were associated with better deployment of proactive and reactive inhibition in older adults. Overall, these findings suggest that altered regional concentrations of NAA and mIns constitute potential biomarkers of suboptimal inhibitory control in aging.
Bio-evaluation of the role of chitosan and curcumin nanoparticles in ameliorating genotoxicity and inflammatory responses in rats’ gastric tissue followed hydroxyapatite nanoparticles’ oral uptake
Authors: Mosa Israa F , Abd Haitham H , Abuzreda Abdelsalam , Assaf Nadhom , Yousif Amenh B 
Published: July 2020

AbstractHydroxyapatite has been extensively used in tissue engineering due to its osteogenic potency, but its present toxicological facts are relatively insufficient. Here, the possible gastric toxicity of hydroxyapatite nanoparticles was evaluated biochemically to determine oxidant and antioxidant parameters in rats’ stomach tissues. At results, hydroxyapatite nanoparticles have declined stomach antioxidant enzymes and reduced glutathione level, while an induction in lipid peroxidation and nitric oxide has been observed. Furthermore, DNA oxidation was analyzed by the suppression of toll-like receptors 2, nuclear factor-kappa B and Forkhead box P3 gene expression and also 8-Oxo-2′-deoxyguanosine level as a genotoxicity indicator. Various pro-inflammatory gene products have been identified that intercede a vital role in proliferation and apoptosis suppression, among these products: tumor suppressor p53, tumor necrosis factor-α and interliukin-6. Moreover, the hydroxyapatite-treated group revealed wide histological alterations and significant elevation in the number of proliferating cell nuclear antigen-positive cells, which has been observed in the mucosal layer of the small intestine, and these alterations are an indication of small intestine injury, while the appearance of chitosan and curcumin nanoparticles in the combination group showed improvement in all the above parameters with inhibition of toxic-oxidant parameters and activation of antioxidant parameters.
Intraoperative Fire Risk: Evaluating the 3-Minute Wait After Chlorhexidine-Alcohol Antiseptic Scrub
Authors: Ryan Sean P. , Adams Samuel B. , Allen Nicholas , Lazarides Alexander L. , Wellman Samuel S. , Gage Mark J. 
Published: July 2020

Objective:
We sought to determine the flammability of the skin at different time intervals after chlorhexidine-alcohol antiseptic scrub application, to provide evidence for hospital protocols recommending a 3-minute drying time.

Methods:
Swine feet, which contain the skin, subcutaneous tissue, muscle, and bone, were used for an experimental cohort. The skin was prepped with chlorhexidine-alcohol solution. Attempted ignition with an open flame was then performed in the presence of visible pooling, as well as at time points 0, 30, 60, and 90 seconds after application, in addition to when the skin appeared visibly dry. Six samples were used for each time point tested.

Results:
At time 0 seconds and with gross pooling, ignition was achieved with all samples tested. However, at 30 seconds, only 2 of 6 samples were ignited (which appeared wet). No samples after 60 or 90 seconds were flammable. Samples appeared dry after an average of 40.5 seconds and were not able to ignite.

Conclusions:
Although our findings do support that a chlorhexidine-alcohol antiseptic scrub is a potentially flammable surgical prep solution, we found little support for a 3-minute time cutoff. More importantly, the presence of pooling and persistently wet appearing prep is a more important fire risk than the time elapsed after prep application. Caution should be used when working with any flammable solution, and efforts to minimize chemical burns and combustion should be sought based on evidence.
Radiotherapy for Adult Soft Tissue Sarcomas of the Head and Neck
Authors: O’steen Lillie , Saldivar Brittany , Kharod Shivam , Bassett Benjamin , Morris Christopher G. , Mendenhall William M. 
Published: July 2020

Objective:
Surgery followed by postoperative radiation therapy (RT) is the standard of care for soft tissue sarcomas (STS) of the head and neck that are high grade or have close or positive margins.

Methods:
The authors retrospectively reviewed adult patients with head and neck STS treated with RT at a single institution between 1981 and 2017. All patients who were 19 years and older with STS of the head and neck—excluding rhabdomyosarcoma, angiosarcoma, and Ewing tumors—were included in this study. Toxicity was graded using Common Terminology Criteria for Adverse Events (CTCAE), version 4.

Results:
Among 34 patients with head and neck STS treated with postoperative RT (33) or primary RT (1) who met the inclusion criteria, the median age at diagnosis was 45 years (range, 20 to 83). Overall, 37% had T1 tumors, 50% had high-grade histology (grade 3), and 26% had microscopically positive margins. The median RT dose was 65 Gy to the primary site; 29% received elective nodal irradiation. The median follow-up for living patients was 16.6 years (range, 0.6 to 30). At 5 and 10 years, the local control rates were 88% and 80%, the regional control rates were 97% and 97%, the freedom from distant metastases rates were 100% and 100%, the cause-specific survival rates were 88% and 81%, and the overall survival rates were 85% and 69%. Two patients (6%) developed late grade 3+ complications.

Conclusion:
Our study demonstrates that surgery and radiotherapy for STS of the head and neck have excellent disease outcomes.