bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Evolution of Duplicated Amylase Gene Regions in Drosophila melanogaster: Evidence of Positive Selection in the Coding Regions and Selective Constraints in the cis-Regulatory Regions
Authors: Araki Hitoshi , Inomata Nobuyuki , Yamazaki Tsuneyuki
Published: April 2021

In this study, we randomly sampled Drosophila melanogaster from Japanese and Kenyan natural populations. We sequenced duplicated (proximal and distal) Amy gene regions to test whether the patterns of polymorphism were consistent with neutral molecular evolution. Fst between the two geographically distant populations, estimated from Amy gene regions, was 0.084, smaller than reported values for other loci, comparing African and Asian populations. Furthermore, little genetic differentiation was found at a microsatellite locus (DROYANETSB) in these samples (Gst′=−0.018). The results of several tests (Tajima's, Fu and Li's, and Wall's tests) were not significantly different from neutrality. However, a significantly higher level of fixed replacement substitutions was detected by a modified McDonald and Kreitman test for both populations. This indicates that positive selection occurred during or immediately after the speciation of D. melanogaster. Sliding-window analysis showed that the proximal region 1, a part of the proximal 5′ flanking region, was conserved between D. melanogaster and its sibling species, D. simulans. An HKA test was significant when the proximal region 1 was compared with the 5′ flanking region of Alcohol dehydrogenase (Adh), indicating a severe selective constraint on the Amy proximal region 1. These results suggest that natural selection has played an important role in the molecular evolution of Amy gene regions in D. melanogaster.
Molecular Identification of virilizer, a Gene Required for the Expression of the Sex-Determining Gene Sex-lethal in Drosophila melanogaster
Authors: Niessen Markus , Schneiter Roger , Nothiger Rolf
Published: April 2021

Sex-lethal (Sxl) is a central switch gene in somatic sexual development of Drosophila melanogaster. Female-specific expression of Sxl relies on autoregulatory splicing of Sxl pre-mRNA by SXL protein. This process requires the function of virilizer (vir). Besides its role in Sxl splicing, vir is essential for male and female viability and is also required for the production of eggs capable of embryonic development. We have identified vir molecularly and found that it produces a single transcript of 6 kb that is ubiquitously expressed in male and female embryos throughout development. This transcript encodes a nuclear protein of 210 kD that cannot be assigned to a known protein family. VIR contains a putative transmembrane domain, a coiled-coil region and PEST sequences. We have characterized five different alleles of vir. Those alleles that affect both sexes are associated with large truncations of the protein, while alleles that affect only the female-specific functions are missense mutations that lie relatively close to each other, possibly defining a region important for the regulation of Sxl.
Mutational Analysis of the Drosophila homothorax Gene
Authors: Kurant Estee , Eytan Dan , Salzberg Adi
Published: April 2021

The homothorax (hth) gene is involved in multiple aspects of embryonic and adult fly development. It encodes a homeodomain-containing protein of the MEIS family and was shown to regulate the subcellular localization of the homeotic protein cofactor Extradenticle (EXD). The HTH protein contains a TALE class homeodomain and a conserved MH domain, which is required for its interaction with EXD. In this work, we describe the structure of the hth locus, characterize at the molecular level a collection of mutant alleles of hth, and discuss the correlation between the identified structural defects and their consequent phenotypes. The hth locus spans more than 100 kb and contains 14 exons. Several of the exon-intron boundaries within the homeodomain and the MH domain-coding regions are conserved between Drosophila and Caenorhabditis elegans. The analysis of hth mutations demonstrates that the homeodomain of HTH is not required for nuclear localization of EXD and that the MH domain-containing first 240 residues are sufficient for nuclear localization of both EXD and HTH. Mutations that alter or delete the homeodomain cause only partial homeotic transformations in the PNS, whereas mutations affecting the MH domain cause distinct and more severe PNS phenotypes. These observations may suggest that driving nuclear localization of EXD is the main role of HTH in patterning the embryonic PNS. They may also suggest that homeodomain-defective HTH protein retains some of its transcription-regulating functions by binding DNA via its interaction with EXD.
Dual-Tagging Gene Trap of Novel Genes inDrosophila melanogaster
Authors: Lukacsovich Tamas , Asztalos Zoltan , Awano Wakae , Baba Kotaro , Kondo Shunzo , Niwa Suguri , Yamamoto Daisuke
Published: April 2021

