bluuebunny/crossref_metadata_2025 huggingface dataset:
The Employment and Social Insurance Bill. III. Problems in Unemployment Insurance Administration
Authors: Stewart Bryce M.
Published: October 2022

It is a satisfaction that the unemployment insurance legislation now proposed in Canada contemplates a national insurance and placement system as against the federal-state machinery which would be established by the Social Security Bill before the United States Congress. Argument based on the evolution of unemployment insurance in other countries or on the nature of insurance must favour a national system. If the Bills being considered by the two countries are passed in substantially their present form, Canada will have outstripped the United States in unemployment insurance and placement legislation. Indeed, for some years Canada has been to the fore not only in this field but with respect to social insurance and its administration generally. The Canadian law providing for a federal-provincial employment service was passed in 1918, the corresponding Wagner-Peyser Act in the United States in 1933. Workmen's compensation, the one important form of social insurance in which the two countries have had any considerable experience, has provided a high degree of uniform protection in Canada and practically complete coverage although controlled and administered entirely by the provinces. In the United States in an experience extending over almost the same period four states still have no legislation and in the others the great differences in benefit scales, organization, and procedure result in highly dissimilar measures of protection for the citizens of the country. In both old age and mothers' allowances conditioned on a means test, a much larger proportion of the population is covered in Canada than in the United States, and with respect to the former, the government of Canada has been assisting the provinces for several years while in the United States the federal government is only now considering aid to the states.
Arctic Survey Part V. Transportation in the Canadian North
Authors: Hewetson H. W.
Published: October 2022

The development of a region can obviously not proceed faster than transportation facilities will permit. In an area of the vast extent of the Canadian northland, isolation remains the predominant characteristic in nearly all portions, and no part can expect to advance economically unless it has efficient and cheap transportation to the outside world.

The present transportation facilities in the western part of sub-arctic Canada are surprisingly good when one considers the limited volume of traffic they handle, yet the transportation routes follow in the main only the major water routes running northward. Great stretches of country to the east and west of these waterways are without transportation. However, in the present state of our knowledge there has been little if any thought of development in these large “dead” areas.

The first question to be asked, probably, is whether existing traffic can be handled adequately by the existing means of transportation. Before the war the answer would undoubtedly have been “yes.” American activities in Yukon Territory and the Mackenzie District since the United States entered the war have increased the volume of tonnage moving in the North enormously. Transportation has been improved by highway construction, the addition of railway rolling stock, water craft, and aeroplanes, and by the introduction of tractor trains. For the handling of a special commodity, oil, the Canol pipe-line has been built. Despite these improvements northern transportation is still under a strain, but is meeting its difficulties with about the same degree of success as is wartime transportation elsewhere.
Aspects of The Railway Problem III. The Senate Committee on Railways, 1938
Authors: Currie A. W.
Published: October 2022

Early in the 1938 session of Parliament the Canadian Senate appointed a Special Committee to “enquire into and report upon the best means of relieving the country from its extremely serious railway condition and financial burden consequent thereto.” After hearing extensive evidence from the officials of both railways and of the labour unions, the Committee stated that through lack of time it was unable to analyse this material in a satisfactory manner and therefore recommended that it be reappointed early in the 1939 session. It is the purpose of this article briefly to review the evidence presented and in particular to suggest lines along which further investigation by the Committee might profitably be undertaken.

The Duff Commission believed that the policy of co-operation which it espoused would lead to annual savings of at least $35,000,000, though it developed that it had never secured, or been given, detailed information on which to base this estimate (1374). The actual joint net economies after five years' trial were only $1,772,000 per annum (121).
Newfoundland, Economic and Political III. Basic Problems of Government in Newfoundland
Authors: Innis H. A.
Published: October 2022

It would be presumptuous for a Canadian to comment critically on the affairs, of Newfoundland—particularly as a native of a country which has done its share of bullying a small neighbour and of a country which can scarcely point the finger of scorn on grounds of bad government. Charges of corruption heard in Newfoundland fall on attuned Canadian ears—and it would probably not be difficult to find specific instances of scandal in the history of government in Canada which would match those of Newfoundland.

