bluuebunny/crossref_metadata_2025_split huggingface dataset:
An introduction to cryo‐FIB‐SEM cross‐sectioning of frozen, hydrated Life Science samples
Authors: HAYLES M.F. , DE WINTER D.A.M. 
Published: August 2020

SummaryThe introduction of cryo‐techniques to the focused ion‐beam scanning electron microscope (FIB‐SEM) has brought new opportunities to study frozen, hydrated samples from the field of Life Sciences. Cryo‐techniques have long been employed in electron microscopy. Thin electron transparent sections are produced by cryo‐ultramicrotomy for observation in a cryo‐transmission electron microscope (TEM). Cryo‐TEM is presently reaching the imaging of macromolecular structures. In parallel, cryo‐fractured surfaces from bulk materials have been investigated by cryo‐SEM.Both cryo‐TEM and cryo‐SEM have provided a wealth of information, despite being 2D techniques. Cryo‐TEM tomography does provide 3D information, but the thickness of the volume has a maximum of 200–300 nm, which limits the 3D information within the context of specific structures. FIB‐milling enables imaging additional planes by creating cross‐sections (e.g. cross‐sectioning or site‐specific X‐sectioning) perpendicular to the cryo‐fracture surface, thus adding a third imaging dimension to the cryo‐SEM. This paper discusses how to produce suitable cryo‐FIB‐SEM cross‐section results from frozen, hydrated Life Science samples with emphasis on ‘common knowledge’ and reoccurring observations.Lay DescriptionLife Sciences studies life down to the smallest details. Visualising the smallest details requires electron microscopy, which utilises high‐vacuum chambers. One method to maintain the integrity of Life Sciences samples under vacuum conditions is freezing. Frozen samples can remain in a suspended state. As a result, research can be carried out without having to change the chemistry or internal physical structure of the samples.Two types of electron microscopes equipped with cryo‐sample handling facilities are used to investigate samples: The scanning electron microscope (SEM) which investigates surfaces and the transmission electron microscope (TEM) which investigates thin electron transparent sections (called lamellae). A third method of investigation combines a SEM with a focused ion beam (FIB) to form a cryo‐FIB‐SEM, which is the basis of this paper. The electron beam images the cryo‐sample surface while the ion beam mills into the surface to expose the interior of the sample. The latter is called cross‐sectioning and the result provides a way of investigating the 3rd dimension of the sample. This paper looks at the making of cross‐sections in this manner originating from knowledge and experience gained with this technique over many years. This information is meant for newcomers, and experienced researchers in cryo‐microscopy alike.
The neurodevelopmental spectrum of synaptic vesicle cycling disorders
Authors: John Abinayah , Ng‐Cordell Elise , Hanna Nancy , Brkic Diandra , Baker Kate 
Published: August 2020

AbstractIn this review, we describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence synaptic vesicle cycling (SVC disorders). Pathogenic variants in each SVC disorder gene lead to disturbance of at least one SVC subprocess, namely vesicle trafficking (e.g. KIF1A and GDI1), clustering (e.g. TRIO, NRXN1 and SYN1), docking and priming (e.g. STXBP1), fusion (e.g. SYT1 and PRRT2) or re‐uptake (e.g. DNM1, AP1S2 and TBC1D24). We observe that SVC disorders share a common set of neurological symptoms (movement disorders, epilepsies), cognitive impairments (developmental delay, intellectual disabilities, cerebral visual impairment) and mental health difficulties (autism, ADHD, psychiatric symptoms). On the other hand, there is notable phenotypic variation between and within disorders, which may reflect selective disruption to SVC subprocesses, spatiotemporal and cell‐specific gene expression profiles, mutation‐specific effects, or modifying factors. Understanding the common cellular and systems mechanisms underlying neurodevelopmental phenotypes in SVC disorders, and the factors responsible for variation in clinical presentations and outcomes, may translate to personalized clinical management and improved quality of life for patients and families.
image
Clinical outcomes of topical bimatoprost for nonsegmental facial vitiligo: A preliminary study
Authors: Kanokrungsee Silada , Pruettivorawongse Duangrat , Rajatanavin Natta 
Published: August 2020

