bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma
Authors: Borgatti Antonella , Fieberg Ann , Winter Amber L. , Stuebner Kathleen , Taras Elizabeth , Todhunter Deborah , Masyr Alison , Rendhal Aaron , Vallera Daniel A. , Koopmeiners Joseph S. , Modiano Jaime F.
Published: March 2020

We previously reported that eBAT, an EGF‐targeted angiotoxin, was safe and it improved the overall survival for dogs with splenic haemangiosarcoma when added to the standard of care in a single cycle of three administrations in the minimal residual disease setting. Our objective for the SRCBST‐2 trial was to assess whether increased dosing through multiple cycles of eBAT would be well tolerated and would further enhance the benefits of eBAT. Eligibility was expanded to dogs with stage 3 haemangiosarcoma, provided that gross lesions could be surgically excised. The interval between eBAT and the start of chemotherapy was reduced, and the experimental therapy was expanded to three cycles, each administered at the biologically active dose (50 μg/kg) on a Monday/Wednesday/Friday schedule following splenectomy, and scheduled 1 week prior to the first, second and fifth doxorubicin chemotherapy. Twenty‐five dogs were enrolled; six experienced acute hypotension with two requiring hospitalization. Self‐limiting elevation of ALT was observed in one dog. A statistically significant survival benefit was not seen in this study in eBAT‐treated dogs compared with a Contemporary comparison group of dogs with stages 1‐3 haemangiosarcoma treated with standard of care alone. Our results indicate that repeated dosing cycles of eBAT starting 1 week prior to doxorubicin chemotherapy led to greater toxicity and reduced efficacy compared with a single cycle given between surgery and a delayed start of chemotherapy. Further work is needed to understand the precise mechanisms of action of eBAT in order to optimize its clinical benefits in the treatment of canine haemangiosarcoma and other tumours. IACUC Protocols 1110A06186 and 1507‐32804A.
The Sustainability Issue; What Meaning for the Economic and Human Activity?
Authors: COSSIGA Giovanni Antonio
Published: March 2020

The sustainability issue, understood as a good relationship between humankind and nature, can offer the opportunity to analyze certain aspects of the economic theory. If we admit that the stability in economy is a natural condition for linear growth and instead the conjuncture is a trouble for growth due to the loss of natural balance, some consequences will follow. The long fight against instability has not been won, always struggling between inflation and deflation. It follows that the fight against inflation first and then deflation couldn’t counter the real malaise of the global economy: the instability. That is the deviation of economic systems from the natural path of balance with nature. Therefore, the results obtained struggling with monetary alterations, although significant, would be temporary and unable to solve the core of the matter. It follows that the economic support policies have essentially addressed the formal aspect, I would say just indicative of the imbalance, without obtaining stable results in the natural balance recovery. From this point of view, the interventions of fiscal policy, despite some good tests obtained by trying to reduce the strength of the 2008-2010 financial crisis, have not solved however the poisonous aftermath of deflation. Moreover, during the last decade, the health of global economic systems has always required, to be maintained, a defense in the form of supporting policies through neo-Keynesian interventions. And not only that. Because the monetary policy used all its weapons, even unconventional ones, to defeat deflation: nonetheless, it didn’t achieve anything but just a mitigation of phenomena. Always provided, anyway, that the wave of new liquidity continues, as requested by the markets. The point is therefore which is the exit strategy from this situation, considering that the progressive exhaustion of the resources of fiscal and monetary policies sets the expectation of a potential progressive recession on a global basis. Well, according to the sustainability theory the recession is not a bad thing in itself, but it’s rather a cure whose impact we must learn to measure, having the view to mitigate the most negative social effects.
Payment Delays and Financial Performance of Construction Firms in Vihiga County, Kenya
Authors: Kalegera Brenda Ajema , Omoro Nixon Oluoch
Published: March 2020

The purpose of this study was to establish whether payment delays affect financial performance of construction firms. The study employed cross sectional research design, stratified simple random sampling and census survey of 32 construction firms. The study relied on secondary data from audited financial reports. Data was analyzed using both descriptive and inferential statistics - multivariate analysis. There was no statistical significant effect between delayed payments and financial performance as measured by Net profit margin and current ratio, probably other factors or measures such as management style and strategies could have affected the two variables. Our conclusion however, is that late payments in commercial transactions by the public or generations  and private entities have detrimental effects on the business environment,  especially by exacerbating the burden of already financially constrained firms which can ultimately push them out of business. The study was only limited to one financial year and construction firm.
Phonation threshold pressure using a 3-mass model of phonation with empirical pressure values
Authors: Perrine Brittany L. , Scherer Ronald C. , Fulcher Lewis P. , Zhai Guangnian
Published: March 2020

