bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of ChvG-ChvI regulon by cell wall stress confers resistance to β-lactam antibiotics and initiates surface spreading in Agrobacterium tumefaciens
Authors: Williams Michelle A. , Bouchier Jacob M. , Mason Amara K. , Brown Pamela J. B.
Published: December 2022

A core component of nearly all bacteria, the cell wall is an ideal target for broad spectrum antibiotics. Many bacteria have evolved strategies to sense and respond to antibiotics targeting cell wall synthesis, especially in the soil where antibiotic-producing bacteria compete with one another. Here we show that cell wall stress caused by both chemical and genetic inhibition of the essential, bifunctional penicillin-binding protein PBP1a prevents microcolony formation and activates the canonical host-invasion two-component system ChvG-ChvI in Agrobacterium tumefaciens. Using RNA-seq, we show that depletion of PBP1a for 6 hours results in a downregulation in transcription of flagellum-dependent motility genes and an upregulation in transcription of type VI secretion and succinoglycan biosynthesis genes, a hallmark of the ChvG-ChvI regulon. Depletion of PBP1a for 16 hours, results in differential expression of many additional genes and may promote a stress response, resembling those of sigma factors in other bacteria. Remarkably, the overproduction of succinoglycan causes cell spreading and deletion of the succinoglycan biosynthesis gene exoA restores microcolony formation. Treatment with cefsulodin phenocopies depletion of PBP1a and we correspondingly find that chvG and chvI mutants are hypersensitive to cefsulodin. This hypersensitivity only occurs in response to treatment with β-lactam antibiotics, suggesting that the ChvG-ChvI pathway may play a key role in resistance to antibiotics targeting cell wall synthesis. Finally, we provide evidence that ChvG-ChvI likely has a conserved role in conferring resistance to cell wall stress within the Alphaproteobacteria that is independent of the ChvG-ChvI repressor ExoR.
RAD18 opposes transcription-associated genome instability through FANCD2 recruitment
Authors: Wells James P. , Chang Emily Yun-Chia , Dinatto Leticia , White Justin , Ryall Stephanie , Stirling Peter C.
Published: December 2022

DNA replication is a vulnerable time for genome stability maintenance. Intrinsic stressors, as well as oncogenic stress, can challenge replication by fostering conflicts with transcription and stabilizing DNA:RNA hybrids. RAD18 is an E3 ubiquitin ligase for PCNA that is involved in coordinating DNA damage tolerance pathways to preserve genome stability during replication. In this study, we show that RAD18 deficient cells have higher levels of transcription-replication conflicts and accumulate DNA:RNA hybrids that induce DNA double strand breaks and replication stress. We find that these effects are driven in part by failure to recruit the Fanconi Anemia protein FANCD2 at difficult to replicate and R-loop prone genomic sites. FANCD2 activation caused by splicing inhibition or aphidicolin treatment is critically dependent on RAD18 activity. Thus, we highlight a RAD18-dependent pathway promoting FANCD2-mediated suppression of R-loops and transcription-replication conflicts.
The two-component system ChvGI maintains cell envelope homeostasis in Caulobacter crescentus
Authors: Quintero-Yanes Alex , Mayard Aurélie , Hallez Régis
Published: December 2022

Two-component systems (TCS) are often used by bacteria to rapidly assess and respond to environmental changes. The ChvG/ChvI (ChvGI) TCS conserved in α-proteobacteria is known for regulating expression of genes related to exopolysaccharide production, virulence and growth. The sensor kinase ChvG autophosphorylates upon yet unknown signals and phosphorylates the response regulator ChvI to regulate transcription. Recent studies in Caulobacter crescentus showed that chv mutants are sensitive to vancomycin treatment and fail to grow in synthetic minimal media. In this work, we identified the osmotic imbalance as the main cause of growth impairment in synthetic minimal media. We also determined the ChvI regulon and found that ChvI regulates cell envelope architecture by controlling outer membrane, peptidoglycan assembly/recycling and inner membrane proteins. In addition, we found that ChvI phosphorylation is also activated upon antibiotic treatment with vancomycin. We also challenged chv mutants with other cell envelope related stress and found that treatment with antibiotics targeting transpeptidation of peptidoglycan during cell elongation impairs growth of the mutant. Finally, we observed that the sensor kinase ChvG relocates from a patchy-spotty distribution to distinctive foci after transition from complex to synthetic minimal media. Interestingly, this pattern of (re)location has been described for proteins involved in cell growth control and peptidoglycan synthesis upon osmotic shock. Overall, our data support that the ChvGI TCS is mainly used to monitor and respond to osmotic imbalances and damages in the peptidoglycan layer to maintain cell envelope homeostasis.
Denisovan introgression has shaped the immune system of present-day Papuans
Authors: Vespasiani Davide M. , Jacobs Guy S. , Cook Laura E. , Brucato Nicolas , Leavesley Matthew , Kinipi Christopher , Ricaut François-Xavier , Cox Murray P. , Gallego Romero Irene
Published: December 2022

Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan individuals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic diversity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans.
Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome
Authors: Poll Sarah R. , Martin Renan , Wohler Elizabeth , Partan Elizabeth S. , Walek Elizabeth , Salman Shaima , Groepper Daniel , Kratz Lisa , Cernach Mirlene , Jesus-Garcia Reynaldo , Haldeman-Englert Chad , Choi Yoon Jae , Morris Carol D. , Cohen Bernard , Hoover-Fong Julie , Valle David , Semenza Gregg L. , Sobreira Nara L. M.
Published: December 2022

Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.
Identification of C. elegans ASNA-1 domains and tissue requirements that differentially influence platinum sensitivity and growth control
Authors: Raj Dorota , Podraza-Farhanieh Agnieszka , Gallego Pablo , Kao Gautam , Naredi Peter
Published: December 2022

ASNA1 plays an essential role in cisplatin chemotherapy response, type 2 diabetes, and heart disease. It is also an important biomarker in the treatment response of many diseases. Biochemically, ASNA1 has two mutually exclusive redox-modulated roles: a tail-anchored protein (TAP) targeting function in the reduced state and a holdase/chaperone function in the oxidized state. Assigning biochemical roles of mammalian ASNA1 to biomedical functions is crucial for successful therapy development. Our previous work showed the relevance of the C. elegans ASNA-1 homolog in modeling cisplatin response and insulin secretion. Here we analyzed two-point mutants in highly conserved residues in C. elegans ASNA-1 and determined their importance in separating the cisplatin response function from its roles in insulin secretion. asna-1(ΔHis164) and asna-1(A63V) point mutants, which both preferentially exist in the oxidized state, displayed cisplatin sensitivity phenotype as well as TAP insertion defect but not an insulin secretion defect. Further, using targeted depletion we analyzed the tissue requirements of asna-1 for C. elegans growth and development. Somatic depletion of ASNA-1 as well as simultaneous depletion of ASNA-1 in neurons and intestines resulted in an L1 arrest. We concluded that, targeting single residues in ASNA-1 affecting Switch I/Switch II domain function, in comparison to complete knockdown counteracted cisplatin resistance without jeopardizing other important biological functions. Taken together, our study shows that effects on health caused by ASNA1 mutations can have different biochemical bases.
Homologous chromosomes are stably conjoined for Drosophila male meiosis I by SUM, a multimerized protein assembly with modules for DNA-binding and for separase-mediated dissociation co-opted from cohesin
Authors: Kabakci Zeynep , Reichle Heidi E. , Lemke Bianca , Rousova Dorota , Gupta Samir , Weber Joe , Schleiffer Alexander , Weir John R. , Lehner Christian F.
Published: December 2022

For meiosis I, homologous chromosomes must be paired into bivalents. Maintenance of homolog conjunction in bivalents until anaphase I depends on crossovers in canonical meiosis. However, instead of crossovers, an alternative system achieves homolog conjunction during the achiasmate male meiosis of Drosophila melanogaster. The proteins SNM, UNO and MNM are likely constituents of a physical linkage that conjoins homologs in D. melanogaster spermatocytes. Here, we report that SNM binds tightly to the C-terminal region of UNO. This interaction is homologous to that of the cohesin subunits stromalin/Scc3/STAG and α-kleisin, as revealed by sequence similarities, structure modeling and cross-link mass spectrometry. Importantly, purified SU_C, the heterodimeric complex of SNM and the C-terminal region of UNO, displayed DNA-binding in vitro. DNA-binding was severely impaired by mutational elimination of positively charged residues from the C-terminal helix of UNO. Phenotypic analyses in flies fully confirmed the physiological relevance of this basic helix for chromosome-binding and homolog conjunction during male meiosis. Beyond DNA, SU_C also bound MNM, one of many isoforms expressed from the complex mod(mdg4) locus. This binding of MNM to SU_C was mediated by the MNM-specific C-terminal region, while the purified N-terminal part common to all Mod(mdg4) isoforms multimerized into hexamers in vitro. Similarly, the UNO N-terminal domain formed tetramers in vitro. Thus, we suggest that multimerization confers to SUM, the assemblies composed of SNM, UNO and MNM, the capacity to conjoin homologous chromosomes stably by the resultant multivalent DNA-binding. Moreover, to permit homolog separation during anaphase I, SUM is dissociated by separase, since UNO, the α-kleisin-related protein, includes a separase cleavage site. In support of this proposal, we demonstrate that UNO cleavage by tobacco etch virus protease is sufficient to release homolog conjunction in vivo after mutational exchange of the separase cleavage site with that of the bio-orthogonal protease.
Drug resistance mechanisms create targetable proteostatic vulnerabilities in Her2+ breast cancers
Authors: Singh Navneet , Romick-Rosendale Lindsey , Watanabe-Chailland Miki , Privette Vinnedge Lisa M. , Komurov Kakajan
Published: December 2022