AbstractBackgroundVitiligo is a common acquired pigmentary disorder. Bimatoprost ophthalmic solution was indicated in the treatment of open‐angle glaucoma and eyebrow hypotrichosis. However, lid hyperpigmentation was reported as a complication.ObjectiveTo study the efficacy and safety of 0.01% bimatoprost solution compared with 0.1% tacrolimus ointment in patients with nonsegmental facial vitiligo.MethodsPatients with more than 2 vitiliginous patches on the face were enrolled. Vitiliginous patches were randomized to receive topical 0.1% tacrolimus ointment or 0.01% bimatoprost ophthalmic solution, applied twice daily for 12 weeks. The vitiligo surface area (VSA, cm2) was calculated, and the percentage of repigmentation was assessed.ResultsTen patients completed the study. At the baseline, the mean VSA was comparable between the two groups. By week 12, the VSA decreased at a statistically significant level among both groups compared to the baseline (P < .05). However, there was not a statistically significant difference between both groups. In terms of repigmentation at week 12, 20% of the patients in the bimatoprost group and 10% in the tacrolimus group achieved >50% repigmentation; the overall grading score between two groups were not different at a statistically significant level. The side effects of bimatoprost were reported as itching and burning. There were no changes in intraocular pressure in 2 patients who had lid involvement.ConclusionTopical bimatoprost solutions were safe and effective for the treatment of nonsegmental facial vitiligo with comparable results to tacrolimus ointment. It can be considered as an alternative treatment for facial vitiligo.
PURPOSE T in Swedish hospital wards and nursing homes: A psychometric evaluation of a new pressure ulcer risk assessment instrument
Authors: Hultin Lisa , Karlsson Ann‐Christin , Öhrvall Margareta , Coleman Susanne , Gunningberg Lena 
Published: August 2020

AbstractAimTo evaluate the psychometric characteristics of the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T); reliability (inter‐rater and test–retest) and validity (convergent validity) in a Swedish context.BackgroundPressure ulcers are considered as an adverse event and are a problem in healthcare worldwide. The first step in pressure ulcer prevention is to identify patients that are at risk. PURPOSE T is a new pressure ulcer risk assessment instrument that was developed in the UK using “golden standard” instrument method.DesignObservational, descriptive and comparative.MethodsA total of 235 patients and 28 registered nurses were recruited (May 2018–November 2018) from six hospital wards at a university hospital and two community nursing homes in Sweden. Blinded (ward/nursing home nurses and expert nurses) PURPOSE T assessments and follow‐up retests were undertaken. Cross‐tabulation and kappa statistics were used to examine the reliability, and phi correlation was used to test the convergent validity. The study followed the STROBE guideline.ResultsThe clinical evaluation showed “very good” (kappa) inter‐rater and test–retest reliability for PURPOSE T assessment decision overall. The agreement of “at risk”/“not at risk” for both inter‐rater and test–retest was also high, at least 95.5%. The convergent validity between PURPOSE T and other traditional assessment instruments was moderate.ConclusionThe evaluation of PURPOSE T demonstrated good psychometric characteristics. Further research is needed to evaluate PURPOSE T’s usability among registered nurses.Relevance to clinical practiceThere is a lack of evidence‐based validated pressure ulcer risk assessment instruments for use in health care. According to our findings, the Swedish version of PURPOSE T could be used in hospitals and nursing homes to identify patients in risk or with pressure ulcers.
The impact of HPV vaccination on the prevalence of oropharyngeal cancer (OPC) in a hospital‐based population: A cross‐sectional study of patient’s registry
Authors: Katz Joseph 
Published: August 2020