Understanding the control parameters that influence phonation threshold pressure can have important implications for ease of phonation. Using a computer model of phonation can aid in studying parameters not easily controllable through human experimental work and may provide a means of explaining variations seen across human participants. A vertical 3-mass computer model of phonation with empirical driving pressures was used to obtain phonation threshold pressures for a variety of prephonatory conditions that may be realistically produced by humans. The resulting phonation threshold pressures are reasonable compared to results from human studies and may extend beyond the range of phonatory control parameters studied in human experiments. In addition, the present work adds a formula for calculating phonation threshold pressure based on the prephonatory glottal angle, the tension of the vocal folds, and the prephonatory diameter. Of special interest is that, as the prephonatory angle of convergence increases from 0 degrees (the rectangular glottis condition), the phonation threshold pressure increases in a nearly linear fashion.
Influence of Maturation Status on Eccentric Hamstring Strength Improvements in Youth Male Soccer Players After the Nordic Hamstring Exercise
Authors: Drury Benjamin , Green Thomas , Ramirez-Campillo Rodrigo , Moran Jason
Published: March 2020

Purpose: This study examined the effects of a 6-week Nordic hamstring exercise (NHE) program in youth male soccer players of less mature (pre–peak height velocity [PHV]) or more mature (mid/post-PHV) status. Methods: Forty-eight participants were separated into pre-PHV (11.0 [0.9] y) or mid/post-PHV (13.9 [1.1]) groups and further divided into experimental (EXP) and control groups with eccentric hamstring strength assessed (NordBord) both before and after the training program. Participants in the EXP groups completed a periodized NHE program performed once or twice weekly over a 6-week period. Results: The NHE program resulted in moderate and small increases in relative eccentric hamstring strength (in newtons per kilogram) in the pre-PHV EXP (d = 0.83 [0.03–1.68]) and mid-PHV EXP (d = 0.53 [−0.06 to 1.12]) groups, respectively. Moderate increases in the same measure were also seen in the between-groups analyses in the pre-PHV (d = 1.03 [0.23–1.84]) and mid-PHV (d = 0.87 [0.22–1.51]) groups, with a greater effect observed in the former. Conclusion: The results from this study demonstrate that a 6-week NHE program can improve eccentric hamstring strength in male youth soccer players, with less-mature players achieving mostly greater benefits. The findings from this study can aid in the training prescription of NHE in youth male soccer players.
A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer
Authors: Ni Qianqian , Zhang Fuwu , Liu Yijing , Wang Zhantong , Yu Guocan , Liang Brian , Niu Gang , Su Ting , Zhu Guizhi , Lu Guangming , Zhang Longjiang , Chen Xiaoyuan
Published: March 2020

A rationally designed bi-adjuvant nanovaccine enhances neoantigen immunogenicity and enables combination immunotherapy.
Distinguishing cell phenotype using cell epigenotype
Authors: Wytock Thomas P. , Motter Adilson E.
Published: March 2020

Gene expression and chromatin conformation reliably distinguish cell types, enabling equation-free control of human cells.
Verification of extreme event attribution: Using out-of-sample observations to assess changes in probabilities of unprecedented events
Authors: Diffenbaugh Noah S.
Published: March 2020

Using out-of-sample observations to verify extreme event attribution results.
No evidence for DNA
N
6
-methyladenine in mammals
Authors: Douvlataniotis Karolos , Bensberg Maike , Lentini Antonio , Gylemo Björn , Nestor Colm E.
Published: March 2020

Technical errors have resulted in the false discovery of the DNA modification
N
6
-methyladenine in mammals.
A psychological stressor conveyed by appetite-linked neurons
Authors: Lee Eun Jeong , Hanchate Naresh K. , Kondoh Kunio , Tong Ai Phuong S. , Kuang Donghui , Spray Andrew , Ye Xiaolan , Buck Linda B.
Published: March 2020

New studies show that POMC neurons linked to appetite suppression also play a key role in stress hormone responses.
National monuments and economic growth in the American West
Authors: Walls Margaret , Lee Patrick , Ashenfarb Matthew
Published: March 2020

Protecting public lands as national monuments in the western United States is more help than hindrance to local economies.
Nanobiohybrids: Materials approaches for bioaugmentation
Authors: Guo Ziyi , Richardson Joseph J. , Kong Biao , Liang Kang
Published: March 2020

We review recent advances and prospects of interfacing functional nanomaterials with biological systems for nanobiohybrids.
Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala
Authors: Khom S. , Steinkellner T. , Hnasko T. S. , Roberto M.
Published: March 2020

