bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma
Authors: Ailawadhi Sikander , Sexton Rachael , Lentzsch Suzanne , Abidi Muneer H. , Voorhees Peter M. , Cohen Adam D. , Rohren Eric M. , Heitner Stephen , Kelly Kevin , Mackler Niklas J. , Baer David M. , Hoering Antje , Durie Brian , Orlowski Robert Z. 
Published: April 2020

Abstract

Purpose:
Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits.

Patients and Methods:
We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment.

Results:
Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821–1.370; P = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841–.571; P = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs.

Conclusions:
This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
A Multianalyte Panel Consisting of Extracellular Vesicle miRNAs and mRNAs, cfDNA, and CA19-9 Shows Utility for Diagnosis and Staging of Pancreatic Ductal Adenocarcinoma
Authors: Yang Zijian , LaRiviere Michael J. , Ko Jina , Till Jacob E. , Christensen Theresa , Yee Stephanie S. , Black Taylor A. , Tien Kyle , Lin Andrew , Shen Hanfei , Bhagwat Neha , Herman Daniel , Adallah Andrew , O'Hara Mark H. , Vollmer Charles M. , Katona Bryson W. , Stanger Ben Z. , Issadore David , Carpenter Erica L. 
Published: April 2020

Abstract

Purpose:
To determine whether a multianalyte liquid biopsy can improve the detection and staging of pancreatic ductal adenocarcinoma (PDAC).

Experimental Design:
We analyzed plasma from 204 subjects (71 healthy, 44 non-PDAC pancreatic disease, and 89 PDAC) for the following biomarkers: tumor-associated extracellular vesicle miRNA and mRNA isolated on a nanomagnetic platform that we developed and measured by next-generation sequencing or qPCR, circulating cell-free DNA (ccfDNA) concentration measured by qPCR, ccfDNA KRAS G12D/V/R mutations detected by droplet digital PCR, and CA19-9 measured by electrochemiluminescence immunoassay. We applied machine learning to training sets and subsequently evaluated model performance in independent, user-blinded test sets.

Results:
To identify patients with PDAC versus those without, we generated a classification model using a training set of 47 subjects (20 PDAC and 27 noncancer). When applied to a blinded test set (N = 136), the model achieved an AUC of 0.95 and accuracy of 92%, superior to the best individual biomarker, CA19-9 (89%). We next used a cohort of 20 patients with PDAC to train our model for disease staging and applied it to a blinded test set of 25 patients clinically staged by imaging as metastasis-free, including 9 subsequently determined to have had occult metastasis. Our workflow achieved significantly higher accuracy for disease staging (84%) than imaging alone (accuracy = 64%; P &lt; 0.05).

Conclusions:
Algorithmically combining blood-based biomarkers may improve PDAC diagnostic accuracy and preoperative identification of nonmetastatic patients best suited for surgery, although larger validation studies are necessary.
Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity
Authors: Bruun Jarle , Kryeziu Kushtrim , Eide Peter W. , Moosavi Seyed H. , Eilertsen Ina A. , Langerud Jonas , Røsok Bård , Totland Max Z. , Brunsell Tuva H. , Pellinen Teijo , Saarela Jani , Bergsland Christian H. , Palmer Hector G. , Brudvik Kristoffer W. , Guren Tormod , Dienstmann Rodrigo , Guren Marianne G. , Nesbakken Arild , Bjørnbeth Bjørn Atle , Sveen Anita , Lothe Ragnhild A. 
Published: April 2020

AbstractPurpose:Molecular tumor heterogeneity may have important implications for the efficacy of targeted therapies in metastatic cancers. Inter-metastatic heterogeneity of sensitivity to anticancer agents has not been well explored in colorectal cancer.Experimental Design:We established a platform for ex vivo pharmacogenomic profiling of patient-derived organoids (PDO) from resected colorectal cancer liver metastases. Drug sensitivity testing (n = 40 clinically relevant agents) and gene expression profiling were performed on 39 metastases from 22 patients.Results:Three drug–response clusters were identified among the colorectal cancer metastases, based primarily on sensitivities to EGFR and/or MDM2 inhibition, and corresponding with RAS mutations and TP53 activity. Potentially effective therapies, including off-label use of drugs approved for other cancer types, could be nominated for eighteen patients (82%). Antimetabolites and targeted agents lacking a decisive genomic marker had stronger differential activity than most approved chemotherapies. We found limited intra-patient drug sensitivity heterogeneity between PDOs from multiple (2–5) liver metastases from each of ten patients. This was recapitulated at the gene expression level, with a highly proportional degree of transcriptomic and pharmacological variation. One PDO with a multi-drug resistance profile, including resistance to EGFR inhibition in a RAS-mutant background, showed sensitivity to MEK plus mTOR/AKT inhibition, corresponding with low-level PTEN expression.Conclusions:Intra-patient inter-metastatic pharmacological heterogeneity was not pronounced and ex vivo drug screening may identify novel treatment options for metastatic colorectal cancer. Variation in drug sensitivities was reflected at the transcriptomic level, suggesting potential to develop gene expression–based predictive signatures to guide experimental therapies.
A20 and RBX1 Regulate Brentuximab Vedotin Sensitivity in Hodgkin Lymphoma Models
Authors: Wei Wei , Lin Yuquan , Song Zhihui , Xiao Wenming , Chen Liqi , Yin Jiejing , Zhou Yan , Barta Stefan K. , Petrus Michael , Waldmann Thomas A. , Yang Yibin 
Published: April 2020