Oncogenic kinase inhibitors show short-lived responses in the clinic due to high rate of acquired resistance. We previously showed that pharmacologically exploiting oncogene-induced proteotoxic stress can be a viable alternative to oncogene-targeted therapy. Here, we performed extensive analyses of the transcriptomic, metabolomic and proteostatic perturbations during the course of treatment of Her2+ breast cancer cells with a Her2 inhibitor covering the drug response, resistance, relapse and drug withdrawal phases. We found that acute Her2 inhibition, in addition to blocking mitogenic signaling, leads to significant decline in the glucose uptake, and shutdown of glycolysis and of global protein synthesis. During prolonged therapy, compensatory overexpression of Her3 allows for the reactivation of mitogenic signaling pathways, but fails to re-engage the glucose uptake and glycolysis, resulting in proteotoxic ER stress, which maintains the protein synthesis block and growth inhibition. Her3-mediated cell proliferation under ER stress during prolonged Her2 inhibition is enabled due to the overexpression of the eIF2 phosphatase GADD34, which uncouples protein synthesis block from the ER stress response to allow for active cell growth. We show that this imbalance in the mitogenic and proteostatic signaling created during the acquired resistance to anti-Her2 therapy imposes a specific vulnerability to the inhibition of the endoplasmic reticulum quality control machinery. The latter is more pronounced in the drug withdrawal phase, where the de-inhibition of Her2 creates an acute surge in the downstream signaling pathways and exacerbates the proteostatic imbalance. Therefore, the acquired resistance mechanisms to oncogenic kinase inhibitors may create secondary vulnerabilities that could be exploited in the clinic.
Does government institutional reform deter corporate tax evasion? Evidence from China
Authors: Xu Junbing , Zhu Minling , Song Shengying , Wu Yunxi
Published: December 2022

Exploiting the quasi-natural experiment of the social insurance collection system reform implemented in China in 2000, based on data from China’s industrial enterprise database from 1998 to 2006, we use the difference-in-differences method to test the impact of changing the social insurance collection institution on corporate tax evasion. We find that changing the social insurance collection institution from the social security department to the local tax department significantly deters corporate tax evasion. A series of robustness tests also support this conclusion. The reason is changing the social insurance collection institution to the local tax department increases its’ social insurance information of the enterprise, and reduces the information asymmetry between the enterprise and the collection institution. Furthermore, we find that the impact of changing the social insurance collection institution on corporate tax evasion is more evident in the samples of labor-intensive enterprises, low labor cost enterprises, and enterprises under the jurisdiction of the local tax department. These results indicate that government institutional reform is a valid way to reduce the information asymmetry between the government and enterprises, which will finally deter corporate tax evasion.
Physical activity, balance, and bicycling in older adults
Authors: Baughn Maya , Arellano Victor , Hawthorne-Crosby Brieanna , Lightner Joseph S. , Grimes Amanda , King Gregory
Published: December 2022

Falls are a critical public health issue among older adults. One notable factor contributing to falls in older adults is a deterioration of the structures supporting balance and overall balance control. Preliminary evidence suggests older adults who ride a bicycle have better balance than those who do not. Cycling may be an effective intervention to prevent falls among older adults. This study aims to objectively measure the relationship between bicycling, physical activity, and balance for older adults. Older adult cyclists (n = 19) and non-cyclists (n = 27) were recruited to (1) complete a survey that assessed demographics; (2) wear an accelerometer for 3 weeks to objectively assess physical activity; and (3) complete balance-related tasks on force platforms. Mann-Whitney U-tests were performed to detect differences in balance and physical activity metrics between cyclists and non-cyclists. Cyclists were significantly more physically active than non-cyclists. Cyclists, compared to non-cyclists, exhibited differences in balance-related temporospatial metrics and long-range temporal correlations that suggest a more tightly regulated postural control strategy that may relate to higher stability. Cycling was observed to correlate more strongly with balance outcomes than other physical activity. Taken together, these results demonstrate the possible implications for cycling as an effective intervention to improve balance and reduce fall risk.
Can North American animal poison control center call data provide early warning of outbreaks associated with contaminated pet food? Using the 2007 melamine pet food contamination incident as a case study
Authors: Swirski Alexandra L. , Pearl David L. , Berke Olaf , O’Sullivan Terri L.
Published: December 2022