A gene-trap system is established for Drosophila. Unlike the conventional enhancer-trap system, the gene-trap system allows the recovery only of fly lines whose genes are inactivated by a P-element insertion, i.e., mutants. In the gene-trap system, the reporter gene expression reflects precisely the spatial and temporal expression pattern of the trapped gene. Flies in which gene trap occurred are identified by a two-step screening process using two independent markers, mini-w and Gal4, each indicating the integration of the vector downstream of the promoter of a gene (dual tagging). mini-w has its own promoter but lacks a polyadenylation signal. Therefore, mini-w mRNA is transcribed from its own promoter regardless of the vector integration site in the genome. However, the eyes of flies are not orange or red unless the vector is incorporated into a gene enabling mini-w to be spliced to a downstream exon of the host gene and polyadenylated at the 3′ end. The promoter-less Gal4 reporter is expressed as a fusion mRNA only when it is integrated downstream of the promoter of a host gene. The exons of trapped genes can be readily cloned by vectorette RT-PCR, followed by RACE and PCR using cDNA libraries. Thus, the dual-tagging gene-trap system provides a means for (i) efficient mutagenesis, (ii) unequivocal identification of genes responsible for mutant phenotypes, (iii) precise detection of expression patterns of trapped genes, and (iv) rapid cloning of trapped genes.
Comparative Analysis of the nonA Region in Drosophila Identifies a Highly Diverged 5′ Gene That May Constrain nonA Promoter Evolution
Authors: Campesan Susanna , Chalmers David , Sandrelli Federica , Megighian Aram , Peixoto Alexandre A , Costa Rodolfo , Kyriacou Charalambos P
Published: April 2021

A genomic fragment from Drosophila virilis that contained all the no-on-transientA (nonA) coding information, plus several kilobases of upstream material, was identified. Comparisons of nonA sequences and the gene nonA-like in D. melanogaster, a processed duplication of nonA, suggest that it arose before the split between D. melanogaster and D. virilis. In both species, another gene that lies <350 bp upstream from the nonA transcription starts, and that probably corresponds to the lethal gene l(1)i19, was identified. This gene encodes a protein that shows similarities to GPI1, which is required for the biosynthesis of glycosylphosphatidylinositol (GPI), a component for anchoring eukaryotic proteins to membranes, and so we have named it dGpi1. The molecular evolution of nonA and dGpi1 sequences show remarkable differences, with the latter revealing a level of amino acid divergence that is as high as that of transformer and with extremely low levels of codon bias. Nevertheless, in D. melanogaster hosts, the D. virilis fragment rescues the lethality associated with a mutation of l(1)i19e, as well as the viability and visual defects produced by deletion of nonA–. The presence of dGpi1 sequences so close to nonA appears to have constrained the evolution of the nonA promoter.
Recombination and Spontaneous Mutation at the Major Cluster of Resistance Genes in Lettuce (Lactuca sativa)
Authors: Chin Doris B , Arroyo-Garcia Rosa , Ochoa Oswaldo E , Kesseli Rick V , Lavelle Dean O , Michelmore Richard W
Published: April 2021

Two sets of overlapping experiments were conducted to examine recombination and spontaneous mutation events within clusters of resistance genes in lettuce. Multiple generations were screened for recombinants using PCR-based markers flanking Dm3. The Dm3 region is not highly recombinagenic, exhibiting a recombination frequency 18-fold lower than the genome average. Recombinants were identified only rarely within the cluster of Dm3 homologs and no crossovers within genes were detected. Three populations were screened for spontaneous mutations in downy mildew resistance. Sixteen Dm mutants were identified corresponding to spontaneous mutation rates of 10–3 to 10–4 per generation for Dm1, Dm3, and Dm7. All mutants carried single locus, recessive mutations at the corresponding Dm locus. Eleven of the 12 Dm3 mutations were associated with large chromosome deletions. When recombination could be analyzed, deletion events were associated with exchange of flanking markers, consistent with unequal crossing over; however, although the number of Dm3 paralogs was changed, no novel chimeric genes were detected. One mutant was the result of a gene conversion event between Dm3 and a closely related homolog, generating a novel chimeric gene. In two families, spontaneous deletions were correlated with elevated levels of recombination. Therefore, the short-term evolution of the major cluster of resistance genes in lettuce involves several genetic mechanisms including unequal crossing over and gene conversion.
Population Admixture: Detection by Hardy-Weinberg Test and Its Quantitative Effects on Linkage-Disequilibrium Methods for Localizing Genes Underlying Complex Traits
Authors: Deng Hong-Wen , Chen Wei-Min , Recker Robert R
Published: April 2021