Nevertheless a student of the economic history of both countries may be forgiven for reflections suggested by comparisons and contrasts. In common with other maritime regions, Newfoundland throughout her history has faced the sea, and she has been the last to feel the effects of the pull of the North American continent. The railroad from St. John's to Port aux Basques brought her in direct touch with North America viá Sydney. Canadian bankers assumed control in the island after the crash in 1894. With the turn of the century the steel mills of Nova Scotia began to draw on the iron mines of Wabana. While British industrialism penetrated Newfoundland in the construction of paper mills, it was significant that Cornerbrook on the west coast was sold to International. Industrialism, particularly as evident in transportation, linked Newfoundland more closely to the continent, to mention only the demands for coal and oil.
Northern Ireland farm-level management factors for recurrent bovine tuberculosis herd breakdowns
Authors: Doyle L. P. , Courcier E. A. , Gordon A. W. , O'Hagan M. J. H. , Johnston P. , McAleese E. , Buchanan J. R. , Stegeman J. A. , Menzies F. D.
Published: October 2022

Bovine tuberculosis (bTB) is a chronic, infectious and zoonotic disease of domestic and wild animals caused mainly by Mycobacterium bovis. This study investigated farm management factors associated with recurrent bTB herd breakdowns (n = 2935) disclosed in the period 23 May 2016 to 21 May 2018 and is a follow-up to our 2020 paper which looked at long duration bTB herd breakdowns. A case control study design was used to construct an explanatory set of farm-level management factors associated with recurrent bTB herd breakdowns. In Northern Ireland, a Department of Agriculture Environment and Rural Affairs (DAERA) Veterinarian investigates bTB herd breakdowns using standardised guidelines to allocate a disease source. In this study, source was strongly linked to carryover of infection, suggesting that the diagnostic tests had failed to clear herd infection during the breakdown period. Other results from this study associated with recurrent bTB herd breakdowns were herd size and type (dairy herds 43% of cases), with both these variables intrinsically linked. Other associated risk factors were time of application of slurry, badger access to silage clamps, badger setts in the locality, cattle grazing silage fields immediately post-harvest, number of parcels of land the farmer associated with bTB, number of land parcels used for grazing and region of the country.
The Seasonality of Deuterium Excess in Non‐Polar Precipitation
Authors: Xia Zhengyu , Welker Jeffrey M. , Winnick Matthew J.
Published: October 2022

The deuterium excess (d‐excess) of precipitation varies seasonally at sites across the globe, an observation that has often been linked to seasonal changes in oceanic evaporation conditions, continental moisture recycling, and subcloud raindrop re‐evaporation. However, there have been very few studies to quantify and evaluate the relative importance of these processes. Here, we revisit the mechanisms of precipitation d‐excess seasonality in low‐latitudes and mid‐latitudes through a new analysis of precipitation isotope databases along with climate reanalysis products and moisture tracking models. In low‐latitudes, the raindrop re‐evaporation effect, indicated by local relative humidity, exerts a strong and prevalent control on observed d‐excess seasonality and overprints the effect of oceanic evaporation conditions. In mid‐latitudes, the effect of oceanic evaporation conditions becomes stronger and seems dominant in the observed d‐excess seasonality. However, the ultimate d‐excess signals are produced after complex modulations by several reinforcing or competing processes, including prior distillations, moisture recycling, supersaturation in snow formation, and raindrop re‐evaporation. Among these processes, substantial increases in the proportion of recycled moisture during the warm and dry season do not produce higher precipitation d‐excess in mid‐latitude continental interiors. We develop a simple seasonal water storage model to show that contributions of previously evaporated residual water storage and higher transpiration fractions may lead to relatively low d‐excess in evapotranspiration fluxes during periods of enhanced continental moisture recycling. This study underscores the ubiquitous nonconservative behavior in d‐excess throughout the water cycle, as opposed to using d‐excess as a simple tracer for remote conditions at oceanic moisture sources.
Regional Geoengineering Using Tiny Glass Bubbles Would Accelerate the Loss of Arctic Sea Ice
Authors: Webster Melinda A. , Warren Stephen G.
Published: October 2022