Alcohol dependence induces hypersensitivity of the SP/NK-1R system and its regulation of CeA inhibitory transmission.
Mediterranean radiocarbon offsets and calendar dates for prehistory
Authors: Manning Sturt W. , Kromer Bernd , Cremaschi Mauro , Dee Michael W. , Friedrich Ronny , Griggs Carol , Hadden Carla S.
Published: March 2020

Intra-annual offsets in Northern Hemisphere atmospheric radiocarbon levels challenge and complicate Old World radiocarbon dating.
10,000 social brains: Sex differentiation in human brain anatomy
Authors: Kiesow Hannah , Dunbar Robin I. M. , Kable Joseph W. , Kalenscher Tobias , Vogeley Kai , Schilbach Leonhard , Marquand Andre F. , Wiecki Thomas V. , Bzdok Danilo
Published: March 2020

Population variability in social lifestyle is reflected in brain morphology in sex-dependent ways.
TRPC1 participates in the HSV-1 infection process by facilitating viral entry
Authors: He DongXu , Mao AiQin , Li YouRan , Tam SiuCheung , Zheng YongTang , Yao XiaoQiang , Birnbaumer Lutz , Ambudkar Indu S. , Ma Xin
Published: March 2020

TRPC1 channel facilitates virus infection.
Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease
Authors: Manso Ana Maria , Hashem Sherin I. , Nelson Bradley C. , Gault Emily , Soto-Hermida Angel , Villarruel Elizza , Brambatti Michela , Bogomolovas Julius , Bushway Paul J. , Chen Chao , Battiprolu Pavan , Keravala Annahita , Schwartz Jonathan D. , Shah Gaurav , Gu Yusu , Dalton Nancy D. , Hammond Kirk , Peterson Kirk , Saftig Paul , Adler Eric D.
Published: March 2020

AAV9.LAMP2B corrects metabolic and physiologic manifestations of a murine model of Danon disease.
Strong vaccine responses during chemotherapy are associated with prolonged cancer survival
Authors: Melief Cornelis J. M. , Welters Marij J. P. , Vergote Ignace , Kroep Judith R. , Kenter Gemma G. , Ottevanger Petronella B. , Tjalma Wiebren A. A. , Denys Hannelore , van Poelgeest Mariette I. E. , Nijman Hans W. , Reyners Anna K. L. , Velu Thierry , Goffin Frederic , Lalisang Roy I. , Loof Nikki M. , Boekestijn Sanne , Krebber Willem Jan , Hooftman Leon , Visscher Sonja , Blumenstein Brent A. , Stead Richard B. , Gerritsen Winald , van der Burg Sjoerd H.
Published: March 2020

A strong vaccine-induced T cell response during standard-of-care chemotherapy correlates with survival in patients with advanced cervical cancer.
Proteome of a Moraxella catarrhalis Strain under Iron-Restricted Conditions
Authors: Blakeway Luke V. , Tan Aimee , Peak Ian R. , Atack John M. , Seib Kate L.
Published: March 2020

Moraxella catarrhalis
is a leading cause of otitis media and exacerbations of chronic obstructive pulmonary disease; however, its response to iron starvation during infection is not completely understood. Here, we announce a sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) data set describing the differential expression of the
M. catarrhalis
CCRI-195ME proteome under iron-restricted versus iron-replete conditions.
Analysis of the Microbiome of Rainbow Trout (Oncorhynchus mykiss) Exposed to the Pathogen Flavobacterium psychrophilum 10094
Authors: Valdés Natalia , Gonzalez Alex , Garcia Veronica , Tello Mario
Published: March 2020

Rainbow trout that were resistant or susceptible to
Flavobacterium psychrophilum
infection were compared with respect to their microbial composition by using 16S rRNA V3-V4 sequencing. The differences occurred in gills, where resistant fish displayed a greater abundance of the phylum
Proteobacteria
and a smaller proportion of
Firmicutes
relative to those of susceptible fish.
Draft Genome Sequence of the Strawberry Anthracnose Pathogen
Colletotrichum fructicola
Authors: Armitage Andrew D. , Nellist Charlotte F. , Bates Helen J. , Zhang Liqing , Zou Xiaohua , Gao Qing-Hua , Harrison Richard J.
Published: March 2020

Colletotrichum fructicola
is a causal agent of strawberry anthracnose and a major economic pathogen of horticultural and ornamental crops worldwide. Here, we present an annotated draft genome sequence for a
C. fructicola
isolate previously used for transcriptomic analysis. The assembly totals 58.0 Mb in 477 contigs with 18,143 predicted genes.
Hybrid turbidite-drift channel complexes: An integrated multiscale model
Authors: Fuhrmann A. , Kane I.A. , Clare M.A. , Ferguson R.A. , Schomacker E. , Bonamini E. , Contreras F.A.
Published: March 2020

