bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma
Authors: Jasielec Jagoda K. , Kubicki Tadeusz , Raje Noopur , Vij Ravi , Reece Donna , Berdeja Jesus , Derman Benjamin A. , Rosenbaum Cara A. , Richardson Paul , Gurbuxani Sandeep , Major Sarah , Wolfe Brittany , Stefka Andrew T. , Stephens Leonor , Tinari Kathryn M. , Hycner Tyler , Rojek Alexandra E. , Dytfeld Dominik , Griffith Kent A. , Zimmerman Todd M. , Jakubowiak Andrzej J. 
Published: July 2020

Abstract
In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point was met, with an sCR rate of 60% after 8 cycles. Depth of response improved over time. On intent-to-treat (ITT), the sCR rate reached 76%. The rate of minimal residual disease (MRD) negativity using modified ITT was 70% according to next-generation sequencing (&lt;10−5 sensitivity). After median follow-up of 56 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 72% and 84% for ITT, 85% and 91% for MRD-negative patients, and 57% and 72% for patients with high-risk cytogenetics. For high-risk patients who were MRD negative, 5-year rates were 77% and 81%. Grade 3 to 4 adverse events included neutropenia (34%), lymphopenia (32%), infection (22%), and cardiac events (3%). There was no grade 3 to 4 peripheral neuropathy. Patients with NDMM treated with KRd with ASCT achieved high rates of sCR and MRD-negative disease at the end of KRd consolidation. Extended KRd maintenance after consolidation contributed to deepening of responses and likely to prolonged PFS and OS. Safety and tolerability were manageable. This trial was registered at www.clinicaltrials.gov as #NCT01816971.
FK506 induces lung lymphatic endothelial cell senescence and downregulates LYVE-1 expression, with associated decreased hyaluronan uptake
Authors: Shrestha Shikshya , Cho Woohyun , Stump Benjamin , Imani Jewel , Lamattina Anthony M. , Louis Pierce H. , Pazzanese James , Rosas Ivan O. , Visner Gary , Perrella Mark A. , El-Chemaly Souheil 
Published: July 2020

Abstract
Background
Therapeutic lymphangiogenesis in an orthotopic lung transplant model has been shown to improve acute allograft rejection that is mediated at least in part through hyaluronan drainage. Lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expressed on the surface of lymphatic endothelial cells plays important roles in hyaluronan uptake. The impact of current immunosuppressive therapies on lung lymphatic endothelial cells is largely unknown. We tested the hypothesis that FK506, the most commonly used immunosuppressant after lung transplantation, induces lung lymphatic endothelial cell dysfunction.

Methods
Lung lymphatic endothelial cells were cultured in vitro and treated with FK506. Telomerase activity was measured using the TRAP assay. Protein expression of LYVE-1 and senescence markers p21 and β-galactosidase was assessed with western blotting. Matrigel tubulation assay were used to investigate the effects of FK506 on TNF-α-induced lymphangiogenesis. Dual luciferase reporter assay was used to confirm NFAT-dependent transcriptional regulation of LYVE-1. Flow cytometry was used to examine the effects of FK506 on LYVE-1 in precision-cut-lung-slices ex vivo and on hyaluronan uptake in vitro.

Results
In vitro, FK506 downregulated telomerase reverse transcriptase expression, resulting in decreased telomerase activity and subsequent induction of p21 expression and cell senescence. Treatment with FK506 decreased LYVE-1 mRNA and protein levels and resulted in decreased LEC HA uptake. Similar result showing reduction of LYVE-1 expression when treated with FK506 was observed ex vivo. We identified a putative NFAT binding site on the LYVE-1 promoter and cloned this region of the promoter in a luciferase-based reporter construct. We showed that this NFAT binding site regulates LYVE-1 transcription, and mutation of this binding site blunted FK506-dependent downregulation of LYVE-1 promoter-dependent transcription. Finally, FK506-treated lymphatic endothelial cells show a blunted response to TNF-α-mediated lymphangiogenesis.

