bluuebunny/crossref_metadata_2025_split huggingface dataset:
An international survey on aminoglycoside practices in critically ill patients: the AMINO III study
Authors:   The Azurea Network, Roger Claire , Louart Benjamin , Elotmani Loubna , Barton Greg , Escobar Leslie , Koulenti Despoina , Lipman Jeffrey , Leone Marc , Muller Laurent , Boutin Caroline , Amour Julien , Banakh Iouri , Cousson Joel , Bourenne Jeremy , Constantin Jean-Michel , Albanese Jacques , Roberts Jason A. , Lefrant Jean-Yves 
Published: March 2021

Abstract
Background
While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock.

Results
We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38–65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1–3) days, the number of doses was 2 (1–2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5–43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes.

Conclusion
Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary.
Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov
Nuclear lamina invaginations are not a pathological feature of C9orf72 ALS/FTD
Authors: Coyne Alyssa N. , Rothstein Jeffrey D. 
Published: March 2021

AbstractThe most common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) is a GGGGCC hexanucleotide repeat expansion (HRE) in the C9orf72 gene. While direct molecular hallmarks of the C9orf72 HRE (repeat RNA foci, dipeptide repeat protein pathology) are well characterized, the mechanisms by which the C9orf72 HRE causes ALS and the related neurodegenerative disease frontotemporal dementia (FTD) remain poorly understood. Recently, alterations to the nuclear pore complex and nucleocytoplasmic transport have been accepted as a prominent pathomechanism underlying C9orf72 ALS/FTD. However, global disruptions to nuclear morphology and the nuclear lamina itself remain controversial. Here, we use a large number of induced pluripotent stem cell derived spinal neurons and postmortem human motor cortex sections to thoroughly examine nuclear morphology and nuclear lamina disruptions with light microscopy. In contrast to previous studies in artificial overexpression model systems, endogenous levels of the C9orf72 HRE do not increase the frequency of nuclear lamina invaginations. In addition, the C9orf72 HRE has no impact on overall nuclear shape and size. Notably, the frequency of nuclear Lamin B1 invaginations increases with cellular aging, independent of the C9orf72 HRE. Together, our data suggest that nuclear morphology is unaltered in C9orf72 ALS/FTD.
Preliminary photographs and improved positives: discovering the New York Public Library’s Arctic Exploration album
Authors: Basso Elena , Pozzi Federica , Keister Jessica , Cronin Elizabeth 
Published: March 2021

Abstract
In the late 19th and early 20th centuries, original photographs were sent to publishers so that they could be reproduced in print. The photographs often needed to be reworked with overpainting and masking, and such modifications were especially necessary for low-contrast photographs to be reproduced as a letterpress halftone. As altered objects, many of these marked-up photographs were simply discarded after use. An album at The New York Public Library, however, contains 157 such photographs, all relating to the Jackson–Harmsworth expedition to Franz Josef Land, from 1894 to 1897. Received as gifts from publishers, the photographs are heavily retouched with overpainting and masking, as well as drawn and collaged elements. The intense level of overpainting on many of the photographs, but not on others, raised questions about their production and alteration. Jackson’s accounts attested to his practice of developing and printing photographs on site, testing different materials and techniques—including platino-bromide and silver-gelatin papers—to overcome the harsh environmental conditions. In this context, sixteen photographs from the album were analyzed through a combination of non-invasive and micro-invasive techniques, including X-ray fluorescence (XRF) spectroscopy, fiber optics reflectance spectroscopy (FORS), Raman and Fourier-transform infrared (FTIR) spectroscopies, and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDS). This analytical campaign aimed to evaluate the possible residual presence of silver halides in any of the preliminary and improved photographs. The detection of these compounds would be one of several factors supporting a hypothesis that some of the photographs in the album were indeed printed on site, in the Arctic, and, as a result, may have been impacted by the extreme environment. Additional goals of the study included the evaluation of the extent of retouching, providing a full characterization of the pigments and dyes used in overpainted prints, and comparing the results with contemporaneous photographic publications that indicate which coloring materials were available at the time. Further analyses shed light on the organic components present in the binders and photographic emulsions. This research has increased our knowledge of photographic processes undertaken in a hostile environment such as the Arctic, and shed light on the technical aspects of photographically illustrating books during the late 19th and early 20th centuries.
Characterization of seventeenth century papers from Valvasor's collection of the Zagreb Archdiocese
Authors: Dragojević Andreja , Gregor-Svetec Diana , Vodopivec Tomažič Jedert , Lozo Branka 
Published: March 2021