The 2007 melamine pet food contamination incident highlighted the need for enhanced reporting of toxicological exposures and development of a national quantitative disease surveillance system for companion animals. Data from poison control centers, such as the Animal Poison Control Center (APCC), may be useful for conducting real-time surveillance in this population. In this study, we explored the suitability of APCC call data for early warning of toxicological incidents in companion animal populations by using a-priori knowledge of the melamine-related nephrotoxicosis outbreak. Patient and household-level information regarding possible toxicological exposures in dogs and cats reported to the APCC from 2005 to 2007, inclusive, were extracted from the APCC’s AnTox database. These data were used to examine the impact of surveillance outcome, statistical methodology, analysis level, and call source on the ability to detect the outbreak prior to the voluntary recall issued by the pet food manufacturer. Retrospective Poisson temporal scan tests were applied for each combination of outcome, method, level, and call source. The results showed that month-adjusted scans using syndromic data may have been able to help detect the outbreak up to two months prior to the voluntary recall although the success of these methods varied across call sources. We also demonstrated covariate month-adjustment can lead to vastly different results based on the surveillance outcome and call source to which it is applied. This illustrates care should be taken prior to arbitrarily selecting a surveillance outcome and statistical model for surveillance efforts and warns against ignoring the impacts of call source or key covariates when applying quantitative surveillance methods to APCC call data since these factors can lead to very different results. This study provides further evidence that APCC call data may be useful for conducting surveillance in the US companion animal population and further exploratory analyses and validation studies are warranted.
Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD
Authors: Dagher Rania , Fogel Paul , Wang Jingya , Soussan David , Chiang Chia-Chien , Kearley Jennifer , Muthas Daniel , Taillé Camille , Berger Patrick , Bourdin Arnaud , Chenivesse Cécile , Leroy Sylvie , Anderson Gary , Humbles Alison A. , Aubier Michel , Kolbeck Roland , Pretolani Marina ,   on behalf of the COBRA Consortium
Published: December 2022

Objective

Novel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of 1305 proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology.

Methods

Serum samples were collected from 241 COPD subjects in the multicenter French Cohort of Bronchial obstruction and Asthma to measure the expression of 1305 proteins using SOMAscan proteomic platform. Clustering of the proteomics was applied to identify disease subtypes and their functional annotation and association with key clinical parameters were examined. Cluster findings were revalidated during a follow-up visit, and compared to those obtained in a group of 47 COPD patients included in the Melbourne Longitudinal COPD Cohort.

Results

Unsupervised clustering identified two clusters within COPD subjects at inclusion. Cluster 1 showed elevated levels of factors contributing to tissue injury, whereas Cluster 2 had higher expression of proteins associated with enhanced immunity and host defense, cell fate, remodeling and repair and altered metabolism/mitochondrial functions. Patients in Cluster 2 had a lower incidence of exacerbations, unscheduled medical visits and prevalence of emphysema and diabetes. These protein expression patterns were conserved during a follow-up second visit, and substanciated, by a large part, in a limited series of COPD patients. Further analyses identified a signature of 15 proteins that accurately differentiated the two COPD clusters at the 2 visits.

Conclusions

This study provides insights into COPD heterogeneity and suggests that overexpression of factors involved in lung immunity/host defense, cell fate/repair/ remodelling and mitochondrial/metabolic activities contribute to better clinical outcomes. Hence, high throughput proteomic assay offers a powerful tool for identifying COPD endotypes and facilitating targeted therapies.
Three novel bird strike likelihood modelling techniques: The case of Brisbane Airport, Australia
Authors: Andrews Robert , Bevrani Bayan , Colin Brigitte , Wynn Moe T. , ter Hofstede Arthur H. M. , Ring Jackson
Published: December 2022