Conclusion
FK506 alters lymphatic endothelial cell molecular characteristics and causes lymphatic endothelial cell dysfunction in vitro and ex vivo. These effects of FK506 on lymphatic endothelial cell may impair the ability of the transplanted lung to drain hyaluronan macromolecules in vivo. The implications of our findings on the long-term health of lung allografts merit more investigation.
Genome-wide scan for common variants associated with intramuscular fat and moisture content in rainbow trout
Authors: Ali Ali , Al-Tobasei Rafet , Lourenco Daniela , Leeds Tim , Kenney Brett , Salem Mohamed 
Published: July 2020

Abstract
Background
Genetic improvement of fillet quality attributes is a priority of the aquaculture industry. Muscle composition impacts quality attributes such as flavor, appearance, texture, and juiciness. Fat and moisture make up about ~ 80% of the tissue weight. The genetic architecture underlying the fat and moisture content of the muscle is still to be fully explored in fish. A 50 K gene transcribed SNP chip was used for genotyping 789 fish with available phenotypic data for fat and moisture content. Genotyped fish were obtained from two consecutive generations produced in the National Center for Cool and Cold Water Aquaculture (NCCCWA) growth-selective breeding program. Estimates of SNP effects from weighted single-step GBLUP (WssGBLUP) were used to perform genome-wide association (GWA) analysis to identify quantitative trait loci (QTL) associated with the studied traits.

Results
Using genomic sliding windows of 50 adjacent SNPs, 137 and 178 SNPs were identified as associated with fat and moisture content, respectively. Chromosomes 19 and 29 harbored the highest number of SNPs explaining at least 2% of the genetic variation in fat and moisture content. A total of 61 common SNPs on chromosomes 19 and 29 affected the aforementioned traits; this association suggests common mechanisms underlying intramuscular fat and moisture content. Additionally, based on single-marker GWA analyses, 8 and 24 SNPs were identified in association with fat and moisture content, respectively.

Conclusion
SNP-harboring genes were primarily involved in lipid metabolism, cytoskeleton remodeling, and protein turnover. This work provides putative SNP markers that could be prioritized and used for genomic selection in breeding programs.
Clinical performance of the LMA Protector™ airway in moderately obese patients
Authors: Shariffuddin Ina Ismiarti , Chaw Sook Hui , Ng Ling Wei , Lim Ching Hooi , Zainal Abidin Mohd Fitry , Wan Zakaria Wan A. , Teoh Wendy H. 
Published: July 2020

Abstract
Background
The 4th National Audit Project of The Royal College of Anaesthetists and The Difficult Airway Society (NAP4) reported a higher incidence of supraglottic airway device (SAD) related pulmonary aspiration in obese patients especially with the first-generation SADs. The latest single-use SAD, the Protector™ provides a functional separation of the respiratory and digestive tracts and its laryngeal cuff with two ports allowing additional suction in tandem with the insertion of a gastric tube. The laryngeal cuff of LMA Protector™ allows a large catchment reservoir in the event of gastric content aspiration.

Methods
We evaluated the performance characteristics of the LMA Protector™ in 30 unparalysed, moderately obese patients. First attempt insertion rate, time for insertion, oropharyngeal leak pressure (OLP), and incidence of complications were recorded.

Results
We found high first and second attempt insertion rates of 28(93%) and 1(33%) respectively, with one failed attempt where no capnography trace could be detected, presumably from a downfolded device tip. The LMA Protector™ was inserted rapidly in 21.0(4.0) seconds and demonstrated high OLP of 31.8(5.4) cmH2O. Fibreoptic assessment showed a clear view of vocal cords in 93%. The incidence of blood staining on removal of device was 48%, postoperative sore throat 27%, dysphagia 10% and dysphonia 20% (all self-limiting, resolving a few hours postoperatively).

Conclusions
We conclude that the LMA Protector™ was associated with easy, expedient first attempt insertion success, demonstrating high oropharyngeal pressures and good anatomical position in the moderately obese population, with relatively low postoperative airway morbidity.