Abstract
Valvasor's library is a unique example of a Seventeenth century personal library, including over 7300 prints and 1530 books. Today, it is kept in the Metropolitan Library of the Zagreb Archdiocese which is part of the Croatian State Archives. In this study, we analysed a selection of papers from Valvasor's collection (VC) of unknown origin and composition. We used a dual approach, combining the results of the analyses of two sets of samples to find the most useful tools for the characterization of historical handmade papers. 144 randomly selected papers were included in the study. As the VC is a cultural heritage, only non-destructive analyses were used, such as visual inspection, surface imaging, measurements of thickness and the determination of optical properties (brightness, yellowness, opacity and gloss). According to the optical properties, papers from the VC could be characterized as yellowish and opaque, without gloss. Due to the fact that the VC papers could not be destroyed, we took another set of samples consisting of 10 historical papers (HP) from archival materials, dating from the 16th to nineteenth century, and subjected them to non-destructive, as well as micro-destructive analyses. This was done to supplement the findings of non-destructive analyses of the original collection. Initially, spot tests were performed to determine water absorbency and to identify the presence of lignin and starch in the paper samples. SEM–EDS and XRF were applied for the identification of inorganic elements. FTIR analyses were used to identify the chemical structures of the paper components. Microscopic analyses were performed in two ways: the paper surface was imaged with a digital microscope, and the morphological characteristics of the fibres were studied using an optical microscope. The dominant fibres present were flax and hemp, with a smaller proportion of cotton. Additionally, thick and thin light brown fibres resembling straw were detected. The presence of calcium-containing components, gelatine and alum could be confirmed with SEM–EDS, XFR and FTIR analysis. Comparing the results of analyses performed on two sets of samples a connection was explored by which it was possible to define the characterization of VC papers. The main goal of the study was to document and characterize a specific collection for the future use of researchers of handmade paper or paper conservators. Furthermore, the study may serve as a model approach for other researchers who seek to document the characteristics of paper in their collections.
Price and reimbursement of advanced therapeutic medicinal products in Europe: are assessment and appraisal diverging from expert recommendations?
Authors: Ronco Virginia , Dilecce Myriam , Lanati Elena , Canonico Pier Luigi , Jommi Claudio 
Published: March 2021

Abstract
Background
Advanced therapy medicinal products (ATMPs) represent an important cornerstone for innovation in healthcare. However, uncertainty on the value, the high average cost per patient and their one-shot nature has raised a debate on their assessment and appraisal process for pricing and reimbursement (P&R) purposes. This debate led experts providing for recommendations on this topic. Our primary objective is to investigate the ATMPs P&R process in the main five European countries and to understand if this process is consistent with published P&R expert recommendations. We also investigated the current ATMP pipelines to understand if future ATMPs will create challenges for their P&R process.

Methods
P&R framework for ATMPs in the European Major five (EU5) countries was investigated through a literature search on PubMed, institutional websites of National Health Authorities and grey literature. The ATMPs pipeline database was populated from a clinical trial database (clinicaltrials.gov), relying on inclusion and exclusion criteria retrieved from the literature.

Results
Reimbursement status of ATMPs is different across the EU5 countries, with the exception of CAR-Ts which are reimbursed in all countries. Standard P&R process in place for other medicinal products is extended to ATMPs, with the exception of some cases in Germany. List prices, where available, are high and, tend to be aligned across countries. Outcome-based Managed Entry Agreements (MEAs) have been extensively used for ATMPs. Extra-funds for hospitals managing ATMPs were provided only in Germany and, as additional fund per episode, in France. The accreditation process of hospitals for ATMPs management was in most countries managed by the national authorities. As far as ATMPs pipeline is concerned, ATMPs in development are mostly targeting non-rare diseases.

Conclusions
Expert recommendations for ATMPs P&R were partially applied: the role of outcome-based MEAs has increased and the selection process of the centres authorized to use these treatments has been enhanced; additional funding for ATMPs management to accredited centres has not been completely considered and annuity payment and broader perspective in cost considerations are far from being put in place. These recommendations should be considered for future P&R negotiations to pursue rational resource allocation and deal with budget constraints.
National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research
Authors:   Sepsis Canada’s National Preclinical Sepsis Platform, Mendelson Asher A. , Lansdell Casey , Fox-Robichaud Alison E. , Liaw Patricia , Arora Jaskirat , Cailhier Jean-François , Cepinskas Gediminas , Charbonney Emmanuel , dos Santos Claudia , Dwivedi Dhruva , Ellis Christopher G. , Fergusson Dean , Fiest Kirsten , Gill Sean E. , Hendrick Kathryn , Hunniford Victoria T. , Kowalewska Paulina M. , Krewulak Karla , Lehmann Christian , Macala Kimberly , Marshall John C. , Mawdsley Laura , McDonald Braedon , McDonald Ellen , Medeiros Sarah K. , Muniz Valdirene S. , Osuchowski Marcin , Presseau Justin , Sharma Neha , Sohrabipour Sahar , Sunohara-Neilson Janet , Vázquez-Grande Gloria , Veldhuizen Ruud A. W. , Welsh Donald , Winston Brent W. , Zarychanski Ryan , Zhang Haibo , Zhou Juan , Lalu Manoj M. 
Published: March 2021

AbstractDespite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies—defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis—are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.
Unintended changes in ocular biometric parameters during a 6-month follow-up period after FS-LASIK and SMILE
Authors: Wang Junjie , Lopes Bernardo T. , Li Hechen , Vinciguerra Riccardo , Cao Si , Wu Songan , Zhu Rong , Wang Qinmei , Zheng Xiaobo , Bao Fangjun , Elsheikh Ahmed 
Published: March 2021