The risk posed by wildlife to air transportation is of great concern worldwide. In Australia alone, 17,336 bird-strike incidents and 401 animal-strike incidents were reported to the Air Transport Safety Board (ATSB) in the period 2010-2019. Moreover, when collisions do occur, the impact can be catastrophic (loss of life, loss of aircraft) and involve significant cost to the affected airline and airport operator (estimated at globally US$1.2 billion per year). On the other side of the coin, civil aviation, and airport operations have significantly affected bird populations. There has been an increasing number of bird strikes, generally fatal to individual birds involved, reported worldwide (annual average of 12,219 reported strikes between 2008-2015 being nearly double the annual average of 6,702 strikes reported 2001-2007) (ICAO, 2018). Airport operations including construction of airport infrastructure, frequent take-offs and landings, airport noise and lights, and wildlife hazard management practices aimed at reducing risk of birdstrike, e.g., spraying to remove weeds and invertebrates, drainage, and even direct killing of individual hazard species, may result in habitat fragmentation, population decline, and rare bird extinction adjacent to airports (Kelly T, 2006; Zhao B, 2019; Steele WK, 2021). Nevertheless, there remains an imperative to continually improve wildlife hazard management methods and strategies so as to reduce the risk to aircraft and to bird populations. Current approved wildlife risk assessment techniques in Australia are limited to ranking of identified hazard species, i.e., are ‘static’ and, as such, do not provide a day-to-day risk/collision likelihood. The purpose of this study is to move towards a dynamic, evidence-based risk assessment model of wildlife hazards at airports. Ideally, such a model should be sufficiently sensitive and responsive to changing environmental conditions to be able to inform both short and longer term risk mitigation decisions. Challenges include the identification and quantification of contributory risk factors, and the selection and configuration of modelling technique(s) that meet the aforementioned requirements. In this article we focus on likelihood of bird strike and introduce three distinct, but complementary, assessment techniques, i.e.,Algebraic,Bayesian, andClustering (ABC) for measuring the likelihood of bird strike in the face of constantly changing environmental conditions. TheABCtechniques are evaluated using environment and wildlife observations routinely collected by the Brisbane Airport Corporation (BAC) wildlife hazard management team. Results indicate that each of the techniques meet the requirements of providing dynamic, realistic collision risks in the face of changing environmental conditions.
Effects of brown seaweed extract, silicon, and selenium on fruit quality and yield of tomato under different substrates
Authors: Jalali Peyman , Roosta Hamid Reza , Khodadadi Mohsen , Torkashvand Ali Mohammadi , Jahromi Marzieh Ghanbari
Published: December 2022

Tomatoes (Lycopersicun esculentum L.) are an important group of vegetable crops that have high economical and nutritional value. The use of fertilizers and appropriate substrates is one of the important strategies that can assist in increasing the yield and quality of fruits. The present study aimed to investigate the effects of exogenous seaweed extract (Nizamuddinia zanardinii), silicon (Na2SiO3), and selenium (Na2SeO3) on quality attributes and fruit yield (FY) of tomato under palm peat + perlite and coco peat + perlite substrates. Seaweed extract significantly improved several of the fruit quality attributes such as total carbohydrate content, total soluble solids (TSS), and pH as well as the FY. The results showed that silicon (Si) (75 mg) was the best foliar spray treatment to enhance the fruit firmness (30.46 N), fruit volume (196.8 cm3), and FY (3320.5 g). The highest amount of plant yield (3429.33 g) was obtained by the interaction effects of silicon (75 mg L-1) under the effect of palm peat. The use of selenium (Se) led to improvements in flavor index (TSS/TA). Also, the application of palm peat + perlite substrate caused an increase in vitamin C (16.62 mg/100g FW), compared to other substrates (14.27 mg/100g FW). The present study suggested that foliar spray with seaweed extract and Si had beneficial effects on the quality and FY of tomatoes. Also, the palm peat substrate can be used as a good alternative to the coco peat substrate in the hydroponic system.
A quantitative analysis of the impact of explicit incorporation of recency, seasonality and model specialization into fine-grained tourism demand prediction models
Authors: Khatibi Amir , Couto da Silva Ana Paula , Almeida Jussara M. , Gonçalves Marcos A.
Published: December 2022