Trial registration
Australian New Zealand Clinical Trials Registry, ACTRN12617001152314. Registered 7 August 2017.
The accuracy of ultrasound to predict endotracheal tube size for pediatric patients with congenital scoliosis
Authors: Hao Jianhong , Zhang Jie , Dong Buhuai , Luo Zhenguo 
Published: July 2020

AbstractBackgroundUltrasonography has been used to predict the necessary endotracheal tube (ETT) size by measuring the cricoid cartilage diameter. The aim of this study was to determine the accuracy of ultrasound to predict ETT size for pediatric patients with congenital scoliosis.MethodsFifty pediatric patients who underwent scoliosis surgery were included in the study. According to the position of the scoliosis, patients were divided into three groups: Group C (cervical lateral bending), Group T (thoracic scoliosis), and Group L (lumbar scoliosis). For all participants, the transverse diameter of the cricoid cartilage was measured with ultrasonography. The initial ETT size was chosen according to the measurements, then the leak test was used to determine the best-fit ETT size. The ETT size predicted by ultrasound and the best-fit ETT size were compared using Bland-Altman analysis.ResultsThere was a strong correlation between the best-fit ETT size and the ETT size predicted by ultrasound in Group T (r = 0.93,p < 0.001) and Group L (r = 0.94,p < 0.001) and a moderate correlation in Group C (r = 0.83,p < 0.001). Bland-Altman analysis showed that the ETT size was overestimated by ultrasound in pediatric patients with cervical lateral bending (bias = 0.73 mm, precision = 0.42 mm, limit of agreement = 0.08 to 1.38 mm).ConclusionUltrasound is a reliable tool to predict ETT size for pediatric patients with thoracic or lumbar scoliosis. However, pediatric patients with cervical lateral bending will need an ETT smaller than the size predicted by ultrasonography.Trial registrationChinese Clinical Trial Registry, TRN:ChiCTR1900023408, date of registration: 05.26.2019, ‘retrospectively registered’.
Comparison of end-to-side hand-sewn and side-to-side stapled cervical esophagogastric anastomosis in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy: an Iranian retrospective cohort study
Authors: Rasihashemi Seyed Ziaeddin , Ramouz Ali , Beheshtirouy Samad , Amini Hassan 
Published: July 2020

Abstract
Background
Controversies in terms of efficacy and postoperative advantages surround stapled esophagogastric anastomosis compared with the hand-sewn technique as a treatment for patients with esophageal cancer. The purpose of this study was to compare the clinical outcomes of hand-sewn end-to-side esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis after esophagectomy for the aforementioned patients.

Methods
This retrospective cohort study involved examining the medical records of 433 patients who underwent transhiatal esophagectomy for esophageal cancer from March 2010 to March 2016. All the patients were operated using end-to-side hand-sewn esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis. 409 of the patients received a year’s worth of follow-up evaluations. All the cases were revisited in 2 weeks as well as in four, eight, and 12 months after surgery. The patients were assessed in terms of postoperative outcomes, including reflux symptoms, anastomotic leakage and stricture, and the need for anastomotic dilatation.

Results
Hand-sewn anastomosis was carried out in 271 (62.5%) patients, whereas stapled anastomosis was performed in 162 (37.4%) patients. The mean operative times were 214.46 ± 84.33 min and 250.55 ± 43.31 min for the stapled and hand-sewn anastomosis groups, respectively (P = 0.028). The two groups showed no significant differences with respect to stays in intensive care units and hospitals. Postoperatively, 38 (14.67%) cases of anastomotic leakage were detected in the hand-sewn anastomosis group, with incidence being significantly higher than that in the stapled anastomosis group (8 cases or 5.33%; P = 0.002). Anastomotic stricture occurred less frequently in the patients who underwent stapled anastomosis (P = 0.004). Within the one-year follow-up period, the patients treated via hand-sewn anastomosis more frequently required anastomotic dilatation (P = 0.02).