The interaction of deep-marine bottom currents with episodic, unsteady sediment gravity flows affects global sediment transport, forms climate archives, and controls the evolution of continental slopes. Despite their importance, contradictory hypotheses for reconstructing past flow regimes have arisen from a paucity of studies and the lack of direct monitoring of such hybrid systems. Here, we address this controversy by analyzing deposits, high-resolution seafloor data, and near-bed current measurements from two sites where eastward-flowing gravity flows interact(ed) with northward-flowing bottom currents. Extensive seismic and core data from offshore Tanzania reveal a 1650-m-thick asymmetric hybrid channel levee-drift system, deposited over a period of ∼20 m.y. (Upper Cretaceous to Paleocene). High-resolution modern seafloor data from offshore Mozambique reveal similar asymmetric channel geometries, which are related to northward-flowing near-bed currents with measured velocities of up to 1.4 m/s. Higher sediment accumulation occurs on the downstream flank of channel margins (with respect to bottom currents), with inhibited deposition or scouring on the upstream flank (where velocities are highest). Toes of the drift deposits, consisting of thick laminated muddy siltstone, which progressively step back into the channel axis over time, result in an interfingering relationship with the sandstone-dominated channel fill. Bottom-current flow directions contrast with those of previous models, which lacked direct current measurements or paleoflow indicators. We finally show how large-scale depositional architecture is built through the temporally variable coupling of these two globally important sediment transport processes. Our findings enable more-robust reconstructions of past oceanic circulation and diagnosis of ancient hybrid turbidite-drift systems.
Subtle neuropsychiatric symptoms of glioblastoma multiforme misdiagnosed as depression
Authors: Leo Raphael Jerome , Frodey Jill N , Ruggieri Matthew L
Published: March 2020

Glioblastoma multiforme (GBM) is the most common of the aggressive primary brain tumours arising in adults and has a dire prognosis. Neuropsychiatric symptoms can vary significantly among afflicted persons; psychiatric disturbances may be the predominant presenting symptoms. Distinguishing between functional psychiatric disorders, particularly depression, from other subtle neuropsychiatric disturbances that may accompany GBM can be challenging. The authors present a clinical case and review of the literature in an attempt to highlight the special considerations that should be taken into account when evaluating patients who present with late-onset or atypical symptoms, refractory psychiatric symptoms, or subtle neurological disturbances signalling the need for diagnostic assessment, particularly neuroimaging, for the presence of a tumour. Early diagnosis is critical for improvement in quality of life.
SpontaneousBacteroides fragilisspondylodiscitis in an elderly lady
Authors: Weinberg Sharon Esther , Tabet Patrick Paul , McGregor Claire Elizabeth , Arvidsson Alice Maria
Published: March 2020

A 76-year-old woman presented following two episodes of unexplained falls at home. Blood cultures were positive forBacteroides fragilisand following investigations she was diagnosed with L4/L5 spondylodiscitis confirmed on spine MRI. She was initially treated with intravenous metronidazole and flucloxacillin prior to switching to ceftriaxone with good results. No primary cause ofB. fragilisbacteraemia was found in this case.B. fragilisis a rare cause of spondylodiscitis.
Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism
Authors: Green Charlotte J , Pramfalk Camilla , Charlton Catriona A , Gunn Pippa J , Cornfield Thomas , Pavlides Michael , Karpe Fredrik , Hodson Leanne
Published: March 2020

Objective

Increased hepatic de novo lipogenesis (DNL) is suggested to be an underlying cause in the development of nonalcoholic fatty liver disease and/or insulin resistance. It is suggested that omega-3 fatty acids (FA) lower hepatic DNL. We investigated the effects of omega-3 FA supplementation on hepatic DNL and FA oxidation using a combination of human in vivo and in vitro studies.

Research design and methods

Thirty-eight healthy men were randomized to take either an omega-3 supplement (4 g/day eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) as ethyl esters) or placebo (4 g/day olive oil) and fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on intrahepatocellular triacylglycerol (IHTAG) content, hepatic DNL and FA oxidation were investigated using metabolic substrates labeled with stable-isotope tracers. In vitro studies, using a human liver cell-line was undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs.

Results

Fasting plasma TAG concentrations significantly decreased in the omega-3 group and remained unchanged in the placebo group. Eight weeks of omega-3 supplementation significantly decreased IHTAG, fasting and postprandial hepatic DNL while significantly increasing dietary FA oxidation and fasting and postprandial plasma glucose concentrations. In vitro studies supported the in vivo findings of omega-3 FAs (EPA+DHA) decreasing intracellular TAG through a shift in cellular metabolism away from FA esterification toward oxidation.