Abstract

Purpose:
For patients with refractory/relapsed Hodgkin lymphoma (roughly 20% of total cases), few effective therapeutic options exist. Currently, brentuximab vedotin (BV), a drug-conjugated anti-CD30 antibody, is one of the most effective approved therapy agents for these patients. However, many patients do not achieve complete remission and ultimately develop BV-resistant disease, necessitating a more detailed understanding of the molecular circuitry that drives BV sensitivity and the mechanism of BV resistance.

Experimental Design:
Here, we established a ubiquitin regulator–focused CRISPR library screening platform in Hodgkin lymphoma and carried out a drug sensitization screen against BV to identify genes regulating BV treatment sensitivity.

Results:
Our CRISPR library screens revealed the ubiquitin-editing enzymes A20 and RBX1 as key molecule effectors that regulate BV sensitivity in Hodgkin lymphoma line L428. A20 negatively regulates NF-κB activity which is required to prevent BV cytotoxicity. In line with these results, the RNA-seq analysis of the BV-resistant single-cell clones demonstrated a consistent upregulation of NF-κB signature genes, as well as the ABC transporter gene ABCB1. Mechanically, NF-κB regulates BV treatment sensitivity through mediating ABCB1 expression. Targeting NF-κB activity synergized well with BV in killing Hodgkin lymphoma cell lines, augmented BV sensitivity, and overcame BV resistance in vitro and in Hodgkin lymphoma xenograft mouse models.

Conclusions:
Our identification of this previously unrecognized mechanism provides novel knowledge of possible BV responsiveness and resistance mechanisms in Hodgkin lymphoma, as well as leads to promising hypotheses for the development of therapeutic strategies to overcome BV resistance in this disease.
Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention
Authors: Shah Binita , Pillinger Michael , Zhong Hua , Cronstein Bruce , Xia Yuhe , Lorin Jeffrey D. , Smilowitz Nathaniel R. , Feit Frederick , Ratnapala Nicole , Keller Norma M. , Katz Stuart D. 
Published: April 2020

Background:
Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown.

Methods:
In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo.

Results:

Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%,
P
=0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%,
P
=0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%,
P
=0.49) did not differ between colchicine and placebo groups. Among 280 PCI subjects in a nested inflammatory biomarker substudy, the primary biomarker end point, change in interleukin-6 concentrations did not differ between groups 1-hour post-PCI but increased less 24 hours post-PCI in the colchicine (n=141) versus placebo group (n=139; 76% [−6 to 898] versus 338% [27 to 1264],
P
=0.02). High-sensitivity C-reactive protein concentration also increased less after 24 hours in the colchicine versus placebo groups (11% [−14 to 80] versus 66% [1 to 172],
P
=0.001).

Conclusions:
Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique Identifiers: NCT02594111, NCT01709981.
Misdiagnosis of Cervicocephalic Artery Dissection in the Emergency Department
Authors: Liberman Ava L. , Navi Babak B. , Esenwa Charles C. , Zhang Cenai , Song Justin , Cheng Natalie T. , Labovitz Daniel L. , Kamel Hooman , Merkler Alexander E. 
Published: April 2020

Background and Purpose—
Cervicocephalic artery dissection is an important cause of stroke. The clinical presentation of dissection can resemble that of benign neurological conditions leading to delayed or missed diagnosis.

Methods—

We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. Using validated
International Classification of Diseases, Ninth Revision, CM codes
, we identified adult patients hospitalized for cervicocephalic artery dissection. We defined probable misdiagnosis of dissection as having an Emergency Department treat-and-release visit for symptoms or signs of dissection, including headache, neck pain, and focal neurological deficits in the 14 days before dissection diagnosis. Multivariable logistic regression was used to compare adverse clinical outcomes in patients with and without probable misdiagnosis.