Conclusion
Side-to-side stapled cervical esophagogastric anastomosis may reduce operation times and decrease the rates of anastomotic leakage, anastomotic stricture, and anastomotic dilatation in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy.
Determine TB-LAM point-of-care tuberculosis assay predicts poor outcomes in outpatients during their first year of antiretroviral therapy in South Africa
Authors: Kerkhoff Andrew D. , Longley Nicky , Kelly Nicola , Cross Anna , Vogt Monica , Wood Robin , Hermans Sabine , Lawn Stephen D. , Harrison Thomas S. 
Published: July 2020

Abstract
Background
Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART.

Methods
Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at  three months and one year of follow-up.

Results
468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive – including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9–7.1) and 2.6 (95%, 1.2–5.7), respectively.

Conclusions
Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART.
High fecal carriage of extended Beta Lactamase producing Enterobacteriaceae among adult patients admitted in referral hospitals in Dar es Salaam, Tanzania
Authors: Kibwana Upendo O. , Majigo Mtebe , Kamori Doreen , Manyahi Joel 
Published: July 2020

Abstract
Background
Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam.

Methods
This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 μg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20.

Results
Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07–69.88, p = 0.01).

Conclusions
High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.
Development and validation of a scoring system for predicting cancer patients at risk of extended-spectrum b-lactamase-producing Enterobacteriaceae infections
Authors: Martínez-Valencia Alvaro J. , Gómez Martínez Brian J. , Montañez Ayala Anita M. , García Katherin , Sánchez Pedraza Ricardo , Jiménez Cetina Leydy P. , Gómez Rincón Julio C. , Cuervo Maldonado Sonia I. 
Published: July 2020

AbstractBackgroundExtended-spectrum beta-lactamase producingEnterobacteriaceae(ESBL-PE) infections are frequent and highly impact cancer patients. We developed and validated a scoring system to identify cancer patients harboring ESBL-PE at the National Institute of Cancer of Colombia.MethodsWe retrospectively analyzed medical records of 1695 cancer patients. Derivation phase included 710 patients admitted between 2013 to 2015, ESBL-PE positive culture (n = 265) paired by month and hospitalization ward with Non-ESBL-PE (n = 445). A crude and weighted score was developed by conditional logistic regression. The model was evaluated in a Validation cohort (n = 985) with the same eligibility criteria between 2016 to 2017.ResultsThe score was based on eight variables (reported with Odds Ratio and 95% confidence interval): Hospitalization ≥7 days (5.39 [2.46–11.80]), Hospitalization during the previous year (4, 87 [2.99–7.93]), immunosuppressive therapy during the previous 3 months (2.97 [1.44–6.08]), Neutropenia (1.90 [1.12–3.24]), Exposure to Betalactams during previous month (1.61 [1.06–2.42]), Invasive devices (1.51 [1.012–2.25]), Neoplasia in remission (2.78 [1.25–1.17]), No chemotherapy during the previous 3 months (1.90 [1.22–2.97]). The model demonstrated an acceptable discriminatory capacity in the Derivation phase, but poor in the Validation phase (Recipient Operating Characteristic Curve: 0.68 and 0.55 respectively).ConclusionsCancer patients have a high prevalence of risk factors for ESBL-PE infection. The scoring system did not adequately discriminate patients with ESBL-PE. In a high-risk population, other strategies should be sought to identify patients at risk of resistant ESBL-PE infection.
Nephrotic-range proteinuria and central nervous involvement in typical hemolytic uremic syndrome: a case report
Authors: Shi Chuan , Li Chao , Ye Wei , Ye Wen-ling , Li Ming-xi 
Published: July 2020

Abstract
Background
Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs.

Case presentation
A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset.

Conclusion
We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome.
Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia
Authors: Vásquez A. M. , Vélez G. , Medina A. , Serra-Casas E. , Campillo A. , Gonzalez I. J. , Murphy S. C. , Seilie A. M. , Ding X. C. , Tobón Castaño A. 
Published: July 2020

Abstract
Background
In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women.

Methods
A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing.

Results
The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/μL).

Conclusions
There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated.

Trial registration
ClinicalTrials.gov, Identifier: NCT03172221, Date of registration: May 29, 2017.