Arctic sea ice might be preserved if its albedo could be increased. To this end, it has been proposed to spread hollow glass microspheres (HGMs) over the ice. We assess the radiative forcing that would result, by considering the areal coverages and spectral albedos of eight representative surface types, as well as the incident solar radiation, cloud properties, and spectral radiative properties of HGMs. HGMs can raise the albedo of new ice, but new ice occurs in autumn and winter when there is little sunlight. In spring the ice is covered by high‐albedo, thick snow. In summer the sunlight is intense, and the snow melts, so a substantial area is covered by dark ponds of meltwater, which could be an attractive target for attempted brightening. However, prior studies show that wind blows HGMs to the pond edges. A thin layer of HGMs has about 10% absorptance for solar radiation, so HGMs would darken any surfaces with albedo >0.61, such as snow‐covered ice. The net result is the opposite of what was intended: spreading HGMs would warm the Arctic climate and speed sea‐ice loss. If non‐absorbing HGMs could be manufactured, and if they could be transported and distributed without contamination by dark substances, they could cool the climate. The maximum benefit would be achieved by distribution during the month of May, resulting in an annual average radiative forcing for the Arctic Ocean of −3 Wm−2 if 360 megatons of HGMs were spread onto the ice annually.
Seasonal Dynamics of Dissolved Iron on the Antarctic Continental Shelf: Late‐Fall Observations From the Terra Nova Bay and Ross Ice Shelf Polynyas
Authors: Sedwick P. N. , Sohst B. M. , O’Hara C. , Stammerjohn S. E. , Loose B. , Dinniman M. S. , Buck N. J. , Resing J. A. , Ackley S. F.
Published: October 2022

Over the Ross Sea shelf, annual primary production is limited by dissolved iron (DFe) supply. Here, a major source of DFe to surface waters is thought to be vertical resupply from the benthos, which is assumed most prevalent during winter months when katabatic winds drive sea ice formation and convective overturn in coastal polynyas, although the impact of these processes on water‐column DFe distributions has not been previously documented. We collected hydrographic data and water‐column samples for trace metals analysis in the Terra Nova Bay and Ross Ice Shelf polynyas during April–May 2017 (late austral fall). In the Terra Nova Bay polynya, we observed intense katabatic wind events, and surface mixed layer depths varied from ∼250 to ∼600 m over lateral distances <10 km; there vertical mixing was just starting to excavate the dense, iron‐rich Shelf Waters, and there was also evidence of DFe inputs at shallower depths in the water column. In the Ross Ice Shelf polynya, wind speeds were lower, mixed layers were <300 m deep, and DFe distributions were similar to previous, late‐summer observations, with concentrations elevated near the seafloor. Corresponding measurements of dissolved manganese and zinc, and particulate iron, manganese, and aluminum, suggest that deep DFe maxima and some mid‐depth DFe maxima primarily reflect sedimentary inputs, rather than remineralization. Our data and model simulations imply that vertical resupply of DFe in the Ross Sea occurs mainly during mid‐late winter, and may be particularly sensitive to changes in the timing and extent of sea ice production.
Chenier Formation Through Wave Winnowing and Tides
Authors: Tas Silke A. J. , van Maren Dirk S. , Reniers Ad J. H. M.
Published: October 2022

Cheniers are ridges consisting of coarse‐grained sediments, resting on top of the fine sediment that forms the otherwise muddy coast. In this paper, we use Delft3D to explore how cheniers are formed through wave winnowing. We identify three phases of chenier development: (a) a winnowing phase, during which mud is washed out of the seabed initially consisting of a mixture of sand and mud, (b) a sand transport phase, when the sand in the upper layer is transported onshore, and (c) a crest formation phase, during which a chenier crest rapidly develops at the landward limit of onshore sediment transport. The main mechanism driving onshore sand transport is wave asymmetry. During calm conditions, sand transport takes place within a narrow band limiting the volume of sand delivered nearshore, and therefore no chenier develops. In contrast, average storm conditions mobilize sufficient sand for a crest to develop. Our results thus reveal that chenier formation through wave winnowing does not require extreme storm conditions. Furthermore, our study showed that chenier formation through wave winnowing is a relatively slow process, with the largest time scales associated with the winnowing and sand transport. Once sufficient sand is available in the intertidal zone, the crest develops rapidly.
Variations in Phytoplankton Primary Production Driven by the Pacific Decadal Oscillation in the East/Japan Sea
Authors: Lee Dabin , Kang Jae Joong , Jo Naeun , Kim Kwanwoo , Jang Hyo Keun , Kim Myung Joon , Kim Yejin , Park Sanghoon , Son SeungHyun , Kwon Jae‐Il , Yun Mi Sun , Kang Chang‐Keun , Lee Sang Heon
Published: October 2022