Results—
Among 7090 patients diagnosed with a dissection (mean age 52.7 years, 44.9% women), 218 (3.1% [95% CI, 2.7%–3.5%]) had a preceding probable Emergency Department misdiagnosis. After adjustment for demographics and vascular risk factors, there were no differences in rates of stroke (odds ratio, 0.82 [95% CI, 0.62–1.09]) or in-hospital death (odds ratio, 0.26 [95% CI, 0.07–1.08]) between dissection patients with and without a probable misdiagnosis at index hospitalization.

Conclusions—
We found that ≈1 in 30 dissection patients was probably misdiagnosed in the 2 weeks before their diagnosis.
Thirst as an ingestive behavior: A brief review on physiology and assessment
Authors: Adams JD , Myatich Ali I , McCullough Alexis S 
Published: April 2020

Background: Thirst is a sensation normally aroused by a lack of water and associated with a desire to drink more fluid. Aim: The aims of this brief review are twofold: (a) to summarize the thirst mechanism in how it is initiated and diminished, and (b) to describe techniques to assess human thirst accurately in a variety of situations. Discussion: Thirst is maintained via a feedback-controlled mechanism, regulated by central and peripheral factors, as well as social and psychological cues. Most studies of thirst have focused on the initiation of water intake and the neural mechanisms responsible for this vital behavior. Less attention has been paid to the stimuli and mechanisms that terminate a bout of drinking and limit fluid ingestion, such as oropharyngeal and gastric signals, coupled with osmotic sensations. Thirst perception is typically assessed by subjective ratings using a variety of questionnaires, rankings, or visual analog scales. However, the appropriate perceptual tool may not always be used for the correct assessment of thirst perception. Conclusions: In considering the many factors involved in thirst arousal and inhibition, similar questions need to be considered for the correct assessment of this ingestive behavior.
Outcome of Biomedical Waste Management Training Among Staff Nurses of Primary Health Centers of Hassan District
Authors: Gonibeedu Venkatesh , Sundar M. , Santhosh H. C. , Mallikarjuna Swamy D. 
Published: April 2020

Introduction Inadequate biomedical waste management not only poses significant risk of infection due to pathogens such as HIV and Hepatitis B and C virus but also carries the risk of water, air, and soil pollution thereby adversely affecting the environment and community at large. Therefore, the Ministry of Health and Family Welfare commissioned implementation of an Infection Management and Environment Plan (IMEP) in health-care facilities. Hence, this study is undertaken to assess the knowledge, attitude, practice, and gaps in implementing the biomedical waste management practices at the primary health-care facilities. Methodology: A cross-sectional study was conducted among the Primary Health Centers of Hassan District. Details of knowledge, attitude, and practice of biomedical waste management were collected through observation, staff interview, and record review on the predesigned questionnaire. A score of 0, 1, and 2 was given for noncompliant (0), partially compliant (1), and fully compliant (2), respectively, based on the compliance. A scoring system was devised to evaluate the effectiveness of training as good, average, and poor. A score of >70 was considered as good, 50 to 70 as average, and <50 as poor. Results The mean efficacy score was 63; knowledge was good with a score of 74, attitude was average with a score of 63, and practice was also average with a score of 54. Conclusion There is a need for retraining of all the staff and strict supportive supervision by the district health authorities to ease the implementation requirements.
Dual-energy CT to differentiate gallbladder polyps: cholesterol versus adenomatous
Authors: Yin Sheng Nan , Chi Jing , Liu Li , Ding Ning , Ji Yi Ding , Yuan Jian Mao 
Published: April 2020

Background Dual-energy computed tomography (DE-CT) scans were acquired to identify cholesterol and adenomatous gallbladder (GB) polyps, which have not been well evaluated before surgery. Purpose To evaluate the DE-CT findings of GB polyps 1.0–2.0 cm in size and differentiate between cholesterol and adenomatous polyps. Material and Methods Forty-six patients with GB polyps were surgically treated from December 2017 to December 2019 and divided into two groups according to their postoperative pathologic results: a cholesterol group with 26 patients and an adenomatous group with 20 patients. All of these patients underwent DE-CT imaging with tube voltages of 80 kVp and 140 kVp within two weeks before surgery. Mean attenuation values were measured for every GB polyp at 80/140 kVp and at 40/140 keV. The mean attenuation value changes between 140 kVp and 80 kVp (MAVC140–80 kVp) and mean attenuation value changes between 100 keV and 40 keV (MAVC100–40 keV) were calculated. Results The CT image parameters of all 46 patients with GB polyps were analyzed. There were significant differences in MAVC140–80 kVp and MAVC100–40 keV between cholesterol and adenomatous polyps ( P <0.05); these values were positive for cholesterol polyps and negative for adenomatous polyps. Conclusion The unique energy spectrum information provided by DE-CT scans is helpful in differentiating between cholesterol and adenomatous polyps 1.0–2.0 cm in size.
Arterial spin labeling magnetic resonance imaging at short post-labeling delay reflects cerebral perfusion pressure verified by oxygen-15-positron emission tomography in cerebrovascular steno-occlusive disease
Authors: Itagaki Hiroshi , Kokubo Yasuaki , Kawanami Kanako , Sato Shinji , Yamada Yuki , Sato Shinya , Sonoda Yukihiko 
Published: April 2020