Conclusions

Omega-3 supplementation had a potent effect on decreasing hepatic DNL and increasing FA oxidation and plasma glucose concentrations. Attenuation of hepatic DNL may be considered advantageous; however, consideration is required as to what the potential excess of nonlipid substrates (eg, glucose) will have on intrahepatic and extrahepatic metabolic pathways.

Trial registration number

NCT01936779.
Lessons from developing, implementing and sustaining a participatory partnership for children’s surgical care in Tanzania
Authors: Philipo Godfrey Sama , Nagraj Shobhana , Bokhary Zaitun M , Lakhoo Kokila
Published: March 2020

Global surgery is an essential component of Universal Health Coverage. Surgical conditions account for almost one-third of the global burden of disease, with the majority of patients living in low-income and middle-income countries (LMICs). Children account for more than half of the global population; however, in many LMIC settings they have poor access to surgical care due to a lack of workforce and health system infrastructure to match the need for children’s surgery. Surgical providers from high-income countries volunteer to visit LMICs and partner with the local providers to deliver surgical care and trainings to improve outcomes. However, some of these altruistic efforts fail. We aim to share our experience on developing, implementing and sustaining a partnership in global children’s surgery in Tanzania. The use of participatory methods facilitated a successful 17-yearlong partnership, ensured a non-hierarchical environment and encouraged an understanding of the context, local needs, available resources and hospital capacity, including budget constraints, when codesigning solutions. We believe that participatory approaches are feasible and valuable in developing, implementing and sustaining global partnerships for children’s surgery in LMICs.
Sustaining improved nutritional support for very low birthweight infants
Authors: Kresch Mitchell , Mehra Kashish , Jack Richard , Greecher Coleen
Published: March 2020

Background

Postnatal growth failure (PGF) in very low birthweight (VLBW) infants is a result of factors such as prematurity, acute illness and suboptimal nutritional support. Before this project began, 84% of appropriately grown VLBW infants in our neonatal intensive care unit experienced PGF. The aims of this quality improvement project were to reduce the percentage of infants discharged with PGF to less than 50% within 2 years and to maintain a rate of PGF under 50%.

Methods

All inborn VLBW infants were eligible for this study. Infants with congenital anomalies were excluded. We determined key drivers for optimal nutrition and identified potentially better practices (process measures) based on a review of the literature, which included more rapid initiation of starter total parenteral nutrition (TPN), aggressive use and advancement of regular TPN, and fortification of human milk when the volume of intake reached 80 mL/kg/day. Three Plan-Do-Study-Act (PDSA) cycles were tested.

Results

Time to initiation of starter TPN was significantly reduced from 5.5 hours to under 3 hours. Regular TPN provided the goals for amino acids and lipids at increased frequency after the first two PDSA cycles. The proportion of infants whose milk was fortified at 80 mL/kg/day increased after the third PDSA cycle.

Conclusions

We found a sustained decrease in the percentage of infants discharged with PGF from 84% at baseline to fewer than 50% beginning in 2010–2011 through 2016, with 23.1% of infants experiencing PGF in 2016. We have achieved improved nutritional support for VLBW infants using the model for improvement.
Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015
Authors: LeBlanc Jason , ElSherif May , Ye Lingyun , MacKinnon-Cameron Donna , Ambrose Ardith , Hatchette Todd F , Lang Amanda LS , Gillis Hayley D , Martin Irene , Demczuk Walter H , LaFerriere Craig , Andrew Melissa K , Boivin Guy , Bowie William , Green Karen , Johnstone Jennie , Loeb Mark , McCarthy Anne , McGeer Allison , Semret Makeda , Trottier Sylvie , Valiquette Louis , Webster Duncan , McNeil Shelly A
Published: March 2020

Background

In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age.

Methods

Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16–49, 50–64, ≥65 and ≥50 years).

Results

Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively.

Conclusions

Adults hospitalised with pCAP in the age cohort of 50–64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.
Patient with frontal-variant syndrome in early-onset Alzheimer's disease
Authors: Cai Han , Ning Su , Li Wei , Li Xia , Xiao Shifu , Sun Lin
Published: March 2020

The clinical manifestation of frontal-variant Alzheimer’s disease (fvAD) is not typical, and it is difficult yet necessary to differentiate fvAD from frontal-variant frontal temporal dementia (fvFTD). We describe a patient with early-onset Alzheimer’s disease (AD) who presented with an fvFTD-like syndrome and apolipoprotein E ɛ3/ ɛ4 genotype. A brain amyloid imaging procedure, 11C-Pittsburgh compound B positron emission tomography (PET), supported the final diagnosis of AD. Our present case highlights the clinical variability that characterises early-onset AD. A multimodal approach is crucial when assessing rare forms of dementia.
Prognostic value of von Willebrand factor in adult patients with congenital heart disease
Authors: Ohuchi Hideo , Hayama Yohsuke , Miike Hikari , Suzuki Dai , Nakajima Kimiko , Iwasa Toru , Konagai Nao , Sakaguchi Heima , Miyazaki Aya , Shiraishi Isao , Kurosaki Ken-ichi , Nakai Michikazu
Published: March 2020

Objectives

von Willebrand factor (vWF) has prognostic value in patients with heart failure (HF) and in those with liver disease. Liver congestion, due to right-sided HF (RHF), is one of the major clinical pathophysiologic manifestations in adults with congenital heart disease (ACHD). The present study’s purpose was to clarify the prognostic value of plasma levels of vWF antigen (vWF:Ag) in ACHD.