The Pacific Decadal Oscillation (PDO) regime is a major factor not only for the physical properties of the ocean but also for fishery and water resources. However, only a few studies have examined the impact of the PDO on the marine ecosystem in the East/Japan Sea. Therefore, in this study, the relationship between PDO and primary production (PP), and subsequent effects on the marine ecosystem were investigated in the East/Japan Sea using satellite data sets. PDO index showed a negative relationship with sea surface temperature (SST) and the contribution of the small phytoplankton to the total PP during the study period, whereas the mixed layer depth (MLD) and the PP showed a positive relationship with PDO index. The shallower MLD during the negative PDO phase indicates that vertical mixing may be weakened due to the stronger stratification caused by the higher SST than observed during the positive PDO phase. Consequently, we hypothesized that weakened vertical mixing may reduce nutrient supply to the euphotic layer, providing small‐sized phytoplankton favored environmental conditions during the negative PDO. It is noteworthy that PDO‐induced shoaling of the MLD was mainly observed in winter, which may influence the annual PP of the following year. This study shows that the annual PP in the East/Japan Sea can be largely affected through interactions between SST, MLD and subsequent changes in nutrient regime according to the PDO regime, which subsequently affects potential fishery resources in the East/Japan Sea.
Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms
Authors: Borsini Alessandra , Merrick Blair , Edgeworth Jonathan , Mandal Gargi , Srivastava Deepak P. , Vernon Anthony C. , Nebbia Gaia , Thuret Sandrine , Pariante Carmine M.
Published: October 2022

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis. We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium). Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13. Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.
SARS-CoV-2 promotes microglial synapse elimination in human brain organoids
Authors: Samudyata  , Oliveira Ana O. , Malwade Susmita , Rufino de Sousa Nuno , Goparaju Sravan K. , Gracias Jessica , Orhan Funda , Steponaviciute Laura , Schalling Martin , Sheridan Steven D. , Perlis Roy H. , Rothfuchs Antonio G. , Sellgren Carl M.
Published: October 2022

Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure. We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synapse engulfment. To a large extent, SARS-CoV-2 exposed microglia adopt a transcriptomic profile overlapping with neurodegenerative disorders that display an early synapse loss as well as an increased incident risk after a SARS-CoV-2 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from COVID-19.
Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials
Authors: Niu Zhenyi , Jin Runsen , Zhang Yan , Li Hecheng
Published: October 2022

Lung cancer is the leading cause of cancer-related death across the world. Unlike lung adenocarcinoma, patients with lung squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved cancer patients’ outcomes, the relatively low response rate and severe adverse events hinder the clinical application of this promising treatment in LSCC. Therefore, it is of vital importance to have a better understanding of the mechanisms underlying the pathogenesis of LSCC as well as the inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions for LSCC. In this review, new insights were given about classical signaling pathways which have been proved in other cancer types but not in LSCC, including PI3K signaling pathway, VEGF/VEGFR signaling, and CDK4/6 pathway. Other signaling pathways which may have therapeutic potentials in LSCC were also discussed, including the FGFR1 pathway, EGFR pathway, and KEAP1/NRF2 pathway. Next, chromosome 3q, which harbors two key squamous differentiation markersSOX2andTP63is discussed as well as its related potential therapeutic targets. We also provided some progress of LSCC in epigenetic therapies and immune checkpoints blockade (ICB) therapies. Subsequently, we outlined some combination strategies of ICB therapies and other targeted therapies. Finally, prospects and challenges were given related to the exploration and application of novel therapeutic strategies for LSCC.
Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
Authors: Dannemann Michael , Milaneschi Yuri , Yermakovich Danat , Stiglbauer Victoria , Kariis Hanna Maria , Krebs Kristi , Friese Manuel A. , Otte Christian ,   Estonian Biobank Research Team, Esko Tõnu , Metspalu Andres , Milani Lili , Mägi Reedik , Nelis Mari , Lehto Kelli , Penninx Brenda W. J. H. , Kelso Janet , Gold Stefan M.
Published: October 2022

Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets.

Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute to pathology in modern day humans
Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants
Authors: Del Vecchio Claudia , Cracknell Daniels Bethan , Brancaccio Giuseppina , Brazzale Alessandra Rosalba , Lavezzo Enrico , Ciavarella Constanze , Onelia Francesco , Franchin Elisa , Manuto Laura , Bianca Federico , Cianci Vito , Cattelan Anna Maria , Dorigatti Ilaria , Toppo Stefano , Crisanti Andrea
Published: October 2022

Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread.
Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method
Authors: Cai Ye , Cao Huifen , Wang Fang , Zhang Yufei , Kapranov Philipp
Published: October 2022

DNA damage plays a critical role in biology and diseases; however, how different types of DNA lesions affect cellular functions is far from clear mostly due to the paucity of high-resolution methods that can map their locations in complex genomes, such as those of mammals. Here, we present the development and validation of SSiNGLe-AP method, which can map a common type of DNA damage, abasic (AP) sites, in a genome-wide and high-resolution manner. We apply this method to six different tissues of mice with different ages and human cancer cell lines. We find a nonrandom distribution of AP sites in the mammalian genome that exhibits dynamic enrichment at specific genomic locations, including single-nucleotide hotspots, and is significantly influenced by gene expression, age and tissue type in particular. Overall, these results suggest that we are only starting to understand the true complexities in the genomic patterns of DNA damage.
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes
Authors: Wei Wei , Schon Katherine R. , Elgar Greg , Orioli Andrea , Tanguy Melanie , Giess Adam , Tischkowitz Marc , Caulfield Mark J. , Chinnery Patrick F.
Published: October 2022

DNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event—the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation1–3. Here we analyse whole-genome sequences from 66,083 people—including 12,509 people with cancer—and demonstrate the ongoing transfer of mitochondrial DNA into the nucleus, contributing to a complex NUMT landscape. More than 99% of individuals had at least one of 1,637 different NUMTs, with 1 in 8 individuals having an ultra-rare NUMT that is present in less than 0.1% of the population. More than 90% of the extant NUMTs that we evaluated inserted into the nuclear genome after humans diverged from apes. Once embedded, the sequences were no longer under the evolutionary constraint seen within the mitochondrion, and NUMT-specific mutations had a different mutational signature to mitochondrial DNA. De novo NUMTs were observed in the germline once in every 104 births and once in every 103 cancers. NUMTs preferentially involved non-coding mitochondrial DNA, linking transcription and replication to their origin, with nuclear insertion involving multiple mechanisms including double-strand break repair associated with PR domain zinc-finger protein 9 (PRDM9) binding. The frequency of tumour-specific NUMTs differed between cancers, including a probably causal insertion in a myxoid liposarcoma. We found evidence of selection against NUMTs on the basis of size and genomic location, shaping a highly heterogenous and dynamic human NUMT landscape.
Tracing the oomycete pathogen Saprolegnia parasitica in aquaculture and the environment
Authors: Pavić Dora , Grbin Dorotea , Hudina Sandra , Prosenc Zmrzljak Uršula , Miljanović Anđela , Košir Rok , Varga Filip , Ćurko Josip , Marčić Zoran , Bielen Ana
Published: October 2022

Saprolegnia parasitica causes saprolegniosis, a disease responsible for significant economic losses in aquaculture and declines of fish populations in the wild, but the knowledge of its distribution and prevalence in the environment is limited. We developed a fast, sensitive and specific S. parasitica droplet digital PCR (ddPCR) assay and demonstrated its applicability for the detection and quantification of the pathogen in environmental samples: swab DNA collected from the host (trout skin, surface of eggs) and environmental DNA extracted from water. The developed assay was used to assess how abiotic (i.e. physico-chemical parameters of the water) and biotic (health status of the host) factors influence the S. parasitica load in the environment. The pathogen load in water samples was positively correlated with some site-specific abiotic parameters such as electrical conductivity (EC) and calcium, while fluorides were negatively correlated, suggesting that physico-chemical parameters are important for determining S. parasitica load in natural waters. Furthermore, skin swabs of injured trout had significantly higher pathogen load than swabs collected from healthy fish, confirming that S. parasitica is a widespread opportunistic pathogen. Our results provide new insights into various environmental factors that influence the distribution and abundance of S. parasitica.
Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis
Authors: Deshayes Samuel , Fraisse Thibault , Fellahi Soraya , Steichen Olivier , Savey Léa , Turlin Bruno , Munteanu Mona , Aouba Achille , Bourguiba Rim , Hentgen Véronique , Faintuch Jean-Manuel , Giurgea Irina , Grateau Gilles , Bastard Jean-Philippe , Georgin-Lavialle Sophie
Published: October 2022

Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity.
Age at first birth and risk of urinary incontinence after delivery: a dose–response meta-analysis
Authors: Ren Yongcheng , Hu Qing , Zou Haiyin , Xue Meifang , Tian Xinjie , Cao Fuqun , Yang Lei
Published: October 2022

Studies investigating the impact of age at first birth on urinary incontinence after delivery have reached inconsistent conclusions. We performed this systematic review and meta-analysis of studies assessing the risk of urinary incontinence after delivery, regardless of the type, with age at first birth. MEDLINE via PubMed and Web of science databases were searched up to March 13, 2021. Restricted cubic splines were used to model the dose–response association. Twelve publications were included in this meta-analysis. The summary odds ratio (OR) and 95% confidence interval (CI) per 1-year increase in age at first birth were 1.01 (95% CI (0.99, 1.02)) for urinary incontinence (America: 1.00 (0.99, 1.00); Europe: 1.03 (1.00, 1.06); Asian: 0.99 (0.89, 1.10)). A non-linear dose–response (Pnonlinearity < 0.01) indicated that age at first birth older than 32 (P < 0.05) increases the risk of urinary incontinence. First birth before age 32 make decrease the risk of urinary incontinence after delivery.
Res﻿earch on dust dispersion law of fully mechanized mining faces under different inclinations and tracking closed dust control method
Authors: Zhou Gang , Kong Yang , Meng Qunzhi , Jiang Bingyou , Liu Yongwei , Li Gang , Sun Biao , Wang Jinli , Yan Dong , Li Zhenhua
Published: October 2022

Based on the gas–solid two-phase flow theory, numerical simulation of the dust dispersion law of fully mechanized mining work under different inclination angles and comparative analysis of field-measured data show that with the increase of working face inclination, the inclination of airflow into the unmined zone increases from 25° to 50° and the maximum wind speed increases from 2.16 to 2.25 m/s after the mixing of cutting turbulent wind and system ventilation. Meanwhile, the range of high-concentration dust clusters, suspension time, lateral migration intensity, and deposition zone increase to varying degrees; dust clusters increases from 62.02 to 202.46 m3. When X < 53.96 m, the dust concentration in the sidewalk-breathing zone shows a sine function with the length of the working face, and when X ≥ 53.96 m, it satisfies the exponential decay function. Based on this, the tracking closed dust control technology is proposed. Combining the offset angle of the airflow and t the gathering position of dust mass, the wind curtain angle and air velocity are automatically controlled to ensure that the dust is restricted to one side of the cable trough.
Protein interaction, cytotoxic, transcriptomic and proteomic responses to structurally distinct EPAC1 activators in HUVECs
Authors: Wiejak Jolanta , Luchowska-Stańska Urszula , Wang Pingyuan , Zhou Jia , Maffia Pasquale , Morgan David , Barker Graeme , Yarwood Stephen J.
Published: October 2022

The N-acylsulfonamide derivative, I942, represents the first non-cyclic nucleotide partial agonist of EPAC1. This was soon followed by the identification of the I942 analogues, PW0381, PW0521 and PWO577 and a series of benzofuran oxoacetic acid EPAC1 activators, SY006, SY007 and SY009. Protein interaction, cytotoxicity and EPAC1 activation assays applied here identify PWO577 and SY007 as being effective EPAC1 binders that are well tolerated in HUVECs at concentrations greater than 100 μM and up to 48 h incubation and are effective activators of transfected EPAC1 in U2OS cells. Using RNAseq in HUVECs we show that PWO577 and SY007 regulate approximately 11,000 shared genes, with only few differential gene changes being “off-target”. The genes significantly regulated by both PWO577 and SY007 included a subset of genes normally associated with endothelial activation, including ICAM1, MMP1 and CCL2. Of these, only the expression of MMP1 was markedly increased at the protein level, as determined by LC–MS-based proteomics. Both PWO577 and SY007 suppressed IL-6-induced STAT3 activation and associated downstream gene expression, including inhibition of SOCS3, STAT3, IL6ST and JAK3 genes. Together these results demonstrate the utility of structurally distinct, specific and non-toxic EPAC1 activators. Future modifications will be aimed at eliminating the few noted off-target effects.
Structural measurement of electron-phonon coupling and electronic thermal transport across a metal-semiconductor interface
Authors: Jo Wonhyuk , Kee Jungyun , Kim Kooktea , Landahl Eric C. , Longbons Grace , Walko Donald A. , Wen Haidan , Lee Dong Ryeol , Lee Sooheyong
Published: October 2022