Forecasting is of utmost importance for the Tourism Industry. The development of models to predict visitation demand to specific places is essential to formulate adequate tourism development plans and policies. Yet, only a handful of models deal with the hard problem of fine-grained (per attraction) tourism demand prediction. In this paper, we argue that three key requirements of this type of application should be fulfilled: (i) recency—forecasting models should consider the impact of recent events (e.g. weather change, epidemics and pandemics); (ii) seasonality—tourism behavior is inherently seasonal; and (iii) model specialization—individual attractions may have very specific idiosyncratic patterns of visitations that should be taken into account. These three key requirements should be considered explicitly and in conjunction to advance the state-of-the-art in tourism prediction models. In our experiments, considering a rich set of indoor and outdoor attractions with environmental and social data, the explicit incorporation of such requirements as features into the models improved the rate of highly accurate predictions by more than 320% when compared to the current state-of-the-art in the field. Moreover, they also help to solve very difficult prediction cases, previously poorly solved by the current models. We also investigate the performance of the models in the (simulated) scenarios in which it is impossible to fulfill all three requirements—for instance, when there is not enough historical data for an attraction to capture seasonality. All in all, the main contributions of this paper are the proposal and evaluation of a new information architecture for fine-grained tourism demand prediction models as well as a quantification of the impact of each of the three aforementioned factors on the accuracy of the learned models. Our results have both theoretical and practical implications towards solving important touristic business demands.
Changing patterns of opioid initiation for pain management in Ontario, Canada: A population-based cross-sectional study
Authors: Gomes Tara , Men Siyu , Campbell Tonya J. , Tadrous Mina , Mamdani Muhammad M. , Paterson J. Michael , Juurlink David N.
Published: December 2022

Introduction

The recent publication of a national guideline and quality standards in Canada have provided clinicians with new, evidence-based recommendations on safe, appropriate opioid use. We sought to characterize how well opioid initiation practices aligned with these recommendations before and following their release.

Methods

We conducted a population-based study among people initiating opioids prior to the release of national guidelines (April 2015—March 2016; fiscal year [FY] 2015) and in the most recent year available (January—December 2019) in Ontario, Canada. We used linked administrative claims data to ascertain the apparent indication for opioid therapy, and characterized the initial daily dose (milligrams morphine or equivalent; MME) and prescription duration for each indication.

Results

In FY2015, 653,885 individuals commenced opioids, compared to 571,652 in 2019. Over time, there were small overall reductions in the prevalence of initial daily doses exceeding 50MME (23.9% vs. 20.1%) and durations exceeding 7 days (17.4% vs. 14.8%); but the magnitude of the reductions varied widely by indication. The prevalence of high dose (>50MME) initial prescriptions reduced significantly across all indications, with the exception of dentist-prescribed opioids (13.6% vs. 12.1% above 50MME). In contrast, there was little change in initial durations exceeding 7 days across most indications, with the exception of some surgical indications (e.g. common excision; 9.3% vs. 6.2%) and among those in palliative care (35.2% vs. 29.2%).

Conclusion

Despite some modest reductions in initiation of high dose and long duration prescription opioids between 2015 and 2019, clinical practice is highly variable, with opioid prescribing practices influenced by clinical indication. These findings may help identify medical specialties well-suited to targeted interventions to promote safer opioid prescribing.
Barriers to reducing preoperative testing for low-risk surgical procedures: A qualitative assessment guided by the Theoretical Domains Framework
Authors: Hall Amanda , Pike Andrea , Patey Andrea , Mortazhejri Sameh , Inwood Samantha , Ruzycki Shannon , Kirkham Kyle , Mahoney Krista , Grimshaw Jeremy
Published: December 2022

Introduction

While numerous guidelines do not recommend preoperative tests for low risk patients undergoing low risk surgeries, they are often routinely performed. Canadian data suggests preoperative tests (e.g. ECGs and chest x-rays) preceded 17.9%-35.5% of low-risk procedures. Translating guidelines into clinical practice can be challenging and it is important to understand what is driving behaviour when developing interventions to change it.

Aim

Thus, we completed a theory-based investigation of the perceived barriers and enablers to reducing unnecessary preoperative tests for low-risk surgical procedures in Newfoundland, Canada.

Method

We used snowball sampling to recruit surgeons, anaesthesiologists, or preoperative clinic nurses. Interviews were conducted by two researchers using an interview guide with 31 questions based on the theoretical domains framework. Data was transcribed and coded into the 14 theoretical domains and then themes were identified for each domain.