Methods

We measured vWF:Ag (%) in 382 consecutive patients (20 unrepaired cyanotic ACHD, 172 Fontan patients and 190 ACHD after biventricular repair) and compared the results with the clinical profiles and prognosis.

Results

The plasma vWF:Ag level was 130±53 (normal range: 55%–190%), and 48 patients (13%) showed high levels of vWF:Ag (≥190%). Older age, Fontan circulation, higher central venous pressure, lower arterial oxygen saturation and lower plasma levels of albumin were independently associated with high log (vWF:Ag) (p<0.05–0.0001). During the follow-up of 2.4±1.4 years, 15 patients died. High log (vWF:Ag) predicted the all-cause mortality (HR 1.63 per 0.1, 95% CI 1.40 to 1.96, p<0.0001). Specifically, patients with high vWF:Ag (≥165%) had a substantially higher risk of all-cause mortality (HR 56.4, 95% CI 11.4 to 1020, p<0.0001), and this prognostic value was independent of plasma levels of brain-type natriuretic peptide.

Conclusions

High vWF:Ag may reflect RHF severity and related liver dysfunction with a strong prognostic value of all-cause mortality in ACHD. Thus, vWF:Ag might be an excellent biomarker for monitoring ACHD with RHF.
Phase II study of α-galactosylceramide-pulsed antigen-presenting cells in patients with advanced or recurrent non-small cell lung cancer
Authors: Toyoda Takahide , Kamata Toshiko , Tanaka Kazuhisa , Ihara Fumie , Takami Mariko , Suzuki Hidemi , Nakajima Takahiro , Ikeuchi Takayuki , Kawasaki Yohei , Hanaoka Hideki , Nakayama Toshinori , Yoshino Ichiro , Motohashi Shinichiro
Published: March 2020

Background

Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by αGalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events. Based on these results, we performed a phase II trial to evaluate clinical responses, safety profiles and immune responses as a second-line treatment for advanced NSCLC.

Methods

Patients with advanced or recurrent NSCLC refractory to first-line chemotherapy were eligible. αGalCer-pulsed APCs were intravenously administered four times. Overall survival time was evaluated as the primary endpoint. The safety profile and immune responses after APC injection were also monitored. This study was an open label, single-arm, phase II clinical trial performed at Chiba University Hospital, Japan.

Results

Thirty-five patients were enrolled in this study, of which 32 (91.4%) completed the trial. No severe adverse events related to the treatment were observed. The estimated median survival time of the 35 cases was 21.9 months (95% CI, 14.8 to 26.0). One case (2.9%) showed a partial response, 14 cases (40.0%) remained as stable disease, and 19 cases (54.3%) were evaluated as progressive disease. The geometric mean number of iNKT cells in all cases was significantly decreased and the mean numbers of natural killer (NK) cells, interferon-γ-producing cells in response to αGalCer, and effector CD8+ T cells were significantly increased after the administration of αGalCer-pulsed APCs.

Conclusions

The intravenous administration of αGalCer-pulsed APCs was well-tolerated and was accompanied by prolonged overall survival. These results are encouraging and warrant further evaluation in a randomized phase III trial to demonstrate the survival benefit of this immunotherapy.

Trial registration number

UMIN000007321.
Phase 2 study of pembrolizumab in patients with advanced rare cancers
Authors: Naing Aung , Meric-Bernstam Funda , Stephen Bettzy , Karp Daniel D , Hajjar Joud , Rodon Ahnert Jordi , Piha-Paul Sarina A , Colen Rivka R , Jimenez Camilo , Raghav Kanwal P , Ferrarotto Renata , Tu Shi-Ming , Campbell Matthew , Wang Linghua , Sabir Sarjeel H , Tapia Coya , Bernatchez Chantale , Frumovitz Michael , Tannir Nizar , Ravi Vinod , Khan Saria , Painter Jeane M , Abonofal Abulrahman , Gong Jing , Alshawa Anas , McQuinn Lacey M , Xu Mingxuan , Ahmed Sara , Subbiah Vivek , Hong David S , Pant Shubham , Yap Timothy A , Tsimberidou Apostolia M , Dumbrava Ecaterina E Ileana , Janku Filip , Fu Siqing , Simon Richard M , Hess Kenneth R , Varadhachary Gauri R , Amir Habra Mouhammed
Published: March 2020

Background

Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.