In association studies searching for genes underlying complex traits, the results are often inconsistent, and population admixture has been recognized qualitatively as one major potential cause. Hardy-Weinberg equilibrium (HWE) is often employed to test for population admixture; however, its power is generally unknown. Through analytical and simulation approaches, we quantify the power of the HWE test for population admixture and the effects of population admixture on increasing the type I error rate of association studies under various scenarios of population differentiation and admixture. We found that (1) the power of the HWE test for detecting population admixture is usually small; (2) population admixture seriously elevates type I error rate for detecting genes underlying complex traits, the extent of which depends on the degrees of population differentiation and admixture; (3) HWE testing for population admixture should be performed with random samples or only with controls at the candidate genes, or the test can be performed for combined samples of cases and controls at marker loci that are not linked to the disease; (4) testing HWE for population admixture generally reduces false positive association findings of genes underlying complex traits but the effect is small; and (5) with population admixture, a linkage disequilibrium method that employs cases only is more robust and yields many fewer false positive findings than conventional case-control analyses. Therefore, unless random samples are carefully selected from one homogeneous population, admixture is always a legitimate concern for positive findings in association studies except for the analyses that deliberately control population admixture.
Effects of pore water distributions on P-wave velocity–water saturation relations in partially saturated sandstones
Authors: Horikawa T , Katsura M , Yokota T , Nakashima S
Published: April 2021

We have developed a new method for introducing the effects of pore water distribution into the interpretation of P-wave velocity (VP) dispersion in a partially saturated rock. Pore water in an unsaturated rock is distributed as patches, and mesoscopic-scale wave-induced fluid flow (WIFF) from saturated patches to empty patches is known as a key mechanism for interpreting P-wave dispersion. Mesoscopic WIFF depends on permeability and the scale of the saturated patch, thus evaluating their influences is important for estimating the relationship between water saturation (${S_{\rm{w}}}$) and VP. The simplest and conventional law for simulating the ${S_{\rm{w}}} - {V_{{P}}}$ relation considering the mesoscopic WIFF is White's model, which describes the patch size changes proportional to the saturation. However, White's model assumes homogeneity in the size and distribution of pores, and does not consider the effects of pore water distribution in a partially saturated rock. In the rock, pore water is distributed heterogeneously according to the pore radius, causing non-linear changes in the permeability and size of the saturated patches against the water saturation. In this study, we modified White's model by introducing relative permeability and a new coefficient describing the nonlinear change of the patch size into the conventional version, and applied the modified model to better interpret our experimental ${S_{\rm{w}}} - {V_{{P}}}$ relations, which were measured by an ultrasonic technique at 200 and 500 kHz for two types of Berea sandstone samples with different permeabilities as their water saturation was decreased by evaporative drying. The relative permeabilities were determined by applying the Mualem–van Genuchten model into the capillary pressure curves from mercury intrusion porosimetry. Furthermore, we proposed a calculation method for the new coefficient using tortuosity, which corresponds to the pore water connection. The modified White's model could reproduce the experimental ${S_{\rm{w}}} - {V_{{P}}}$ relations better than other conventional models. Consequently, our modification, considering the effect of pore water distribution, would be useful for more quantitative interpretation of P-wave velocity and attenuation under coexisting multifluid conditions.
Two-dimensional meshless modelling and TE-mode inversion of magnetotelluric data
Authors: Wittke J , Tezkan B
Published: April 2021

