bluuebunny/crossref_metadata_2025 huggingface dataset:
Microgravity and Radiation Effects on Astronaut Intervertebral Disc Health
Authors: Smith Karenna , Mercuri Jeremy
Published: April 2021

INTRODUCTION: The effects of spaceflight on the intervertebral disc (IVD) have not been thoroughly studied, despite the knowledge that spaceflight increases the risk of herniation of IVDs in astronauts upon return to Earth. However, as long duration missions become more common,
fully characterizing the mechanisms behind space-induced IVD degeneration becomes increasingly imperative for mission success. This review therefore surveys current literature to outline the results of human, animal, and cell-level studies investigating the effect of microgravity and radiation
exposure on IVD health. Overall, recurring study findings include increases in IVD height in microgravity conditions, upregulation of catabolic proteases leading to a weakening extracellular matrix (ECM), and both nucleus pulposus (NP) swelling and loss of annulus fibrosus (AF) fiber alignment
which are hypothesized to contribute to the increased risk of herniation when reloading is experienced. However, the limitations of current studies are also discussed. For example, human studies do not allow for invasive measures of the underpinning biochemical mechanisms, correlating animal
model results to the human condition may be difficult, and cellular studies lack incorporation of ECM and other complexities that mimic the native IVD microarchitecture and environment. Moving forward, the use of three-dimensional organoid culture models that incorporate IVD-specific human
cells, ECM, and signals as well as the development of cell- and ECM-level computational models may further improve our understanding of the impacts that spaceflight has on astronaut IVD health.Smith K, Mercuri J. Microgravity and radiation effects on astronaut intervertebral disc
health. Aerosp Med Hum Perform. 2021; 92(5):342352.
Penguin Suit and Fetal Position Finite Element Model to Prevent Low Back Pain in Spaceflight
Authors: Zhang Shuai , Wang Kuan , Zhu Rui , Jiang Chenghua , Niu Wenxin
Published: April 2021

BACKGROUND: This study aimed to investigate the biomechanical effects of different interventions on astronauts lumbar intervertebral discs in a microgravity environment during spaceflight and in a gravity environment when the astronaut returns.METHODS: A finite element
model of the L4L5 lumbar segment was developed with eight loading schemes representing different interventions. The loading schemes included no intervention, wearing a penguin suit, sleeping in a fetal position, wearing a penguin suit combined with sleeping in the fetal position, reclining
for 4 or 16 h/d, and maintaining upright posture for 4 or 16 h/d.RESULTS: Without intervention, the microgravity environment led to increased central pore pressure, radial displacement, and water content in the lumbar intervertebral disc. Wearing a penguin suit combined with sleeping
in the fetal position can reduce disc pore pressure, axial stress, radial displacement, and water content to 0.156 MPa, 11.50 kPa, 0.538 mm, and 1.390%, respectively. When astronauts return to the gravity environment, staying upright for 4 h can reduce the pore pressure, axial stress, radial
displacement, and water content of the intervertebral disc to 0.222 MPa, 10.72 kPa, 0.373 mm, and 0.219%, respectively.CONCLUSION: This study showed that wearing a penguin suit and sleeping in the fetal position both have the potential to protect the lumbar intervertebral disc from
the negative effects caused by microgravity. Remaining in the upright posture for 4 h per day may help squeeze out the water in the intervertebral disc safely when astronauts return to the gravity environment.Zhang S, Wang K, Zhu R, Jiang C, Niu W. Penguin suit and fetal position
finite element model to prevent low back pain in spaceflight. Aerosp Med Hum Perform. 2021; 92(5):312318.
Investigating the impact of Zero Tillage on small farmer’s wheat production and Income: A case of District Sialkot, Pakistan
Authors: Akhtar Muhammad Wasim , Rasool Faisal
Published: April 2021

Zero tillage (ZT) implies the practice of planting a new crop in the soil left unprepared after the harvesting of the previous crop. The most dominant benefit of no-tillage is an improvement in soil biological fertility, making soils more resilient. Zero-tillage also reduces the cost of production and saves time for sowing of wheat by 10-15 days as compared to conventional tillage. District Sialkot was selected as the study areas of this study based on its diversity in agriculture and the probability of zero tillage practices in this area. Two groups of respondents were selected with almost similar socioeconomics characteristics practicing their farming operations under similar biophysical conditions. The first group comprises small farmers who were practicing conventional tillage technology and the second group include small farmers who were practicing zero tillage technology. Against this backdrop, the purpose of this paper is to assess the impact of zero tillage on small farmers’ wheat production and to assess the impact of zero tillage on small farmers’ income arising from the wheat crop. We collected primary data from 150 farmers through a structured questionnaire in district Sialkot of Punjab Province of Pakistan. The study identified that zero tillage wheat growing farmers used more quantity of seed than conventional wheat growing farmers in the study area. While a number of irrigations is also used more in conventional wheat as compared to Zero Tillage wheat. The results reflected that conventional farmers spend more on fertilizer, irrigation, chemical application than the zero tillage farmers. Variable cost is also higher for the conventional technique (Rs. 13698.02) than the zero tillage technique (Rs. 9723.9). Conventional wheat farmers have to spend more not only for irrigation but have to take extra care to look after in form of labor for their wheat crop, because of heavy investment made in conventional tillage wheat crop.
"THE VALUE OF STUMPAGE" WITHIN THE CONTEXT OF ENSURING ECONOMIC SECURITY AND COMPETITIVENESS OF FOREST INDUSTRY
Authors:   Academy of Management of Internal Affairs of Russia, Moscow, Russian Federation, BULGAKOVA MARINA
Published: April 2021

