bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Survival With Sebelipase Alfa Enzyme Replacement Therapy in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Final Results From 2 Open-Label Studies
Authors: Vijay Suresh , Brassier Anais , Ghosh Arunabha , Fecarotta Simona , Abel Florian , Marulkar Sachin , Jones Simon A. 
Published: September 2020

Abstract
Background: If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6 months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2/3 Survival of LAL-D Infants Treated With Sebelipase Alfa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa.Results: The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan-Meier estimates of survival to 12 months and 5 years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2 years in VITAL and 3.2 years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-age z scores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3–16.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7–19.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity.Conclusions: The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic, and liver parameters, and was generally well tolerated, with an acceptable safety profile.
Understanding the causes of errors in eukaryotic protein-coding gene prediction: a case study of primate proteomes
Authors: Meyer Corentin , Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie 
Published: September 2020

Abstract
Background. Recent advances in sequencing technologies have led to an explosion in the number of genomes available, but accurate genome annotation remains a major challenge. The prediction of protein-coding genes in eukaryotic genomes is especially problematic, due to their complex exon-intron structures. Even the best eukaryotic gene prediction algorithms can make serious errors that will significantly affect subsequent analyses. Results. We first investigated the prevalence of gene prediction errors in a large set of 176,478 proteins from ten primate proteomes available in public databases. Using the well-studied human proteins as a reference, a total of 82,305 potential errors were detected, including 44,001 deletions, 27,289 insertions and 11,015 mismatched segments where part of the correct protein sequence is replaced with an alternative erroneous sequence. We then focused on the mismatched sequence errors that cause particular problems for downstream applications. A detailed characterization allowed us to identify the potential causes for the gene misprediction in approximately half (5446) of these cases. As a proof-of-concept, we also developed a simple method which allowed us to propose improved sequences for 603 primate proteins. Conclusions. Gene prediction errors in primate proteomes affect up to 50% of the sequences. Major causes of errors include undetermined genome regions, genome sequencing or assembly issues, and limitations in the models used to represent gene exon-intron structures. Nevertheless, existing genome sequences can still be exploited to improve protein sequence quality. Perspectives of the work include the characterization of other types of gene prediction errors, as well as the development of a more comprehensive algorithm for protein sequence error correction.
Veno-venous-ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS
Authors: Qaqish Robert , Watanabe Yui , Galasso Marcos , Summers Cara , Ali Aadil , Takahashi Mamoru , Gazzalle Anajara , Liu Mingyao , Keshavjee Shaf , Cypel Marcelo , Sorbo Lorenzo Del 
Published: September 2020

Abstract
Background: There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods: Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized postinjury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n=5) or recruitment maneuvers alone (control, n=5) during ECMO.Results: PaO2/FiO2 after aspiration injury was 62.6 ±8 mmHg and 60.9 ±9.6 mmHg in the control and treatment group, respectively (p=0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions: A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
In vivo optical cellular diagnosis for uterine cervical or vaginal intraepithelial neoplasia using flexible gastrointestinal endocytoscopy -a prospective pilot study-
Authors: Ono Shoko , Nozaki Ayako , Matsuda Kana , Takakuwa Emi , Sakamoto Naoya , Watari Hidemichi 
Published: September 2020

Abstract
Background For patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy.Methods Between May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient.Results A total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08-9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%).Conclusions Optical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy. Trial registration The study was registered with the UMIN database (ID: 000031712).UMIN000031712. Registered 16 March 2017, https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000031712
Analysis of Exosome-derived MicroRNAs as Early Biomarkers of Lipopolysaccharide-induced Acute Kidney Injury in Rats
Authors: Da-Silva Carolina Carvalho Serres , Anauate Ana Carolina , Maquigussa Edgar , Guirão Tatiana Pinotti , Novaes Antônio da Silva , Boim Mirian A 
Published: September 2020