We present a new 2-D forward modelling and inversion scheme to interpret magnetotelluric/radio-magnetotelluric data by utilizing a novel meshless forward operator. We use this discretization technique within an inverse scheme to recover conductivity structures from given magnetotelluric data. To approximate solutions of the partial differential equations that describe the magnetotelluric experiment, we discretize the subsurface only in terms of nodes. These node sets, which are simple to generate, are used to derive the differential operators’ approximations in a generalized meshless framework. First, we study and compare forward modelling calculations to an analytical and known solution from the literature. Several example calculations are given, which validate the proposed meshless forward operator. We then formulate our inverse scheme for TE-mode data, which uses only subsets of the nodal subsurface parametrization to generate conductivity structures from this given data. The inverse scheme consists of a Gauss–Newton algorithm combined with the generalized meshless framework. To validate the algorithm, we present inversion results from synthetic and field data. We compare our results to conductivity models calculated by established, well-known inversion schemes and literature results. We report that our algorithm can accurately model magnetotelluric responses and recover meaningful conductivity models, explaining given magnetotelluric data.
Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1
Authors: Jia Wenjuan , Zou Xia , Xu Zhijue , Bai Lin , Shan Aidong , Li Yankun , Shi Jingjing , Yang Fang , Ding Chen , Narimatsu Hisashi , Zhang Yan
Published: April 2021

Mucin-type O-glycosylation is initiated by the polypeptide: N-acetylgalactosaminyltransferase (ppGalNAc-T) family of enzymes, which consists of 20 members in humans. Among them, unlike other ppGalNAc-Ts located in Golgi apparatus, ppGalNAc-T18 distributes primarily in the endoplasmic reticulum (ER) and non-catalytically regulates ER homeostasis and O-glycosylation. Here, we report the mechanism for ppGalNAc-T18 ER localization and the function of each structural domain of ppGalNAc-T18. By using ppGalNAc-T18 truncation mutants, we revealed that the luminal stem region and catalytic domain of ppGalNAc-T18 are essential for ER localization, whereas the lectin domain and N-glycosylation of ppGalNAc-T18 are not required. In the absence of the luminal region (i.e., stem region, catalytic and lectin domains), the conserved Golgi retention motif RKTK within the cytoplasmic tail combined with the transmembrane domain ensure ER export and Golgi retention, as observed for other Golgi resident ppGalNAc-Ts. Results from coimmunoprecipitation assays showed that the luminal region interacts with ER resident proteins UGGT1, PLOD3 and LPCAT1. Furthermore, flow cytometry analysis showed that the entire luminal region is required for the non-catalytic O-GalNAc glycosylation activity of ppGalNAc-T18. The findings reveal a novel subcellular localization mechanism of ppGalNAc-Ts and provide a foundation to further characterize the function of ppGalNAc-T18 in the ER.
The role of cell surface sialic acids for SARS-CoV-2 infection
Authors: Sun Xue-Long
Published: April 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new virus that has higher contagious capacity than any other previous human coronaviruses (HCoVs) and causes the current coronavirus disease 2019 pandemic. Sialic acids are a group of nine-carbon acidic α-keto sugars, usually located at the end of glycans of cell surface glycoconjugates and serve as attachment sites for previous HCoVs. It is therefore speculated that sialic acids on the host cell surface could serve as co-receptors or attachment factors for SARS-CoV-2 cell entry as well. Recent in silico modeling, molecular modeling predictions and microscopy studies indicate potential sialic acid binding by SARS-CoV-2 upon cell entry. In particular, a flat sialic acid-binding domain was proposed at the N-terminal domain of the spike protein, which may lead to the initial contact and interaction of the virus on the epithelium followed by higher affinity binding to angiotensin-converting enzyme 2 (ACE2) receptor, likely a two-step attachment fashion. However, recent in vitro and ex vivo studies of sialic acids on ACE2 receptor confirmed an opposite role for SARS-CoV-2 binding. In particular, neuraminidase treatment of epithelial cells and ACE2-expressing 293T cells increased SARS-CoV-2 binding. Furthermore, the ACE2 glycosylation inhibition studies indicate that sialic acids on ACE2 receptor prevent ACE2–spike protein interaction. On the other hand, a most recent study indicates that gangliosides could serve as ligands for receptor-binding domain of SARS-CoV-2 spike protein. This mini-review discusses what has been predicted and known so far about the role of sialic acid for SARS-CoV-2 infection and future research perspective.
Genetic diversity of the Sudanese: insights on origin and implications for health
Authors: Ibrahim Muntaser E
Published: April 2021