The article contains an analysis of theoretical and practical approaches to assessing the value of the forest on the vine, as limited, but renewable resource that allows you to extract a significant income and meet the diverse needs of society. The use of a critical analysis in the research process allowed the author to present a comparative characteristic of the methods of forming the cost of forest resources intended for harvesting with a detailed description of the calculation methods; and also to establish possible reasons for the emergence of a conflict of interest between the state, as the owner of forest plots, and tenants. V. Pareto' s appeal to the optimum made it possible to reveal the regularity of the effect of «deferred damage» in the Russian forest industry, that is, the impossibility of future generations to meet their own needs for wood products. The approximate calculation of income from logging 1000 m3 of wood, confirming the existence of an economic resource for the formation of the process of competitiveness of the forest industry. The definition of the forest on the root. The author present the genesis of calculating the cost of standing timber, as the most important aspect of the forest economy, which is the starting point for determining the cost of products for end users. The factors that have a negative impact on the state of economic security of the forestry industry have been identified. In the conclusion, it is proposed to transform the mechanism for forming the cost of standing timber, taking into account various indicators, including market value, consumer demand, transport accessibility and quality of wood, which, according to the author, will allow not only comprehensive mechanization of the industry, also contribute to increasing productivity equipment and the development of the competitiveness of the industry.
YOĞUN BAKIM HEMŞİRELERİNİN AĞRILI HASTADA AĞRIYLA BAŞ ETMEDE KULLANDIKLARI YÖNTEMLER VE AĞRIYA YÖNELİK BİLGİ VE DAVRANIŞLARI
Authors: KARGIN Maral , AYTOP Sinem , KURAN İbrahim , ORAL Elif , DOĞAN Fatma
Published: April 2021

Bu araştırma, ağrı ile en sık karşılaşan yoğun bakım hemşirelerinin ağrı ile ilgili kullandıkları yöntemleri ve ağrıya yönelik bilgi ve davranışlarını belirlemek amacı ile yapılmıştır. Tanımlayıcı tipte planlanan araştırmaya bir üniversite hastanesinin yoğun bakım kliniklerinde çalışan 127 hemşire dahil edilmiştir. Verilerin toplanmasında Kişisel Bilgi Formu ile Hemşirelerin Ağrıyla İlgili Bilgi ve Davranış Anketi kullanılmıştır. Yaş ortalaması 28.24±4.81 olan hemşirelerin %68.5’inin kadın, yarısının evli ve %74.8’inin ise lisans eğitim düzeyine sahip olduğu saptanmıştır. Hemşirelerin yarısından fazlasının (%58.3) ağrılı hastanın bakımı ile ilgili eğitim almış olduğu, %46.5’nin sıklıkla ve %32.3’ünün de her zaman ağrılı hasta ile karşılaştığı saptanmıştır. Çalışmada hemşirelerin ağrılı hastaya yönelik uyguladıkları girişim olarak %96.1’inin farmakolojik tedavi kullandıkları belirlenmiştir. Hemşirelerin %45.7’si farmakolojik tedaviyi, ağrıyı geçirmede etkili bir yöntem olduğundan ve %44.9’u ise doktor isteminde bulunmasından dolayı tercih ettiklerini ifade etmişlerdir. Hemşirelerin ağrı ile ilgili bilgi ve davranışlarının toplam puanına bakıldığında [Ort±SS 14.51±2.19], hemşirelerin; %55.1’nin orta, %27.6’sının düşük ve %17.3’ünün de yüksek puana sahip olduğu saptanmıştır. Araştırma bulgularına bakıldığında hemşirelerin büyük çoğunluğunun farmakolojik yöntemleri tercih ettiği, bilgi ve davranış düzeylerinin orta düzeyde olduğu saptanmıştır.
Samtala med omtanke: En blogg om kommunikativa utmaningar för personer med ålderssjukdom
Authors: Malmqvist Ebba , Rosén Emilia
Published: April 2021