Abstract
Background: Sepsis contributes to the high prevalence of acute kidney injury (AKI), which mainly occurs in hospitalized patients. The delay in AKI detection is a risk factor for death and chronicity; thus, early diagnosis is essential for initiating proper treatment strategies. Although serum creatinine is used as biomarker, it is increased in plasma serum creatinine only at late stages of AKI. MicroRNAs (miRNAs), a class of noncoding RNAs responsible for gene regulation, can be found in biological fluids within vesicles such as exosomes and may be promising tools for the early detection of AKI. We aimed to identify potential blood miRNAs that can be used as early biomarkers of sepsis-induced AKI in rats. Methods: Adult male Wistar rats received a single dose of lipopolysaccharide (LPS). The earliest significant increase in serum creatinine was detected 4 h after LPS administration. To evaluate whether miRNAs could act as early biomarkers, blood samples were collected before and 2 h after LPS infusion. Serum NGAL levels were used as a comparative marker. Results: Serum miRNAs were derived from exosomes, and their expression were evaluated by the PCR array. miR-181a-5p and miR-23b-3p showed higher expression in LPS-treated rats than in the control animals (p<0.05). Bioinformatics analysis showed that both miRNAs target molecules associated with transcription factors that regulate genes related to proinflammatory cytokines. Conclusion: Considering that LPS activates transcription factors that lead to the production of proinflammatory cytokines, possible premature changes in the serum levels of miR-181a-5p and miR-23b-3p may be used to identify sepsis-induced AKI earlier.
Exploring Views of Orthopaedic Surgeons, Rheumatologists, and General Practitioners About Osteoarthritis Management
Authors: Wallis Jason Andrew , Barton Christian J , Brusco Natasha K , Kemp Joanne L , Sherwood James , Young Kirby , Jennings Sophie , Trivett Adrian , Ackerman Ilana N 
Published: September 2020

Abstract
Background: Delivery of recommended treatments for hip and knee osteoarthritis (OA) is known to be discordant with guideline recommendations. However, professional opinions related to OA management across medical and surgical disciplines are not well understood. The aim of this study was to explore the views of medical professionals about management of hip and knee OA.Methods: Qualitative study. Semi-structured individual interviews were conducted with orthopaedic surgeons, rheumatologists and general practitioners routinely involved in the management of OA. Interviews were audiotaped, transcribed, member-checked, coded and thematically analysed. Results: Fifteen medical professionals were interviewed. Three main themes were: (i) recognition of the importance of non-surgical management of hip and knee OA, focussed on exercise-therapy, weight management and analgesia, (ii) joint replacement being considered the ‘last resort’ for end stage disease not responding to non-surgical management, and (iii) determination of management ‘success’ through patient perceptions was more common than the use of validated instruments. Views on management broadly converged across disciplines, except for the role of joint replacement, considered an adjunct in the overall management of OA by rheumatologists, and as a definitive cure by orthopaedic surgeons.Conclusions: Aligning with current guidelines, medical professionals recognised the importance of non-surgical management focussed on exercise-therapy for hip and knee OA, and concurred that joint replacement surgery should be a last resort. A focus on patient education was less prominent, which along with implementation of validated outcome measures in routine medical practice, may require greater health system support.
Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract.
Authors: Schnell Matthias , Kurup Drishya , Wirblich Christoph 
Published: September 2020

Abstract
Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.
Effect of ultrasound-guided transversus abdominis plane block with rectus sheath block on patients undergoing laparoscopy-assisted radical resection of rectal cancer: a randomized, double-blind, placebo-controlled trial
Authors: Liang Min , Xv Xia , Ren Chunguang , Yao Yongxing , Gao Xiujuan 
Published: September 2020

Abstract
BackgroundMany patients complain of pain following laparoscopic surgery. Clinicians have used ultrasound-guided posterior transversus abdominis plane block (TAPB) and rectus sheath block (RSB) for multimodal analgesia after surgery. We investigated the analgesic effects of US-guided posterior TAPB with RSB on postoperative pain following laparoscopy-assisted radical resection of early-stage rectal cancer.MethodsSeventy-eight adults scheduled for laparoscopy-assisted radical resection of rectal cancer were enrolled in this double-blind placebo-controlled trial. Patients were randomized into 3 groups: the TR Group underwent US-guided bilateral posterior TAPB (40 mL 0.33% ropivacaine) with RSB (20 mL 0.33% ropivacaine); the T Group underwent US-guided bilateral posterior TAPB alone; and the Control Group received saline alone. All patients also had access to patient-controlled intravenous analgesia (PCIA) with sufentanil. The primary outcome was postoperative sufentanil consumption at 0–24, 24–48, and 48–72 h. The secondary outcomes were postoperative pain intensity and functional activity score at rest and while coughing for the same three time periods, intraoperative medication dosage, use of rescue analgesia, recovery parameters, and adverse effects.ResultsThe three groups had no significant differences in baseline demographic and perioperative data, use of intraoperative medications, recovery parameters, and adverse effects. The TR group had significantly lower postoperative use of PCIA and rescue analgesic than in the other two groups (P < 0.05), but the Control Group and T Group had no significant differences in these outcomes.ConclusionsPostoperative US-guided posterior TAPB with RSB reduced postoperative opioid use in patients following laparoscopy-assisted radical resection of rectal cancer.Trial registrationThe trial was registered with chictr.org (ChiCTR2000029326) on January 25, 2020.
Fungus (Alternaria sp.) Mediated Silver Nanoparticles Synthesis, Characterization and Application as Phyto-Pathogens Growth Inhibitor
Authors: Win Theint Theint , Khan Sikandar , Fu Pengcheng 
Published: September 2020