AbstractBackgroundHuman papillomavirus (HPV) vaccines have been used for the prevention of cervical cancers, and their clinical efficacy has not been well established in the prevention of oropharyngeal cancer (OPC), in spite of the common viral etiology. Therefore, they are still not routinely prescribed for the prevention of this cancer.MethodsWe have used the i2b2 data repository to analyze the interrelations between the hospital population, OPC, vaccinated patients, and patients that were both vaccinated and developed OPC.ResultsFrom a total hospital population of 1 310 334 patients, 23 174 (1.76%) patients were vaccinated for HPV. One third were males, and two thirds were females. The total number of OPC was 4380 (0.3%) from the total population, of which 3013 (69%) were men. The highest prevalence of OPC was found in the age‐group of 65‐74 (37% of all cases). Four patients (0.017%) of the vaccinated group had developed OPC. Patients who were not vaccinated for HPV had a 19 times increased risk of developing OPC compared with those who were vaccinated (RR 19.3657, 95% CI 7.2655 to 51.6177, P = .0001). The risk was increased in both sexes. The RR in the male group was 23.8 (P = .0015, 95% CI) and in the female group 9.34 (P = .0001, 95% CI 3.0110 to 29.0121). The age distribution in the OPC group was significantly different from the age distribution in the HPV‐vaccinated group (P = .0418) by Mann‐Whitney test. 4376 non‐vaccinated patients have developed OPC.ConclusionsThe present study showed that HPV‐vaccinated group had a reduced prevalence of OPC compared with the non‐vaccinated group.
Acid Effects on the Physical Properties of Different CAD/CAM Ceramic Materials: An in Vitro Analysis
Authors: Al‐Thobity Ahmad M. , Gad Mohammed M. , Farooq Imran , Alshahrani Abdullah S. , Al‐Dulaijan Yousif A. 
Published: August 2020

AbstractPurposeTo evaluate the flexural strength, elastic modulus, microhardness, and surface roughness of monolithic zirconia, lithium disilicate ceramics, and feldspathic ceramics after being exposed to different acidic solutions.Materials and MethodsRectangular specimens (n = 180) were prepared from three different ceramic materials: lithium disilicate, monolithic zirconia, and feldspathic porcelain. Initial Surface roughness of ninety specimens (n = 30/material) was evaluated using an optical noncontact profilometer. Thirty specimens of each material were immersed in one of the following solutions (n = 10/group): citric acid; acidic beverage; and artificial saliva, which served as the control. Post immersion surface roughness, flexural strength, and elastic modulus were determined using an optical noncontact profilometer and three‐point bending test. Another thirty specimens of each material were immersed in the aqueous solutions (n = 10/group) following the same protocol and subjected to microhardness test using a Vickers diamond microhardness tester. A scanning electron microscope (SEM) was used to examine the surface characteristics changes. ANOVA and Post‐hoc Tukey's Kramer tests were used for data analysis (α = 0.05).ResultsImmersion in different solutions did not affect the flexural strength and elastic modulus of lithium disilicate or zirconia. Microhardness and surface roughness were significantly affected in all groups (p < 0.05). For feldspathic porcelain groups, the flexural strength and elastic modulus were significantly decreased in the citric acid group (p = 0.045 and p = 0.019). Also, there were significant differences among all feldspathic porcelain groups (p = 0.001) in terms of microhardness and surface roughness values.ConclusionsThe tested acidic agents significantly affected the flexural strength, elastic modulus, surface roughness, and microhardness of feldspathic porcelain. However, the flexural strength and elastic modulus of evaluated lithium disilicate and zirconia did not change significantly.
Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations
Authors: Ma Xu , Han Sen , Liu Ying , Liu Jing-Tao , Fang Jian , Zhang Yan-Hua 
Published: August 2020

Abstract

Objectives
To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs).

Methods
Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated.

Key findings
In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes.