Kommunikation är en viktig del i våra liv. Men långt ifrån alla har möjligheten att kommunicera som de vill och önskar. Ålderssjukdomar som demens och Parkinsons påverkar vår möjlighet att kommunicera. Bristande kunskaper kring sjukdomar och dess påverkan ger sämre förutsättningar för de som drabbas. Vi vill lyfta frågan om kommunikationssvårigheter för personer med just ålderssjukdomar - för att du, precis som vi, ska se hur viktigt det är att samtala med omtanke. Om oss Vi som driver den här bloggen är två sistaårsstudenter på kandidatprogrammet Språk, litteratur och medier vid Linköpings Universitet. Vi har i vår utbildning valt att rikta in oss på det svenska språket och intresserar oss särskilt för just språkliga svårigheter. Den här bloggen är en del i ett projekt där vi har i uppgift att på ett kreativt sätt driva en specifik samhällsfråga. / Ebba Malmqvist och Emilia Rosén
Effect of Thoracic Connective Lesion on Inter-Leg Coordination in Freely Walking Stick Insects
Authors: Niemeier Miriam , Jeschke Manon , Dürr Volker
Published: April 2021

Multi-legged locomotion requires appropriate coordination of all legs with coincident ground contact. Whereas behaviourally derived coordination rules can adequately describe many aspects of inter-leg coordination, the neural mechanisms underlying these rules are still not entirely clear. The fact that inter-leg coordination is strongly affected by cut thoracic connectives in tethered walking insects, shows that neural information exchange among legs is important. As yet, recent studies have shown that load transfer among legs can contribute to inter-leg coordination through mechanical coupling alone, i.e., without neural information exchange among legs. Since naturalistic load transfer among legs works only in freely walking animals but not in tethered animals, we tested the hypothesis that connective lesions have less strong effects if mechanical coupling through load transfer among legs is possible. To do so, we recorded protraction/retraction angles of all legs in unrestrained walking stick insects that either had one thoracic connective cut or had undergone a corresponding sham operation. In lesioned animals, either a pro-to-mesothorax or a meso-to-metathorax connective was cut. Overall, our results on temporal coordination were similar to published reports on tethered walking animals, in that the phase relationship of the legs immediately adjacent to the lesion was much less precise, although the effect on mean phase was relatively weak or absent. Lesioned animals could walk at the same speed as the control group, though with a significant sideward bias toward the intact side. Detailed comparison of lesion effects in free-walking and supported animals reveal that the strongest differences concern the spatial coordination among legs. In free walking, lesioned animals, touch-down and lift-off positions shifted significantly in almost all legs, including legs of the intact body side. We conclude that insects with disrupted neural information transfer through one connective adjust to this disruption differently if they experience naturalistic load distribution. While mechanical load transfer cannot compensate for lesion-induced effects on temporal inter-leg coordination, several compensatory changes in spatial coordination occur only if animals carry their own weight.
Sodium Valproate-Induced Chromatin Remodeling
Authors: Mello Maria Luiza S.
Published: April 2021

Valproic acid/sodium valproate (VPA), a drug originally prescribed as an anticonvulsant, has been widely reported to act on epigenetic marks by inducing histone acetylation, affecting the DNA and histone methylation status, and altering the expression of transcription factors, thus leading to modulation of gene expression. All these epigenetic changes have been associated with chromatin remodeling effects. The present minireview briefly reports the main effects of VPA on chromatin and image analysis and Fourier transform infrared (FTIR) microspectroscopy in association with molecular biology methodological approaches to investigate the VPA-induced changes in chromatin structure and at the higher-order supraorganizational level.
Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies
Authors: Parodi Chiara , Di Fede Elisabetta , Peron Angela , Viganò Ilaria , Grazioli Paolo , Castiglioni Silvia , Finnell Richard H. , Gervasini Cristina , Vignoli Aglaia , Massa Valentina
Published: April 2021

Prenatal exposure to valproate (VPA), an antiepileptic drug, has been associated with fetal valproate spectrum disorders (FVSD), a clinical condition including congenital malformations, developmental delay, intellectual disability as well as autism spectrum disorder, together with a distinctive facial appearance. VPA is a known inhibitor of histone deacetylase which regulates the chromatin state. Interestingly, perturbations of this epigenetic balance are associated with chromatinopathies, a heterogeneous group of Mendelian disorders arising from mutations in components of the epigenetic machinery. Patients affected from these disorders display a plethora of clinical signs, mainly neurological deficits and intellectual disability, together with distinctive craniofacial dysmorphisms. Remarkably, critically examining the phenotype of FVSD and chromatinopathies, they shared several overlapping features that can be observed despite the different etiologies of these disorders, suggesting the possible existence of a common perturbed mechanism(s) during embryonic development.
Modulation of Rumen Microbes Through Extracellular Vesicle Released by the Rumen Fluke Calicophoron daubneyi
Authors: Allen Nathan R. , Taylor-Mew Aspen R. , Wilkinson Toby J. , Huws Sharon , Phillips Helen , Morphew Russell M. , Brophy Peter M.
Published: April 2021