Methods

In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).

Results

A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma–pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.

Conclusions

The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma–pheochromocytoma supports further evaluation of pembrolizumab in this patient population.

Trial registration number

NCT02721732
Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis
Authors: Yousufuddin Mohammed , Zhu Ye , Al Ward Ruaa , Peters Jessica , Doyle Taylor , Jensen Kelsey L , Wang Zhen , Murad Mohammad Hassan
Published: March 2020

Objectives

The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival.

Methods

Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2).

Results

In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58–0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups.

Conclusions

In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.
Isolated surgical tricuspid repair versus replacement: meta-analysis of 15 069 patients
Authors: Wang Tom Kai Ming , Griffin Brian P , Miyasaka Rhonda , Xu Bo , Popovic Zoran B , Pettersson Gosta B , Gillinov Alan Marc , Desai Milind Y
Published: March 2020

Objectives

Tricuspid valve disease is increasingly encountered, but surgery is rarely performed in isolation, in part because of a reported higher operative risk than other single-valve operations. Although guidelines recommend valve repair, there is sparse literature for the optimal surgical approach in isolated tricuspid valve disease. We performed a meta-analysis examining outcomes of isolated tricuspid valve repair versus replacement.

Methods

We searched Pubmed, Embase, Scopus and Cochrane from January 1980 to June 2019 for studies reporting outcomes of both isolated tricuspid valve repair and replacement, excluding congenital tricuspid aetiologies. Data were extracted and pooled using random-effects models and Review Manager 5.3 software.

Results

There were 811 article abstracts screened, from which 52 full-text articles reviewed and 16 studies included, totalling 6808 repairs and 8261 replacements. Mean age ranged from 36 to 68 years and females made up 24%–92% of these studies. Pooled operative mortality rates and odds ratios (95% confidence intervals) for isolated tricuspid repair and replacement surgery were 8.4% vs 9.9%, 0.80 (0.64 to 1.00). Tricuspid repair was also associated with lower in-hospital acute renal failure 12.4% vs 15.6%, 0.82 (0.72 to 0.93) and pacemaker implantation 9.4% vs 21.0%, 0.37 (0.24 to 0.58), but higher stroke rate 1.5% vs 0.9%, 1.63 (1.10 to 2.41). There were no differences in rates of prolonged ventilation, mediastinitis, return to operating room or late mortality.

Conclusion

Isolated tricuspid valve repair was associated with significantly reduced in-hospital mortality, renal failure and pacemaker implantation compared with replacement and is therefore recommended where feasible for isolated tricuspid valve disease, although its higher stroke rate warrants further research.
Death in low-risk cardiac surgery revisited
Authors: Lidén Katarina , Ivert Torbjörn , Sartipy Ulrik
Published: March 2020

Background

A systematic review of low-risk death has been shown successful in identifying system weaknesses. The aim was to analyse early mortality in low-risk patients undergoing cardiac surgery and to determine the cause of death, classify if they were unavoidable or potentially preventable as a result of technical or system errors.

Methods

We included all low-risk patients who underwent cardiac surgery at our institution from 1 September 2009 to 31 August 2019. In patients operated between 2009 and 2011, we defined low risk as an additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) I less than or equal to 3, and from 2012 and onwards as a EuroSCORE II less than or equal to 1.5. The medical records for the patients who died within 30 days of surgery were thoroughly examined and the cause of death was classified as cardiac or non-cardiac. Furthermore, deaths were categorised as not preventable, preventable (technical error) or preventable (system error).

Results

During the study period 3103 low-risk patients underwent surgery, and 11 patients died within 30 days of the operation (0.35%). Six of these (55%) were classified as preventable and five non-preventable. Four of the preventable deaths were classified as technical errors and two were due to system errors.

Conclusions

A repeated systematic review of deaths in patients with a low preoperative risk showed that a majority of deaths were preventable, and therefore potentially avoidable. Similar to the previous assessment at our unit, mortality was very low and failure to communicate remains a modifiable factor that should be addressed.
Scattering of a Klein–Gordon particle by a smooth barrier
Authors: López Eduardo , Rojas Clara
Published: March 2020

We present a study of the one-dimensional Klein–Gordon equation by a smooth barrier. The scattering solutions are given in terms of the Whittaker Mκ,μ(x) function. The reflection and transmission coefficients are calculated in terms of the energy, the height, and the smoothness of the potential barrier. For any value of the smoothness parameter we observed transmission resonances.
Statefinder diagnosis for Tsallis agegraphic dark energy model with ωD − ωD′ pair
Authors: Srivastava Shikha , Dubey Vipin Chandra , Sharma Umesh Kumar
Published: March 2020