Scattering of energetic charge carriers and their coupling to lattice vibrations (phonons) in dielectric materials and semiconductors are crucial processes that determine the functional limits of optoelectronics, photovoltaics, and photocatalysts. The strength of these energy exchanges is often described by the electron-phonon coupling coefficient, which is difficult to measure due to the microscopic time- and length-scales involved. In the present study, we propose an alternate means to quantify the coupling parameter along with thermal boundary resistance and electron conductivity by performing a high angular-resolution time-resolved X-ray diffraction measurement of propagating lattice deformation following laser excitation of a nanoscale, polycrystalline metal film on a semiconductor substrate. Our data present direct experimental evidence for identifying the ballistic and diffusive transport components occurring at the interface, where only the latter participates in thermal diffusion. This approach provides a robust measurement that can be applied to investigate microscopic energy transport in various solid-state materials.
Spectral characteristics of gold nanoparticle doped optical fibre under axial strain
Authors: Wang Xiang , Benedictus Rinze , Groves Roger M.
Published: October 2022

Nanoparticle (NP) doping of optical fibres can be used to increase the intensity of the backscattered light used for distributed strain sensing and has shown the advantages of high precision strain detection and multiplex sensing experimentally. However, the backscatter spectral characteristics of NP-doped optical fibres have not been described even though they are quite different from the spectra from fibre Bragg gratings (FBGs) or commercial single mode fibres. In this paper, gold NPs, used as the contrast agent in the optical fibre to increase the intensity of the backscattered light, were investigated from the aspect of their spectra. A single scattering model with Mie theory and an effective refractive index (RI) model were used to evaluate the backscattered light spectra and the Monte Carlo Method was used for seeding NPs. The results showed that the strain responsivity of gold-NP doped fibres with low volume ratio doping (single scattering restriction) are close to FBGs and commercial fibres. High volume ratios of gold NP doping increase the imaginary part of the RI of the optical fibre, which has a significant influence on the spectra in the wavenumber domain. These theoretical insights may promote the future engineering design of NP-doped fibre sensors.
Preparation and characterization of acrylic resins with bioactive glasses
Authors: Raszewski Zbigniew , Chojnacka Katarzyna , Mikulewicz Marcin
Published: October 2022

This study aimed to prepare a bioactive acrylic material by adding different types of glasses. Commercially available polymerized acrylic resin was mixed with 10% of four different types of glasses in the powder form and cured. Flexural strength, sorption, and solubility of the samples were tested according to ISO 20795-1:2013. The total number of samples used in the tests were 60. The materials were placed in artificial saliva of pH 4 and 7, and elution was performed for 0, 1, 28, and 42 days. The collected samples were analyzed using inductively coupled plasma atomic emission spectrometry to detect Ca, P, and Si ions and using ion chromatography to detect F ions. The materials obtained after modification with glasses showed lower compressive strength compared with pure polymethyl methacrylate but met the standard requirements. Two glass types showed higher solubility values compared with the value defined by the ISO standard. Biomin C and S53P4 released Ca, P, and Si ions, respectively, after 42 days in artificial saliva. Acrylic resins modified with 10% Biomin C and S53P4 glasses can be a valuable source of Ca and P ions under acid conditions for 28 and 42 days.
The evolution of parental care in salamanders
Authors: Vági Balázs , Marsh Daniel , Katona Gergely , Végvári Zsolt , Freckleton Robert P. , Liker András , Székely Tamás
Published: October 2022