Parasite derived extracellular vesicles (EVs) have been proposed to play key roles in the establishment and maintenance of infection. Calicophoron daubneyi is a newly emerging parasite of livestock with many aspects of its underpinning biology yet to be resolved. This research is the first in-depth investigation of EVs released by adult C. daubneyi. EVs were successfully isolated using both differential centrifugation and size exclusion chromatography (SEC), and morphologically characterized though transmission electron microscopy (TEM). EV protein components were characterized using a GeLC approach allowing the elucidation of comprehensive proteomic profiles for both their soluble protein cargo and surface membrane bound proteins yielding a total of 378 soluble proteins identified. Notably, EVs contained Sigma-class GST and cathepsin L and B proteases, which have previously been described in immune modulation and successful establishment of parasitic flatworm infections. SEC purified C. daubneyi EVs were observed to modulate rumen bacterial populations by likely increasing microbial species diversity via antimicrobial activity. This data indicates EVs released from adult C. daubneyi have a role in establishment within the rumen through the regulation of microbial populations offering new routes to control rumen fluke infection and to develop molecular strategies to improve rumen efficiency.
Neurocognitive Predictors of Response to Intervention With GraphoGame Rime
Authors: Wilson Angela , Ahmed Henna , Mead Natasha , Noble Hannah , Richardson Ulla , Wolpert Mary A. , Goswami Usha
Published: April 2021

This study explores the neurocognitive predictors of response to intervention with GraphoGame Rime (GG Rime), an adaptive software game designed to aid the learning of English phonics. A cohort of 398 children (aged 6–7 years) who had participated in a recent randomised controlled trial (RCT) of GG Rime in the United Kingdom were studied. Half were randomly assigned to play GG Rime and the other half were assigned to Business As Usual (BAU). A series of pretests were given prior to the intervention to all participants, designed to measure phonological awareness skills, executive function (EF) skills and the ability to synchronise finger tapping to a rhythmic beat. Rhythmic synchronisation has been linked to reading readiness and early reading attainment, and is related to phonological awareness. Individual differences prior to the intervention in all three types of measure were significantly associated with progression through the game. Gender was also important for progression through the game, with boys progressing significantly further than girls. Vocabulary was not a predictor of progression through the game. Playing time, rhythmic synchronisation, phonological skills and EF skills did not differ by gender. Once playing time and non-verbal cognitive ability were controlled, phonological awareness, EF, rhythmic synchronisation and gender all remained significant predictors of progression through the game. In further analyses comparing these predictors, their interactions and controlling for the autoregressor of prior responsiveness to phonics instruction, phoneme awareness and EF skills were the strongest unique predictors. Analyses with the whole cohort (analysing BAU and GG children independently) showed that all neurocognitive measures contributed to progress in reading and spelling over the school year. We conclude that individual differences in phonological skills and EF skills predict which children will benefit most from computer assisted reading interventions like GG Rime. Further, boys respond better to this computerised intervention than girls. Accordingly, to be maximally beneficial to poor readers, the supplementary use of GG Rime in addition to ongoing classroom literacy instruction could be especially targeted to boys, but should be accompanied by a focus on developing both oral phonological awareness and EF skills.
Case Report: A Novel IL2RG Frame-Restoring Rescue Mutation Mimics Early T Cell Engraftment Following Haploidentical Hematopoietic Stem Cell Transplantation in a Patient With X-SCID
Authors: Steininger Jolanda , Leiss-Piller Alexander , Geier Christoph B. , Rossmanith Raphael , Elfeky Reem , Bra David , Pichler Herbert , Lawitschka Anita , Zubarovskaya Natascha , Artacker Gottfried , Matthes-Leodolter Susanne , Eibl Martha M. , Wolf Hermann M.
Published: April 2021

Mutations of the interleukin 2 receptor γ chain (IL2RG) result in the most common form of severe combined immunodeficiency (SCID), which is characterized by severe and persistent infections starting in early life with an absence of T cells and natural killer cells, normal or elevated B cell counts and hypogammaglobulinemia. SCID is commonly fatal within the first year of life, unless the immune system is reconstituted by hematopoietic stem cell transplantation (HSCT) or gene therapy. We herein describe a male infant with X-linked severe combined immunodeficiency (X-SCID) diagnosed at 5 months of age. Genetic testing revealed a novel C to G missense mutation in exon 1 resulting in a 3’ splice site disruption with premature stop codon and aberrant IL2 receptor signaling. Following the diagnosis of X-SCID, the patient subsequently underwent a TCRαβ/CD19-depleted haploidentical HSCT. Post transplantation the patient presented with early CD8+ T cell recovery with the majority of T cells (>99%) being non-donor T cells. Genetic analysis of CD4+ and CD8+ T cells revealed a spontaneous 14 nucleotide insertion at the mutation site resulting in a novel splice site and restoring the reading frame although defective IL2RG function was still demonstrated. In conclusion, our findings describe a spontaneous second-site mutation in IL2RG as a novel cause of somatic mosaicism and early T cell recovery following haploidentical HSCT.
Blooms of Alexandrium catenella in Coastal Waters of Chilean Patagonia: Is Subantarctic Surface Water Involved?
Authors: Crawford David W. , Montero Paulina , Daneri Giovanni
Published: April 2021