Results

We interviewed 17 surgeons, anaesthesiologists, or preoperative clinic nurses with 1 to 34 years’ experience. Overall, while respondents agreed with the guidelines they described several factors, across seven relevant theoretical domains, that influence whether tests are ordered. The most common included uncertainty about who is responsible for test ordering, inability to access patient records or to consult/communicate with colleagues about ordering decisions and worry about surgery delays/cancellation if tests are not ordered. Other factors included workplace norms that conflicted with guidelines and concerns about missing something serious or litigation. In terms of enablers, respondents believed that clear institutional guidelines including who is responsible for test ordering and information about the risk of missing something serious, supported by improved communication between those involved in the ordering process and periodic evaluation will reduce any unnecessary preoperative testing.

Conclusion

These findings suggest that both health system and health provider factors need to be addressed in an intervention to reduce pre-operative testing.
Modularity, balance, and frustration in student social networks: The role of negative relationships in communities
Authors: Brito-Montes José , Canto-Lugo Efrain , Huerta-Quintanilla Rodrigo
Published: December 2022

Signed networks provide information to study the structure and composition of relationships (positive and negative) among individuals in a complex system. Individuals, through different criteria, form groups or organizations called communities. Community structures are one of the important properties of social networks. In this work, we aim to analyze the perturbation of negative relationships in communities. We developed a methodology to obtain and analyze the optimal community partitions in nine school networks in the state of Yucatán, México. We implemented a technique based on the social balance theory in signed networks to complete negative missing links and further applied two methods of community detection: Newman’s and Louvain’s algorithms. We obtain values close to Dunbar’s ratio for both types of relationships, positive and negative. The concepts of balance and frustration were analyzed, and modularity was used to measure the perturbation of negative relationships in communities. We observe differences among communities of different academic degrees. Elementary school communities are unstable, i.e. significantly perturbed by negative relationships, in secondary school communities are semi-stable, and in high school and the university the communities are stable. The analyzes indicate that a greater number of negative links in the networks does not necessarily imply higher instability in the communities, but other social factors are also involved.
Non-enveloped virus membrane penetration: New advances leading to new insights
Authors: Pletan Madison L. , Tsai Billy
Published: December 2022

Host cell membranes pose a particular challenge for non-enveloped viruses. Whereas enveloped viruses enter cells by fusing their lipid envelopes with the cellular membrane, non-enveloped viruses generally must (1) enter cells via endocytosis, then (2) penetrate the cellular endomembrane to reach the cytosol. Only then can the viruses begin to replicate (or transit to the nucleus to replicate). Although membrane penetration of non-enveloped viruses is a crucial entry step, many of the precise molecular details of this process remain unclear. Recent findings have begun to untangle the various mechanisms by which non-enveloped viral proteins disrupt and penetrate cellular endomembranes. Specifically, high-resolution microscopy studies have revealed precise conformational changes in viral proteins that enable penetration, while biochemical studies have identified key host proteins that promote viral penetration and transport. This brief article summarizes new discoveries in the membrane penetration process for three of the most intensely studied families of non-enveloped viruses: reoviruses, papillomaviruses, and polyomaviruses.
SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation
Authors: Liu Yaqing , Katoh Hiroshi , Sekizuka Tsuyoshi , Bae Chaewon , Wakata Aika , Kato Fumihiro , Sakata Masafumi , Yamaji Toshiyuki , Wang Zhiyu , Takeda Makoto
Published: December 2022

Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein–protein interaction networks of the host proteins. From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein.
Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh
Authors: Amin Mohammed Badrul , Talukdar Prabhat Kumar , Asaduzzaman Muhammad , Roy Subarna , Flatgard Brandon M. , Islam Md. Rayhanul , Saha Sumita Rani , Sharker Yushuf , Mahmud Zahid Hayat , Navab-Daneshmand Tala , Kile Molly L. , Levy Karen , Julian Timothy R. , Islam Mohammad Aminul
Published: December 2022

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 μg/L) and low arsenic-contaminated (Matlab, <20 μg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2–7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure.
Bioenergy from forests: Impact of logging residues on the carbon and nitrogen cycles
Authors:   University of Helsinki, Faculty of Agriculture and Forestry, Department of Forest Sciences, Törmänen Tiina
Published: December 2022