Complex parenting has been proposed to contribute to the evolutionary success of vertebrates. However, the evolutionary routes to complex parenting and the role of parenting in vertebrate diversity are still contentious. Although basal vertebrates provide clues to complex reproduction, these are often understudied. Using 181 species that represent all major lineages of an early vertebrate group, the salamanders and newts (Caudata, salamanders henceforth) here we show that fertilisation mode is tied to parental care: male-only care occurs in external fertilisers, whereas female-only care exclusively occurs in internal fertilisers. Importantly, internal fertilisation opens the way to terrestrial reproduction, because fertilised females are able to deposit their eggs on land, and with maternal care provision, the eggs could potentially develop outside the aquatic environment. Taken together, our results of a semi-aquatic early vertebrate group propose that the diversity and follow-up radiation of terrestrial vertebrates are inherently associated with a complex social behaviour, parenting.
Gene mapping methodology powered by induced genome rearrangements
Authors: Yone Hideyuki , Kono Hiromitsu , Hirai Hayato , Ohta Kunihiro
Published: October 2022

Phenotypic variation occurs through genome rearrangements and mutations in certain responsible genes; however, systematic gene identification methodologies based on genome rearrangements have not been fully established. Here, we explored the loci responsible for the given phenotype using the TAQing system and compared it with a conventional mutagenesis-based method. Two yeast strains with different genetic backgrounds and flocculation phenotypes were fused and genomic rearrangements were induced by transient DNA breaks. Then, selection pressure was applied and multiple mutants were generated, showing different flocculation abilities. We also raised mutants with altered cohesiveness due to spontaneous mutations during long-term recursive passages of haploid strains without TAQing treatment. Comparative genomic analysis of the TAQed mutants revealed three chromosomal regions harboring pivotal flocculation genes, whereas conventional mutagenesis generated a more diverse list of candidate loci after prolonged selection. The combined use of these approaches will accelerate the identification of genes involved in complex phenotypes.
Potential link between high FIB-4 score and chronic kidney disease in metabolically healthy men
Authors: Kuma Akihiro , Mafune Kosuke , Uchino Bungo , Ochiai Yoko , Miyamoto Tetsu , Kato Akihiko
Published: October 2022

Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or proteinuria) and a habit of alcohol consumption were excluded. The cut-off FIB-4 score was 1.30, indicating increased risk of liver fibrosis. Overall, 5353 participants (men only) were analyzed without exclusion criteria. After propensity score matching, high FIB-4 score (≥ 1.30) was not an independent risk factor for incident CKD (odds ratio [OR] 1.57; 95% confidence interval [CI] 0.97–2.56). However, high FIB-4 score was a significant risk factor for CKD in non-obese (OR 1.92; 95% CI 1.09–3.40), non-hypertensive (OR 2.15; 95% CI 1.16–3.95), or non-smoking (OR 1.88; 95% CI 1.09–3.23) participants. In these participants, FIB-4 score was strongly associated with eGFR decline in the multiple linear regression analysis (β = − 2.8950, P = 0.011). Therefore, a high FIB-4 score may be significantly associated with CKD incidence after 5 years in metabolically healthy participants.
Investigating the rate of skeletal muscle atrophy in men and women in the intensive care unit: a prospective observational study
Authors: Wu Ruo-Yan , Sung Wei-Hung , Cheng Hui-Chen , Yeh Huan-Jui
Published: October 2022

Muscle atrophy greatly affects the prognosis of patients in the intensive care unit, but the rate of change remains unclear. In this prospective observational study, we used ultrasound to measure the change in muscle thickness of the rectus femoris (RF) and vastus intermedius (VI) in 284 patients who were admitted to the SICU of Taoyuan General Hospital between January 1 and June 30, 2020. Patients were excluded if there is a wound at the right thigh which hinders the ultrasonography probe from placing. Daily rates of muscle atrophy were calculated using linear analysis and the ratios of change were plotted against the period of hospitalization. Patient characteristics were adjusted using propensity score matching and differences between men and women were analyzed. A linear mixed model was used to calculate the influence of other factors on muscle loss. The average daily atrophy rates of the RF and VI were 0.84% and 0.98%, respectively. The rate of atrophy was the highest in the third and fourth weeks. Daily atrophy rates of the RF and VI were approximately three times higher in women than in men. Protective factors of muscle atrophy included higher BMI and lower initial thickness of the RF and VI. Our study depicts the trend of muscle atrophy in the ICU and suggests more discussion in prevention to be conducted especially for women.