At the southern tip of South America, evidence of shellfish toxicity has been recorded in the accounts of early explorers and shipwreck survivors since the late 16th Century. Blooms of the toxic dinoflagellate Alexandrium catenella were described in the western Magellan Strait in the early 1970s and have since shown a northward progression through Chilean Patagonia, culminating in a catastrophic toxic event around Chiloé Island in 2016. This shift has taken place through coastal areas of extremely sparse human population density, and anthropogenically driven eutrophication is therefore unlikely to be significantly involved, at least in the south. However, human activities – such as salmon cultivation – may play a role in the intensification of blooms in the more densely populated areas of northern Patagonia. In the fjords and channels of Chilean Patagonia, phytoplankton assemblages are shaped by complex interactions between freshwater (FW) run-off and intrusions of subantarctic surface water (SASW). In the context of blooms of A. catenella, we review the properties of SASW – transformed in coastal waters into modified subantarctic water (MSAW). FW input is characterized by very low concentrations of dissolved inorganic nitrogen (DIN) and phosphorus (DIP), but relatively high concentrations of silicic acid (DSi); DIN and DIP are instead supplied predominantly by SASW which is severely deficient in DSi. These waters therefore show strong vertical gradients in DIN, DIP and DSi, but also potentially in dissolved trace metals and CO2. Large scale shifts in the relative inputs of SASW or FW can modify these vertical gradients, potentially forcing competitive changes in phytoplankton assemblages with latitude, with implications for growth and toxicity of A. catenella and other harmful species. The northward shift of blooms of A. catenella could be associated with anomalies in the Southern Annular Mode (SAM) that modify the influence of MSAW through variations in FW input to coastal waters. The historical presence of blooms in southern Patagonia and Tierra del Fuego, combined with the strongly contrasting conditions with latitude and depth, mean that southern Chile represents an ideal natural laboratory to study climatic and oceanographic influences on dynamics of A. catenella populations.
Benthic and Fish Interactions With Pipeline Protective Structures in the North Sea
Authors: Redford Michael , Rouse Sally , Hayes Peter , Wilding Thomas A.
Published: April 2021

An increasing number of pipelines and associated protective materials in the North Sea are reaching the end of their operational life and require decommissioning. Identifying the optimal decommissioning option from an environmental perspective requires an understanding of ecological interactions; currently there is little knowledge as to species associations with pipelines and associated protective materials. This study utilises industry ROV footage from the North Sea to quantify these interactions. A total of 58 taxa were identified, including 41 benthic taxa and 17 fish taxa. Taxa were grouped into seven groups for analysis including four groups for benthic epifauna: grazers, suspension/filter feeders, decapods, and colonial/encrusting taxa. Fish were organised into three groups: pollock, other fish, and other gadoids. Using zero-inflated generalised linear mixed models, we show that abundances of benthic epifauna and fish vary between types of protective structure (e.g., concrete mattresses, rock dump), depth, levels of fishing effort and proximity to oil and gas platforms. Six taxa groups exhibited higher abundances on concrete mattresses than bare pipelines with benthic epifaunal decapods showing the highest difference at 3.04 (1.83, 4.84, 95% CrI) times higher on mattresses compared to bare pipelines. Six groups were higher in abundance within the 500 m fisheries exclusion zone around platforms, compared to outside of the zone, with other gadoids showing the highest difference at 1.83 times (1.09, 2.89, 95% CrI) times higher inside zones. Five groups decreased in abundance with an increase in fishing effort, with the biggest effect observed on grazers which decreased in abundance by 28% (14 – 40, 95% CrI) per 50 h of fishing. We show that pipelines and protective materials are operating as artificial reefs, and our results suggest that removal of infrastructure could result in the loss of habitat and species.
No Impact of Fluconazole to Echinocandins Replacement as First-Line Therapy on the Epidemiology of Yeast Fungemia (Hospital-Driven Active Surveillance, 2004–2017, Paris, France)
Authors: Bretagne Stéphane , Desnos-Ollivier Marie , Sitbon Karine , Lortholary Olivier , Che Didier , Dromer Françoise ,   Participants of the YEASTS
Published: April 2021