Sustainable forest management practices are crucial for minimizing environmental impacts, and to keep forests and the underlying soils healthy to maintain productivity, and to improve adaptability to climate change and mitigate it in the long-term. There, carbon and nitrogen cycling play crucial roles in proper functioning of forest ecosystems. The overall aim of this thesis was to explore the effects of logging residues on the early-stage dynamics of the main nitrogen and carbon cycling processes in upland forest soils after final felling. A specific aim was to compare the effects of logging residue piles consisting of different tree species, i.e., Scots pine (Pinus sylvestris L.), Norway spruce (Picea abies (L.) Karst.), and silver birch (Betula pendula Roth). A special attention was given to the response of soil to different amounts of residues. The effect of logging residues on soil chemical properties and processes was stronger in the organic layer than in the mineral soil layer. Logging residue piles stimulated carbon and nitrogen cycling, especially net nitrification within the first year after the residue treatment. Subsequently, nitrogen was lost via leaching as nitrate and gaseous emission as nitrous oxide. Nitrous oxide fluxes were generally low, although higher in the plots containing logging residues. Spruce residues tended to stimulate nitrous oxide emissions for longer than the residues of the other tree species. Depending on the tree species, nitrous oxide production originated from both autotrophic nitrification and denitrification. Nitrogen concentrations in the soil percolate water already accelerated one year after the establishment of the residue piles. Logging residues increased nitrate and ammonium concentrations, which were highest under birch residues. The effect of logging residue piles on soil was stronger when compared to milder tree species effects. Biological nitrogen fixation activity tended to be higher in branches than in needles or leaves, and higher in coniferous residues. The results of this study raise the importance of more even distribution of logging residues on the forest floor instead of piling them to avoid harmful environmental effects and to maintain soil nutrient balance. The ability of soils to retain nitrogen needs additional attention in forest management practices, especially in boreal areas where nitrogen limits the growth of forests.
Endoscopic and Surgical Management of Blue Rubber Bleb Nevus Syndrome
Authors: Suarez Zoilo K. , Castaneda Daniel , Gonzalez Adalberto , Castro Fernando J. , Erim Tolga
Published: December 2022

Blue rubber bleb nevus syndrome is a rare congenital sporadic disorder characterized by multiple venous malformations localized in the skin, gastrointestinal tract, and internal organs. Gastrointestinal lesions tend to lead to massive or occult bleeding and iron deficiency anemia. The treatment of symptomatic gastrointestinal venous malformations remains a challenge, especially in the setting of recurrent blood loss anemia. An endoscopic approach may be required for refractory cases. We present a case of a 20-year-old patient with blue rubber bleb nevus syndrome with multiple lesions in the stomach, duodenal bulb, small bowel, sigmoid, and descending colon who underwent successful endoscopic mucosal resection, hybrid endoscopic submucosal dissection, and surgical transmural resection of vascular lesions for recurrent bleeding.
Diurnal Fasting During Ramadan Leading to Superior Mesenteric Artery Syndrome
Authors: Ojemolon Pius Ehiremen , Maghari Ibrahim , Almoghrabi Anas
Published: December 2022

Superior mesenteric artery (SMA) syndrome is a favorite of anatomists and clinicians because it results from extrinsic compression of the duodenum by the 2 vascular structures forming the aortomesenteric angle (the descending abdominal aorta and the SMA). Although it is an uncommon cause of upper gastrointestinal obstruction, SMA syndrome can cause significant morbidity. It is more common in younger people. Historically, it has been associated with weight loss and eating disorders, but there are several other risk factors that should be considered in the workup. Cases of SMA syndrome are typically managed conservatively, but surgical referral and intervention may be considered in situations that fail conservative management. We present a case of this rare syndrome in a young man with no medical or psychiatric history during diurnal voluntary fasting in the month of Ramadan.
Geografia “fora” da sala de aula: importância do trabalho de campo para a Geografia Agrária
Authors: Dourado José Aparecido Lima
Published: December 2022

Refletir acerca das questões metodológicas que perpassam o ensino de geografia é fundamental para superar os equívocos que permeiam as práticas pedagógicas nessa disciplina. Não se trata, de um exercício mecânico e sem razão de ser, já que as aulas de geografia têm sido invadidas por um "burocratismo" que emperra a formação de sujeitos capazes de ler e interpretar criticamente o mundo que os cercam. Chama-se à atenção para a forma geralmente descontextualizada com que é trabalhada a disciplina de geografia, fato esse causador de sérios problemas para o processo de ensino e aprendizagem e para a formação de sujeitos capazes de ler criticamente o espaço geográfico. Como proposta metodológica para dinamizar o trabalho nessa área do conhecimento, defende-se a utilização do trabalho de campo, por assim entender que o mesmo possibilita a aproximação entre a teoria e a empiria. Há a preocupação ao longo do texto, em evidenciar a necessidade de adotar alguns critérios para a realização do trabalho de campo, para que o mesmo não seja utilizado para preencher "brechas" decorrentes da falta de um planejamento da disciplina, superando desta forma, compreensões equivocadas que consideram essa atividade apenas como "recreação".