Conclusions
The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.
The Transformation of the Innovation Process: How Digital Tools are Changing Work, Collaboration, and Organizations in New Product Development*
Authors: Marion Tucker J. , Fixson Sebastian K. 
Published: August 2020

Over the past several decades, digitization has invaded all areas of human activity, including innovation. The result of digitization of existing tools for design and collaboration, and the introduction of entirely new digital tools, is a far more substantive change of innovation than previous generations of tools enabled. It affects not only the quality of the output and speed of its generation, but it affects the innovation work itself, changes work content, collaboration patterns, decision authority, organizational set‐ups, governance structures, firm boundaries, and ultimately entire ecosystems.In this paper, the digitization of New Product Development (NPD), a subset of innovation, is studied to pursue two research questions: (1) How has the digital tool landscape in NPD changed over the past 15 years, and (2) how have these changes affected how firms innovate?This research uses a longitudinal multi‐method, qualitative approach to deep dive into actual use cases of digital design tools such as computer‐aided design CAD and new tools such as collaborative information technology (CIT). The changes in these tools and observations into how these tools are transforming the very nature of how things are designed is the research focus of this study.These tools have become increasingly more sophisticated while being easier to use and are integrated earlier in the design process. As a result, digital tools have a far broader reaching impact than previous generation of tools. Not only do they affect output and process efficiency, but they also increase depth and breadth of the work of individual innovators, they lead to rearrangement of the entire innovation processes, enable new configurations of people, teams, and firms, and rewrite the rules on how knowledge management acts as a critical competitive capability. The progression of digitization is laying the groundwork for changes to what firms are and do and points to different ways of organizing, specializing, and training for NPD professionals.
Taxonomic Shift Over a Phosphorus Gradient Affects the Stoichiometry and Fatty Acid Composition of Stream Periphyton
Authors: Iannino Alessandra , Vosshage Alexander Tim Ludwig , Weitere Markus , Fink Patrick 
Published: August 2020

Phosphorus enrichment of stream ecosystems generally increases primary production in the benthos, but the consequences of eutrophication for the nutritional quality of periphyton for grazers are less clear. On short timescales, high phosphorus inputs may lead to reduced C:P ratios and high essential fatty acid contents of periphyton, which are both considered important determinants of food quality for grazers. However, nutrient enrichment may alter the taxonomic composition of periphyton and favor the growth of less palatable algal taxa. In this study, periphyton was grown under a gradient of dissolved phosphorus availability from 5 to 100 µg P · L−1, to investigate eutrophication effects on periphyton taxonomy, C:N:P stoichiometry, and fatty acid composition. After 1 month, periphyton grown under oligotrophic conditions was mainly composed of diatoms (~86%). With increasing phosphorus availability, diatoms were gradually outcompeted by chlorophytes and cyanobacteria, which were the predominant taxon under eutrophic conditions. Unexpectedly, periphyton C:P ratios increased with greater phosphorus supply, from ~280 under oligotrophic conditions up to ~790 at 100 µg · L−1, reflecting a tendency of chlorophytes and cyanobacteria to produce more biomass per unit of assimilated phosphorus compared to diatoms. Periphyton content of essential polyunsaturated fatty acids relative to biomass followed a unimodal relationship with phosphorus availability and peaked at intermediate phosphorus levels, likely as a result of both taxonomic and nutrient effects. Our results demonstrate that phosphorus‐driven eutrophication of freshwater ecosystems may worsen periphyton nutritional quality due to taxonomic sorting, which may further lead to lower growth and reproduction of herbivores.
Long‐term outcome of Miniature Schnauzers with genetically confirmed demyelinating polyneuropathy: 12 cases
Authors: Farré Mariné Alba , Granger Nicolas , Bertolani Coralie , Mascort Boixeda Joan , Shelton G. Diane , Luján Feliu‐Pascual Alejandro 
Published: August 2020