Replacement of fluconazole by echinocandins as the first-line therapy for yeast-related fungemia could have an impact on both the mortality rate and the epidemiology of yeast species responsible for candidemia. We analyzed the individual clinical and microbiological data collected through the active surveillance program on yeast fungemia (YEASTS program, 2004–2016, Paris area, France) within 14 University Hospitals. The cohort included 3,092 patients [male:female ratio: 1.56; median age 61.0 years (IQR: 23.8)]. The mean mortality rate within 30 days was 38.5% (1,103/2,868) and significantly higher in intensive care units (690/1,358, 50.8%) than outside (413/1,510, 27.4%, p < 0.0001) without significant change over time. The yeast species distribution [Candida albicans (n = 1,614, 48.0%), Candida glabrata (n = 607, 18.1%), Candida parapsilosis (n = 390, 11.6%), Candida tropicalis (n = 299, 8.9%), Candida krusei (n = 96, 2.9%), rare species (n = 357, 10.6%)], minimal inhibitory concentration distribution, and the distribution between the patient populations (hematological malignancies, solid tumors, without malignancy) did not change either while the proportion of patients ≥60-years increased from 48.7% (91/187) in 2004 to 56.8% (133/234) in 2017 (p = 0.0002). Fluconazole as first-line therapy dramatically decreased (64.4% in 2004 to 27.7% in 2017, p < 0.0001) with a corresponding increase in echinocandins (11.6% in 2004 to 57.8% in 2017, p < 0.0001). Survival rates did not differ according to the first antifungal therapy. The progressive replacement of fluconazole by echinocandins as the first-line antifungal therapy was not associated with change in global mortality, regardless of species involved and antifungal susceptibility profiles. Other factors remain to be uncovered to improve the prognosis of yeast fungemia.
Do Digital Handover Checklists Influence the Clinical Outcome Parameters of Intensive Care Unit Patients? A Randomized Controlled Pilot Study
Authors: Verholen Nina , Vogt Lina , Klasen Martin , Schmidt Michelle , Beckers Stefan , Marx Gernot , Sopka Saša
Published: April 2021

Background: Clinical handovers have been identified as high-risk situations for medical treatment errors. It has been shown that handover checklists lead to a reduced rate of medical errors and mortality. However, the influence of handover checklists on essential patient outcomes such as prevalence of sepsis, mortality, and length of hospitalization has not yet been investigated in a randomized controlled trial (RCT).

Objectives: The aim of the present pilot study was to estimate the effect of two different handover checklists on the 48 h sepsis-related organ failure assessment (SOFA) score and the feasibility of a respective clinical RCT.

Methods: Outcome parameters and feasibility were investigated implementing and comparing an intervention with a control checklist.

Design: Single center two-armed cluster randomized prospective crossover pilot study.

Setting: The study took place over three 1-month periods in an intensive care unit (ICU) setting at the University Hospital Aachen.

Patients/Participants: Data from 1,882 patients on seven ICU wards were assessed, of which 1,038 were included in the analysis.

Intervention: A digital standardized handover checklist (ISBAR3) was compared to a control checklist (VICUR).

Main Outcome Measures: Primary outcome was the 2nd 24 h time window sepsis-related organ failure assessment (SOFA) score. Secondary outcomes were SOFA scores on the 3rd and 5th 24 h time window, mortality, reuptake, and length of stay; handover duration, degree of satisfaction, and compliance as feasibility-related outcomes.

Results: Different sepsis scores were observed only for the 1st 24 h time window after admission to the ICU, with higher values for ISBAR3. With respect to the patient-centered outcomes, both checklists achieved similar results. Average handover duration was shorter for VICUR, whereas satisfaction and compliance were higher for ISBAR3. However, overall compliance was low (25.4% for ISBAR3 and 15.8% for VICUR).

Conclusions: Based on the results, a stratified randomization procedure is recommended for following RCTs, in which medical treatment errors should also be investigated as an additional variable. The use of control checklists is discouraged due to lower acceptance and compliance among healthcare practitioners. Measures should be undertaken to increase compliance with the use of checklists. Clinical outcome parameters should be carefully selected.

Trial Registration:ClinicalTrials.gov, Identifier [NCT03117088]. Registered April 14, 2017.
Evaluation of the Microba Community Profiler for Taxonomic Profiling of Metagenomic Datasets From the Human Gut Microbiome
Authors: Parks Donovan H. , Rigato Fabio , Vera-Wolf Patricia , Krause Lutz , Hugenholtz Philip , Tyson Gene W. , Wood David L. A.
Published: April 2021

A fundamental goal of microbial ecology is to accurately determine the species composition in a given microbial ecosystem. In the context of the human microbiome, this is important for establishing links between microbial species and disease states. Here we benchmark the Microba Community Profiler (MCP) against other metagenomic classifiers using 140 moderate to complexin silicomicrobial communities and a standardized reference genome database. MCP generated accurate relative abundance estimates and made substantially fewer false positive predictions than other classifiers while retaining a high recall rate. We further demonstrated that the accuracy of species classification was substantially increased using the Microba Genome Database, which is more comprehensive than reference datasets used by other classifiers and illustrates the importance of including genomes of uncultured taxa in reference databases. Consequently, MCP classifies appreciably more reads than other classifiers when using their recommended reference databases. These results establish MCP as best-in-class with the ability to produce comprehensive and accurate species profiles of human gastrointestinal samples.
Expanding Diversity of Firmicutes Single-Strand Annealing Proteins: A Putative Role of Bacteriophage-Host Arms Race
Authors: Steczkiewicz Kamil , Prestel Eric , Bidnenko Elena , Szczepankowska Agnieszka K.
Published: April 2021