A new class of dark energy model, known as “Tsallis agegraphic dark energy (TADE),” has been proposed using the holographic principle and Tsallis nonextensive entropy (Mod. Phys. Lett. A, 2019), considering the conformal time as well as the age of the Universe as IR cutoffs in flat Universe. The trajectories for evolution of statefinder parameters in [Formula: see text], [Formula: see text], [Formula: see text] and the [Formula: see text] planes are plotted for the TADE 1 and TADE 2 models for the value of the Tsallis parameter [Formula: see text], and taking the TADE energy density parameter [Formula: see text], according to the Planck 2018 results VI — [Formula: see text]CDM observational data without interaction.
Synthesis and properties of low-crystallinity nylon 6 with high transparency and low hygroscopicity containing adipic acid
Authors: Lai Chiu-Chun , Yu Bo-Sien , Lo Hao-Wen , Teng Wei-Feng , Liu Lung-Chang , Chen Chien-Ming
Published: March 2020

In this research, a series of amorphous nylons 6 were prepared by introducing adipic acid and different structure amines into the copolymerization with caprolactam. The effects including thermal properties, crystallinity, dynamic mechanical properties, optical properties, and water absorption of different copolymerization structure and copolymerization ratio on the properties of nylon 6 were investigated. The results show the melting point and thermal cracking temperature Td 5 of nylon 6 are, respectively, between 179[Formula: see text]C and 217[Formula: see text]C and 278[Formula: see text]C to 336[Formula: see text]C. Nylon 6 structure introducing a methyl side chain is more effective than a meta-benzene ring, a meta-cycloalkyl, and bicycloalkyl groups, so CAMM and CAI have the lowest crystallinity.
POSTURAL STABILITY STRATEGIES IN TRANSTIBIAL AMPUTEES DURING QUIET STANDING IN ALTERED SENSORY CONDITIONS WEARING THREE TYPES OF PROSTHETIC FEET
Authors: ARIFIN NOORANIDA , ABU OSMAN NOOR AZUAN , ALI SADEEQ
Published: March 2020

Individuals with transtibial amputation exhibit altered movement strategy to sustain stability during quiet standing due to reduced proprioception on the amputated limb. The aim of this study is to determine the movement strategies in anterior–posterior and medial–lateral directions in predicting the overall postural stability. In this crossover study, postural stability of ten transtibial amputees was assessed using computed posturography while wearing different prosthetic foot types: solid ankle cushion heel (SACH), single axis (SA) and energy storage and return (ESAR). Three stability indices were measured during four conditions: standing with eyes opened and closed, standing on compliant surface and standing with tilted head. From the standard multiple regression analysis, 63% to 99% of the OSI score in all sensory conditions were explained from the MLSI score, while 11% to 56% from the APSI score. The Pearson’s [Formula: see text] indicated significant strong positive relationship between OSI and MLSI [Formula: see text]–[Formula: see text] during all sensory conditions. The APSI score was significantly lower than OSI during eyes-closed and head extended conditions for all prosthetic feet [Formula: see text]. Adjustments in postural stability strategies in transtibial amputees mostly occurred in medial–lateral direction regardless of prosthetic feet types and altered sensory conditions.
THEORETICAL ANALYSIS OF THE LEAKAGE THROUGH THE CEMENT LINE OF A SINGLE OSTEON
Authors: GAILANI GAFFAR , COWIN STEPHEN
Published: March 2020

This work focuses on the Lacunar–Canalicular Porosity (PLC) of cortical bone which includes the osteons. Osteons are semicylindrical porous structures saturated with fluid within the bone and are approximately 250[Formula: see text][Formula: see text]m in diameter. The outer boundary of the osteon is called the cement line. Some studies suggested that the cement line is less highly mineralized and produced evidence that it has less calcium and phosphorus and more sulfur than the neighboring bone lamellae. Most authors assume that the cement line is impermeable, while others assume that some canaliculi are crossing the cement line which will make it permeable to certain degree. The objective of this work is to develop a theoretical analysis to study the leakage through the cement line and its relationship with the pore pressure distribution. The theoretical analysis is developed using our previous analysis for osteon under harmonic loading with addition of leakage parameter. The leakage parameter varies from 0 to 1, where a value of 0 indicates free flow through the cement line and a value of 1 indicates no flow through the cement line. Experimental results could be compared to this developed theoretical solution to get in depth understanding of the effect of leakage on osteon poroelastic properties. Additionally, the developed theoretical solution will give insight into sensitivity of osteon pore pressure to leakage through the cement line.