AbstractBackgroundA demyelinating polyneuropathy with focally folded myelin sheaths was reported in 3 Miniature Schnauzers in France in 2008 and was predicted to represent a naturally occurring canine homologue of Charcot‐Marie‐Tooth (CMT) disease. A genetic variant of MTRM13/SBF2 has been identified as causative in affected Miniature Schnauzers with this polyneuropathy.ObjectiveTo provide data on the long‐term progression in affected Miniature Schnauzers from Spain confirmed with the MTRM13/SBF2 genetic variant.AnimalsTwelve Miniature Schnauzers presented between March 2013 and June 2019.MethodsOnly dogs presented with consistent clinical signs and homozygous for the MTRM13/SBF2 genetic variant were included. Clinical signs, age of onset and presentation, time from onset to presentation, treatment, outcome, and time from diagnosis to final follow‐up were retrospectively reviewed.ResultsThe hallmark clinical signs at the time of presentation were regurgitation with radiologically confirmed megaesophagus (11/12) and aphonic bark (11/12) with or without obvious neuromuscular weakness despite electrodiagnostic evidence of appendicular demyelinating polyneuropathy. Age of onset and clinical presentation were 3‐18 and 4‐96 months, respectively. Treatment was mostly symptomatic and consisted of head elevation during meals, antacids, prokinetics, bethanechol, sildenafil, mirtazapine, or some combination of these. During the follow‐up period (7‐73 months), clinical signs were unchanged in (11/12) cases with aspiration pneumonia developing occasionally (6/12) and being the cause of death in 1 dog.Conclusions and Clinical ImportanceDemyelinating polyneuropathy of Miniature Schnauzers tends to remain stable over the long term leading to a good prognosis with preventive feeding measures and symptomatic treatment to control aspiration pneumonia.
Sublethal mechanical shear stress increases the elastic shear modulus of red blood cells but does not change capillary transit velocity
Authors: McNamee Antony P. , Tansley Geoff D. , Simmonds Michael J. 
Published: August 2020

AbstractBlood exposure to supraphysiological shear stress within mechanical circulatory support is suspected of reducing red blood cell (RBC) deformability and being primal in the pathogenesis of several secondary complications. No prior works have explored RBC dynamics with the resolution required to determine shear elastic modulus, and/or cell capillary velocity, following exposure to mechanical stresses. Healthy RBCs were exposed to 0, 5, 50, and 100 Pa in a Couette shearing system. For comparison, blood was also exposed to heat treatment—a method that predictably increases RBC rigidity. Shear modulus assessment required aspiration of single RBCs through narrow micropipettes at known suction force. Cell transit velocities were measured within microchannels in regions of fully developed flow. Supraphysiological shear stress increased the elastic shear modulus by 39% and 69% following exposure to 50 and 100Pa, respectively. Cell transit velocity, however, did not change following shear, with concurrent decreases in cell volume likely nullifying increased shear modulus‐friction interactions. Differences observed were consistent with our internal control (heat treatment), supporting that cell mechanics are significantly impaired following supraphysiological‐sublethal shear exposure. Given mechanical circulatory support operates at shear stresses consistent with the present study, it is plausible that these devices induce fundamental impairment to the material properties of RBCs.
SMC and the bactofilin/PadC scaffold have distinct yet redundant functions in chromosome segregation and organization in Myxococcus xanthus
Authors: Anand Deepak , Schumacher Dominik , Søgaard‐Andersen Lotte 
Published: August 2020

AbstractIn bacteria, ParABS systems and structural maintenance of chromosome (SMC) condensin‐like complexes are important for chromosome segregation and organization. The rod‐shaped Myxococcus xanthus cells have a unique chromosome arrangement in which a scaffold composed of the BacNOP bactofilins and PadC positions the essential ParB∙parS segregation complexes and the DNA segregation ATPase ParA in the subpolar regions. We identify the Smc and ScpAB subunits of the SMC complex in M. xanthus and demonstrate that SMC is conditionally essential, with Δsmc or ΔscpAB mutants being temperature sensitive. Inactivation of SMC caused defects in chromosome segregation and organization. Lack of the BacNOP/PadC scaffold also caused chromosome segregation defects but this scaffold is not essential for viability. Inactivation of SMC was synthetic lethal with lack of the BacNOP/PadC scaffold. Lack of SMC interfered with formation of the BacNOP/PadC scaffold while lack of this scaffold did not interfere with chromosome association by SMC. Altogether, our data support that three systems function together to enable chromosome segregation in M. xanthus. ParABS constitutes the basic and essential machinery. SMC and the BacNOP/PadC scaffold have different yet redundant roles in chromosome segregation with SMC supporting individualization of daughter chromosomes and BacNOP/PadC making the ParABS system operate more robustly.