Bacteriophage-encoded single strand annealing proteins (SSAPs) are recombinases which can substitute the classical, bacterial RecA and manage the DNA metabolism at different steps of phage propagation. SSAPs have been shown to efficiently promote recombination between short and rather divergent DNA sequences and were exploited for in vivo genetic engineering mainly in Gram-negative bacteria. In opposition to the conserved and almost universal bacterial RecA protein, SSAPs display great sequence diversity. The importance for SSAPs in phage biology and phage-bacteria evolution is underlined by their role as key players in events of horizontal gene transfer (HGT). All of the above provoke a constant interest for the identification and study of new phage recombinase proteins in vivo, in vitro as well as in silico. Despite this, a huge body of putative ssap genes escapes conventional classification, as they are not properly annotated. In this work, we performed a wide-scale identification, classification and analysis of SSAPs encoded by the Firmicutes bacteria and their phages. By using sequence similarity network and gene context analyses, we created a new high quality dataset of phage-related SSAPs, substantially increasing the number of annotated SSAPs. We classified the identified SSAPs into seven distinct families, namely RecA, Gp2.5, RecT/Redβ, Erf, Rad52/22, Sak3, and Sak4, organized into three superfamilies. Analysis of the relationships between the revealed protein clusters led us to recognize Sak3-like proteins as a new distinct SSAP family. Our analysis showed an irregular phylogenetic distribution of ssap genes among different bacterial phyla and specific phages, which can be explained by the high rates of ssap HGT. We propose that the evolution of phage recombinases could be tightly linked to the dissemination of bacterial phage-resistance mechanisms (e.g., abortive infection and CRISPR/Cas systems) targeting ssap genes and be a part of the constant phage-bacteria arms race.
A Novel Jumbo Phage PhiMa05 Inhibits Harmful Microcystis sp.
Authors: Naknaen Ampapan , Suttinun Oramas , Surachat Komwit , Khan Eakalak , Pomwised Rattanaruji
Published: April 2021

Microcystis poses a concern because of its potential contribution to eutrophication and production of microcystins (MCs). Phage treatment has been proposed as a novel biocontrol method for Microcystis. Here, we isolated a lytic cyanophage named PhiMa05 with high efficiency against MCs-producing Microcystis strains. Its burst size was large, with approximately 127 phage particles/infected cell, a short latent period (1 day), and high stability to broad salinity, pH and temperature ranges. The PhiMa05 structure was composed of an icosahedral capsid (100 nm) and tail (120 nm), suggesting that the PhiMa05 belongs to the Myoviridae family. PhiMa05 inhibited both planktonic and aggregated forms of Microcystis in a concentration-dependent manner. The lysis of Microcystis resulted in a significant reduction of total MCs compared to the uninfected cells. A genome analysis revealed that PhiMa05 is a double-stranded DNA virus with a 273,876 bp genome, considered a jumbo phage. Out of 254 predicted open reading frames (ORFs), only 54 ORFs were assigned as putative functional proteins. These putative proteins are associated with DNA metabolisms, structural proteins, host lysis and auxiliary metabolic genes (AMGs), while no lysogenic, toxin and antibiotic resistance genes were observed in the genome. The AMGs harbored in the phage genome are known to be involved in energy metabolism [photosynthesis and tricarboxylic acid cycle (TCA)] and nucleotide biosynthesis genes. Their functions suggested boosting and redirecting host metabolism during viral infection. Comparative genome analysis with other phages in the database indicated that PhiMa05 is unique. Our study highlights the characteristics and genome analysis of a novel jumbo phage, PhiMa05. PhiMa05 is a potential phage for controlling Microcystis bloom and minimizing MC occurrence.
Lost in Translation: Simple Steps in Experimental Design of Neurorehabilitation-Based Research Interventions to Promote Motor Recovery Post-Stroke
Authors: Sánchez Natalia , Winstein Carolee J.
Published: April 2021

Stroke continues to be a leading cause of disability. Basic neurorehabilitation research is necessary to inform the neuropathophysiology of impaired motor control, and to develop targeted interventions with potential to remediate disability post-stroke. Despite knowledge gained from basic research studies, the effectiveness of research-based interventions for reducing motor impairment has been no greater than standard of practice interventions. In this perspective, we offer suggestions for overcoming translational barriers integral to experimental design, to augment traditional protocols, and re-route the rehabilitation trajectory toward recovery and away from compensation. First, we suggest that researchers consider modifying task practice schedules to focus on key aspects of movement quality, while minimizing the appearance of compensatory behaviors. Second, we suggest that researchers supplement primary outcome measures with secondary measures that capture emerging maladaptive compensations at other segments or joints. Third, we offer suggestions about how to maximize participant engagement, self-direction, and motivation, by embedding the task into a meaningful context, a strategy more likely to enable goal-action coupling, associated with improved neuro-motor control and learning. Finally, we remind the reader that motor impairment post-stroke is a multidimensional problem that involves central and peripheral sensorimotor systems, likely influenced by chronicity of stroke. Thus, stroke chronicity should be given special consideration for both participant recruitment and subsequent data analyses. We hope that future research endeavors will consider these suggestions in the design of the next generation of intervention studies in neurorehabilitation, to improve translation of research advances to improved participation and quality of life for stroke survivors.
Ventral Striatal Activation During Reward Anticipation of Different Reward Probabilities in Adolescents and Adults
Authors: Bretzke Maria , Wahl Hannes , Plichta Michael M. , Wolff Nicole , Roessner Veit , Vetter Nora C. , Buse Judith
Published: April 2021

Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.
Lipoprotein-Associated Phospholipase A2 Is a Risk Factor for Patients With Parkinson’s Disease
Authors: Wu Zubo , Wu Suyuan , Liang Tao , Wang Lin
Published: April 2021

Objective

To explore the association between lipoprotein-related phospholipase A2 (Lp-PLA2) and the risk of Parkinson’s disease (PD).