Abstract
Background: Biogenic nanoparticles have proved to be effective biocontrol agents for certain plant diseases. It possesses the potential for extensive use for sustainable agriculture. Many attempts have been made to synthesize nano-based antifungal compounds for the management of soil borne pathogenic fungi for crops.Results: In our work, silver nanoparticles (AgNPs) was constructed with phytopathogenic fungi (Alternaria sp.) which was isolated from banana cultivated soil. Alternaria sp. was able to grow rapidly and produce highly bioactive compounds as safe antifungal agent against plant pathogenic fungi (Fusarium spp. and Alternaria sp.). The size of synthesized silver nanoparticles ranged between 5-10 nm. Analytic tools, such as UV-visible spectroscopy, Fourier transformed infra-red (FTIR) spectroscopy, scanning transmission electron microscopy (STEM), EDS and elemental mapping were used to visualize the formation of AgNPs. The UV-visible spectra showed the peak at 435 nm. The maximum inhibition zone was observed at 100 µl concentration of AgNPs for Fusarium oxysporum (21 ± 2 mm) following Alternaria sp. (20± 2 mm), suggested that the efficacy of the biosynthesized NPs against the phytopathogenic fungi.Conclusions: The resulting AgNPs showed distinct antifungal activity against selected pathogenic plant fungi. The work indicates that green reduction and biogenic synthesis of nanoparticles with benign fungi is an effective, low cost, sustainable and environmentally friendly approach for prevention of soil borne plant diseases.
Assessing the Quality of Deliberative Stakeholder Consultations with Pediatric Palliative Care Clinicians and Oncologists in Canada
Authors: Rahimzadeh Vasiliki , Longo Cristina , Gagnon Justin , Fernandez Conrad , Bartlett Gillian 
Published: September 2020

Abstract
Objective—This paper presents findings from a quality assessment of deliberative stakeholder consultations with healthcare professionals in Canada on the implementation of a precision diagnostic for life-threatening pediatric brain tumors. Background—Advanced understanding of the basic biology and pharmacogenomics of pediatric brain tumors portend a clinical future in which oncologists base their clinical decisions in large part on results from laboratory derived tests (LDT) using next generation sequencing. Less is known, however, about how interprofessional healthcare teams perceive the opportunities and challenges of adopting LDTs in clinical practice, or how to best communicate LDT results to pediatric patients and their families. Deliberative stakeholder consultations present a promising alternative to traditional deliberative democratic methods. They allow researchers to unveil normative ethical and social values underpinning a forthcoming policy or new standard of care from the perspectives of key stakeholder groups, as well as make practical recommendations relevant for implementation.Methods—Using the DeVries framework for assessing the quality of deliberative process and information, we analyzed data from 44 post-consultation evaluation surveys from pediatric oncology and palliative care teams at two tertiary pediatric healthcare centers in Canada. Medians/means based on a 10-point Likert scale are reported. We also conducted turn-taking analysis and word-contribution analysis from the text transcriptions of each deliberation to assess equality of participation.Results—Deliberants agreed the quality of the deliberative process was fair (averages ranging from 9-10/10) and the opportunities to both receive expert information and discuss with others about the implementation of a new LDT were helpful (9.5/10). While the session improved understanding of the implementation barriers and opportunities, the session had marginal effects on deliberants’ perceived impact on their own clinical practice where median ratings ranged from 3-10/10. Participation was proportionate in at least four of the six deliberations, where no deliberant took more than 20% of total turns and contributed equal to, or less than 20% of total words.Conclusion—The quality assessments performed lend evidence to the informational value and overall fairness of the deliberative process achieved in this study to identify implementation and communication needs of healthcare professionals at the point when LDTs become standard for diagnosing life-threatening brain tumors in children.
The I, the T or the Q? Which fishing opportunity attributes are associated with sustainable fishing?
Authors: Oostdijk Maartje , Carpenter Griffin 
Published: September 2020

Abstract
While several prominent studies link the use of individual transferable quotas (ITQs) to sustainable fishing, it remains unclear which attributes of this system (i.e., individual, transferable, or quota), or any other system, lead to sustainable outcomes. To test for a linkage between management systems and sustainable fishing, we systematically classified how fishing opportunities are allocated for 443 fish stocks from 1990 to 2018 to produce the largest database of its kind. Using mixed-effects models and a difference-in-differences approach, we tested the occurrence of system attributes against two metrics of sustainable fishing: mortality (i.e., overfishing) and biomass (i.e., overfished). Our results reveal that quota limits and individual allocation reduce the probability of overfishing, but offer no evidence supporting the transferability of fishing opportunities or the length of time they are held for. These results highlight the importance of considering specific attributes in the design of fisheries management systems.