Background Arterial transit time correction by data acquisition with multiple post-labeling delays (PLDs) or relatively long PLDs is expected to obtain more accurate imaging in cases of the cerebrovascular steno-occlusive disease. However, there have so far been no reports describing the significance of arterial spin labeling (ASL) images at short PLDs regarding the evaluation of cerebral circulation in ischemic cerebrovascular disease. Purpose To clarify the role of short-PLD ASL in cerebrovascular steno-occlusive disease. Material and Methods Fifty-three patients with cerebrovascular steno-occlusive disease were included in this study. All patients underwent ASL magnetic resonance imaging and 15O-PET within two days of each modality. To compare the ASL findings with each parameter of PET, the right-to-left (R/L) ratio, defined as the right middle cerebral artery (MCA) value/left MCA value, was calculated. Results There is a significant correlation between the ASL images at a short PLD and the ratio of cerebral blood flow and cerebral blood volume by 15O-PET, which may accurately reflect the cerebral perfusion pressure. A receiver operating characteristic curve analysis indicated that ASL images at PLD 1000 and 1500 ms were more accurate than at PLD 2000–3000 ms for the detection of a ≥10% change in the PET cerebral blood flow. Conclusion ASL images at shorter PLDs may be useful at least as a screening modality to detect the changes in the cerebral circulation in cerebrovascular steno-occlusive disease. We must evaluate ASL images at multiple PLDs while considering the arterial transit time of each case at present.
Negative emotions in community-dwelling adults with prediabetes and hypertension
Authors: Zhuang Qianling , Wu Lirong , Ting Wang , Jie Lin , Zou Jingying , Du Jiangang 
Published: April 2020

Objective The purpose of this study was to investigate negative emotions and factors related to the risk of mental disorders in individuals with prediabetes and hypertension. Methods A total of 504 community-dwelling adult men and women in Suzhou, China, were enrolled and questionnaires used to obtain sociodemographic data, anxiety and depression scores, and current status of common metabolic indicators, including blood glucose level and blood pressure. Results Anxiety and depression scores in participants with prediabetes and hypertension were significantly higher than those in participants with normal blood glucose levels and normal blood pressure. Correlation analysis revealed that age, sex, smoking, duration of disease, physical activity, blood pressure and fasting plasma glucose levels were key factors accelerating the progression to both anxiety and depression in all participants. Conclusions More attention should be paid to negative emotions in individuals with prediabetes and hypertension. These findings could help to inform health providers in developing interventions for this population.
Physical Exercise Interventions Targeting Cognitive Functioning and the Cognitive Domains in Nondementia Samples: A Systematic Review of Meta-Analyses
Authors: Turner David T. , Hu Mandy X. , Generaal Ellen , Bos Daniel , Ikram M. Kamran , Heshmatollah Alis , Fani Lana , Ikram M. Arfan , Penninx Brenda W. J. H. , Cuijpers Pim 
Published: April 2020

Objective: We investigated whether physical exercise interventions improve cognitive functioning in nondementia populations. Methods: We conducted a systematic review of meta-analyses including only randomized controlled trials (RCTs). Two reviewers completed a systematic search of PubMed, Embase, PsychInfo, and Cochrane Controlled Register of Trials. Study characteristics, effect size data, and heterogeneity estimates were extracted and presented in tabular form. Methodological quality was assessed by 2 reviewers using the AMSTAR-2 checklist. The validity of results was considered based on AMSTAR-2 scores and study characteristics. Results: We included 11 meta-analyses: 6 focused on disease-free older adults and 5 on mild cognitive impairment (MCI) excluding dementia. These meta-analyses summarized 97 unique RCTs. Methodological quality ranged from critically low to high. For overall cognitive functioning, which was the outcome of 6 meta-analyses, 1 showed improvement due to exercise interventions in disease-free older adults ( g = 0.29, P < .01), while 2 reported nonsignificant effects. In patients with MCI, 3 meta-analyses reported significant benefits of exercise interventions on overall cognitive functioning ( g = 0.25-0.57, P < .01). For cognitive domains such as attention and memory, there was limited evidence of beneficial effects of exercise demonstrated in either disease-free or MCI samples. Conclusions: Exercise may improve overall cognitive functioning in disease-free older adults, but there is too little high-quality evidence to conclude whether this is achieved through improvement in any of the specific cognitive domains assessed. There is clearer evidence that exercise may improve cognitive functioning in MCI, but again there is limited evidence across most cognitive domains.