Methods

A case-control study involving 58 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected. According to the disease course and severity, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD patients was investigated using receiver’s operator characteristic curves.

Results

Lp-PLA2 level was significantly higher in the PD patients compared with the controls, and was significantly and positively correlated with the Hoehn-Yahr (H&Y) stage. The serum Lp-PLA2 level and H&Y stage of PD patients with a longer disease course were significantly higher than those with a shorter disease course. PD patients with milder conditions had significantly lower serum Lp-PLA2 levels than patients with severe conditions. Multivariable logistic regression analysis indicated higher Lp-PLA2 level was an independent risk factor of PD patients. Moreover, the area under the curve for Lp-PLA2 was 0.703, which was between those of homocysteine and serum amylase A.

Conclusion

To our knowledge, this is the first study to show that increased level of Lp-PLA2 is associated with the risk of PD. Lp-PLA2 may be used for early detection of PD, and provides an effective intervention target for clinical treatment of PD.
Cell-Type-Specific Gene Modules Related to the Regional Homogeneity of Spontaneous Brain Activity and Their Associations With Common Brain Disorders
Authors: Shen Junlin , Yang Bingbing , Xie Zhonghua , Wu Heng , Zheng Zhanye , Wang Jianhua , Wang Ping , Zhang Peng , Li Wei , Ye Zhaoxiang , Yu Chunshui
Published: April 2021

Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. The neuron-endothelial module was mainly enriched for transporter complexes, the neuron module for the synaptic membrane, the astrocyte module for amino acid metabolism, and microglial modules for leukocyte activation and ribose phosphate biosynthesis. In enrichment analyses of cell-type-specific modules for 10 common brain disorders, only the microglial module was significantly enriched for genes obtained from genome-wide association studies of multiple sclerosis (MS) and Alzheimer’s disease (AD). The ReHo of spontaneous brain activity is associated with the gene expression profiles of neurons, astrocytes, microglia and endothelial cells. The microglia-related genes associated with MS and AD may provide possible molecular substrates for ReHo abnormality in both brain disorders.
A Novel Model Based on Deep Convolutional Neural Network Improves Diagnostic Accuracy of Intramucosal Gastric Cancer (With Video)
Authors: Tang Dehua , Zhou Jie , Wang Lei , Ni Muhan , Chen Min , Hassan Shahzeb , Luo Renquan , Chen Xi , He Xinqi , Zhang Lihui , Ding Xiwei , Yu Honggang , Xu Guifang , Zou Xiaoping
Published: April 2021

Background and Aims

Prediction of intramucosal gastric cancer (GC) is a big challenge. It is not clear whether artificial intelligence could assist endoscopists in the diagnosis.

Methods

A deep convolutional neural networks (DCNN) model was developed via retrospectively collected 3407 endoscopic images from 666 gastric cancer patients from two Endoscopy Centers (training dataset). The DCNN model’s performance was tested with 228 images from 62 independent patients (testing dataset). The endoscopists evaluated the image and video testing dataset with or without the DCNN model’s assistance, respectively. Endoscopists’ diagnostic performance was compared with or without the DCNN model’s assistance and investigated the effects of assistance using correlations and linear regression analyses.

Results

The DCNN model discriminated intramucosal GC from advanced GC with an AUC of 0.942 (95% CI, 0.915–0.970), a sensitivity of 90.5% (95% CI, 84.1%–95.4%), and a specificity of 85.3% (95% CI, 77.1%–90.9%) in the testing dataset. The diagnostic performance of novice endoscopists was comparable to those of expert endoscopists with the DCNN model’s assistance (accuracy: 84.6% vs. 85.5%, sensitivity: 85.7% vs. 87.4%, specificity: 83.3% vs. 83.0%). The mean pairwise kappa value of endoscopists was increased significantly with the DCNN model’s assistance (0.430–0.629 vs. 0.660–0.861). The diagnostic duration reduced considerably with the assistance of the DCNN model from 4.35s to 3.01s. The correlation between the perseverance of effort and diagnostic accuracy of endoscopists was diminished using the DCNN model (r: 0.470 vs. 0.076).

Conclusions

An AI-assisted system was established and found useful for novice endoscopists to achieve comparable diagnostic performance with experts.
Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
Authors: Gu Xian , Zhu Ling-yu , Xu Zhen-ye , Shen Ke-ping
Published: April 2021

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.