AbstractBackgroundCorneal refractive surgery has become reliable for correcting refractive errors, but it can induce unintended ocular changes that alter refractive outcomes. This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).Methods156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study. Central corneal thickness (CCT), mean curvature of the corneal posterior surface (Kpm), internal anterior chamber depth (IACD) and the length from corneal endothelium to retina (ER) were evaluated before and after surgery over a 6-month period.ResultsBoth the FS-LASIK and SMILE groups (closely matched at the pre-surgery stage) experienced flatter Kpm, shallower IACD and decreased ER 1 week post-surgery (P < 0.01), and these changes were larger in FS-LASIK than in SMILE group. During the 1 week to 6 months follow up period, Kpm, IACD and ER remained stable unlike CCT which increased significantly (P < 0.05), more in the FS-LASIK group.ConclusionsDuring the follow up, the posterior corneal surface became flatter and shifted posteriorly, the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage. These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE. The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.
A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report
Authors: Kitada Tomoya , Masui Toshihiko , Kasai Yosuke , Uchida Yuichiro , Ogiso Satoshi , Ito Takashi , Ishii Takamichi , Seo Satoru , Katsuragawa Hiroyuki , Uemoto Shinji 
Published: March 2021

Abstract
Background
Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis.

Case presentation
The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the “hot spot” and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy.

Conclusions
This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.
Blood chemistry of West African dwarf goats fed treated maize cob- and maize husk-based diets with mixture of microorganisms
Authors: Ibhaze Gladys Abiemwense , Ogunjemite Gbenga Enobong , Fajemisin Adebowale Noah 
Published: March 2021

Abstract
Background
Twenty-four West African Dwarf (WAD) goats with average weight of 6.57 ± 0.56 kg were used in investigating the effect of microbial-treated maize cob and husk diets on blood profile. The goats were assigned to six dietary treatments replicated four times in a completely randomized design. Chopped maize cobs and husks were sterilized for 60 min to eliminate any form of contamination and then inoculated with mixture of 15 ml each of Lactobacillus delbrueckii and Neurospora crassa and incubated anaerobically for 5 days and then air-dried. The treated maize cob and husk were incorporated in the diets at the rate of 0% (diet), 20% (diet B), 30% (diet C) [maize cob diets], and 0% (diet D), 20% (diet E), 30% (diet F) [maize husk diets], respectively. The animals were acclimatized for two weeks while the experimental period lasted for 56 days. A completely randomized design was adopted.

Results
The results showed that the dietary treatments significantly (P < 0.05) influenced the erythrocyte sedimentation rate which ranged from 0.50 to 1.00 mm/hr. Significant (P < 0.05) differences were observed in the globulin (28.16 g/dl diet A—59.26 g/dl diet B), aspartate aminotransferase (48.00 u/l diet E—128. 25 u/l diet C) and alanine aminotransferase (8.20 u/l diet A—33.33 u/l diet D). Serum electrolytes values were significantly (P < 0.05) influenced by dietary treatments.

Conclusion
Based on the findings of this study, microbial-treated maize cob and husk diets supported erythropoiesis did not induce any liver damage and the serum electrolytes of the animals were improved. Hence, microbial-treated maize cob and husk can be a suitable alternative feed source at 30% incorporation in a complete diet for WAD goats as adverse implications on the health of the animals was not observed.
A novel Arabidopsis phyllosphere resident Protomyces species and a re-examination of genus Protomyces based on genome sequence data
Authors: Wang Kai , Sipilä Timo , Overmyer Kirk 
Published: March 2021

AbstractProtomyces is an understudied genus of yeast-like fungi currently defined as phytopathogens of only Umbelliferae and Compositae. Species relationships and boundaries remain controversial and molecular data are lacking. Of the 82 named Protomyces, we found few recent studies and six available cultures. We previously isolated Protomyces strains from wild Arabidopsis thaliana, a member of Brassicaceae, a family distant from accepted Protomyces hosts. We previously sequenced the genomes of all available Protomyces species, and P. arabidopsidicola sp. nov. strain C29, from Arabidopsis. Phylogenomics suggests this new species occupied a unique position in the genus. Genomic, morphological, and physiological characteristics distinguished P. arabidopsidicola sp. nov. from other Protomyces. Nuclear gene phylogenetic marker analysis suggests actin1 gene DNA sequences could be used with nuclear ribosomal DNA internal transcribed spacer sequences for rapid identification of Protomyces species. Previous studies demonstrated P. arabidopsidicola sp. nov. could persist on the Arabidopsis phyllosphere and Protomyces sequences were discovered on Arabidopsis at multiple sites in different countries. We conclude that the strain C29 represents a novel Protomyces species and propose the name of P. arabidopsidicola sp. nov. Consequently, we propose that Protomyces is not strictly associated only with the previously recognized host plants.