By virtue of their cultural, linguistic and genetic legacies, many populations from Sudan have deep histories in the region and retain high genetic diversities. Sudan’s location in north east Africa, a unique spot believed to act as a climatic refuge during periods of climate extremes, might have dictated that fate. Among the marked consequences of this diversity is the potential to provide information on the origin and structure of human populations within and outside the continent, as well as migration patterns towards various parts of the African continent, and out of Africa. The diverse Sudanese gene pool further has the potential to inform on genetic adaptations driven by culture and the environment resulting in unique and interesting traits, some of which are yet to be investigated. In addition, these genomes could offer clues to complex issues of causation amidst the challenge of new paradigms in biology underpinned by the genomic revolution.
Long-term viability and extensibility of an in situ regenerated canine aortic wall using hybrid warp-knitted fabric
Authors: Nemoto Shintaro , Konishi Hayato , Suzuki Tatsuya , Shimada Ryo , Katsumata Takahiro , Osawa Satomi , Yamaguchi Ayuko
Published: April 2021

OBJECTIVES

Many surgical materials promoting tissue regeneration have been explored for use in paediatric cardiac surgery. The aim of this study is to evaluate the long-term viability and extensibility of the canine aortic wall regenerated using a novel synthetic hybrid fabric.

METHODS

The sheet is a warp-knitted fabric of biodegradable (poly-l-lactic acid) and non-biodegradable (polyethylene terephthalate) yarns coated with cross-linked gelatine. This material was implanted as a patch to fill an oval-shaped defect created in the canine descending aorta. The tissue samples were explanted after 12, 24 or 36 months (N = 3, 2, 2, respectively) for histological examination and biomechanical testing.

RESULTS

There was no shrinkage, rupture or aneurysmal change after 24 months. The regenerated wall showed prototypical vascular healing without material degeneration, chronic inflammation, calcification or abnormal intimal overgrowth. Bridging tissue across the patch was well-formed and had expanded over time. The biodegradable yarns had completely degraded at 24 months after implantation, as scheduled, but the regenerated aortic wall demonstrated satisfactory levels of mechanical strength and extensibility in tensile strength tests.

CONCLUSIONS

The sheet achieved good long-term viability and extensibility in the regenerated aortic wall. These findings suggest that it is a promising surgical material for repairing congenital heart defects. Further developments of the sheet are required, including clinical studies.
How advanced is the epidemiological transition in Papua New Guinea? New evidence from verbal autopsy
Authors: Hart John D , Kwa Viola , Dakulala Paison , Ripa Paulus , Frank Dale , Golpak Victor , Adair Timothy , Mclaughlin Deirdre , Riley Ian D , Lopez Alan D
Published: April 2021

Background

Reliable cause of death (COD) data are not available for the majority of deaths in Papua New Guinea (PNG), despite their critical policy value. Automated verbal autopsy (VA) methods, involving an interview and automated analysis to diagnose causes of community deaths, have recently been trialled in PNG. Here, we report VA results from three sites and highlight the utility of these methods to generate information about the leading CODs in the country.

Methods

VA methods were introduced in one district in each of three provinces: Alotau in Milne Bay; Tambul-Nebilyer in Western Highlands; and Talasea in West New Britain. VA interviews were conducted using the Population Health Metrics Research Consortium (PHMRC) shortened questionnaire and analysed using the SmartVA automated diagnostic algorithm.

Results

A total of 1655 VAs were collected between June 2018 and November 2019, 87.0% of which related to deaths at age 12 years and over. Our findings suggest a continuing high proportion of deaths due to infectious diseases (27.0%) and a lower proportion of deaths due to non-communicable diseases (NCDs) (50.8%) than estimated by the Global Burden of Disease Study (GBD) 2017: 16.5% infectious diseases and 70.5% NCDs. The proportion of injury deaths was also high compared with GBD: 22.5% versus 13.0%.

Conclusions

Health policy in PNG needs to address a ‘triple burden’ of high infectious mortality, rising NCDs and a high fraction of deaths due to injuries. This study demonstrates the potential of automated VA methods to generate timely, reliable and policy-relevant data on COD patterns in hard-to-reach populations in PNG.
Syndromic surveillance using monthly aggregate health systems information data: methods with application to COVID-19 in Liberia
Authors: Fulcher Isabel R , Boley Emma Jean , Gopaluni Anuraag , Varney Prince F , Barnhart Dale A , Kulikowski Nichole , Mugunga Jean-Claude , Murray Megan , Law Michael R , Hedt-Gauthier Bethany ,   the Cross-site COVID-19 Syndromic Surveillance Working Group
Published: April 2021

Background

Early detection of SARS-CoV-2 circulation is imperative to inform local public health response. However, it has been hindered by limited access to SARS-CoV-2 diagnostic tests and testing infrastructure. In regions with limited testing capacity, routinely collected health data might be leveraged to identify geographical locales experiencing higher than expected rates of COVID-19-associated symptoms for more specific testing activities.

Methods

We developed syndromic surveillance tools to analyse aggregated health facility data on COVID-19-related indicators in seven low- and middle-income countries (LMICs), including Liberia. We used time series models to estimate the expected monthly counts and 95% prediction intervals based on 4 years of previous data. Here, we detail and provide resources for our data preparation procedures, modelling approach and data visualisation tools with application to Liberia.

Results

To demonstrate the utility of these methods, we present syndromic surveillance results for acute respiratory infections (ARI) at health facilities in Liberia during the initial months of the COVID-19 pandemic (January through August 2020). For each month, we estimated the deviation between the expected and observed number of ARI cases for 325 health facilities and 15 counties to identify potential areas of SARS-CoV-2 circulation.

Conclusions

Syndromic surveillance can be used to monitor health facility catchment areas for spikes in specific symptoms which may indicate SARS-CoV-2 circulation. The developed methods coupled with the existing infrastructure for routine health data systems can be leveraged to monitor a variety of indicators and other infectious diseases with epidemic potential.
Experiences and perceptions of foreign-language customers on medication information received in the pharmacy – a focus group study
Authors: Sletvold Hege , Nguyen Thianna
Published: April 2021

Background

In pharmacies, communication is essential for providing information about medicine and counselling customers on the correct use of medications. Previous studies have described pharmacists experiencing language and cultural barriers in communication with foreign-language (FL) customers.

Objective

This study aimed to explore FL customer experiences and perceptions of medication information received in the pharmacy.

Methods

A qualitative method was used, including interviews in five focus groups. Study participants (N = 18) spoke Arabic or Kurdish but lived in Norway and had the experience of purchasing medicine over the counter and/or prescription medicines in a Norwegian pharmacy. A descriptive thematic content analysis was conducted.

Key findings

Overall, the FL customers were satisfied with the pharmacy service. However, they were divided in their views of the pharmacy role, which could affect how they received medication information. Communication barriers were prominent, and FL customers related language and cultural barriers to negative health outcomes. Their preferences on medication information were not met. Several communication facilitators that could support medication information were mentioned: simplified prescription labels, written information, pictograms, mobile apps, interpretators and bilingual staff.

Conclusions

The FL pharmacy customers’ experience of communication barriers and unfulfilled needs for medical information can be a threat to patient safety. To overcome the barriers and ensure the correct use of medicines, health-care personnel in pharmacies must apply an array of communication aids, adapted to the diversity in language, culture and health literacy in the heterogenous population.
Low back pain management – What Australian community pharmacists recommend and how this compares to current clinical guidelines
Authors: Mishriky John , Stupans Ieva , Chan Vincent
Published: April 2021

Background

Low back pain (LBP) is a serious and debilitating condition that necessitates proper assessment and management. Community pharmacists are ideally positioned to interact with these patients and provide therapeutic recommendations in line with LBP clinical guidelines, which have changed in recent years. Understanding what therapeutic strategies pharmacists recommend and why, can provide insights into whether these recommendations are in line with current clinical resources.

Objectives

The objectives of this study were to examine community pharmacists’ views, knowledge and practices in LBP management compared to current clinical guidelines; and investigate their views regarding the accessibility and use of clinical LBP resources.

Methods

A cross-sectional study of Australian community pharmacists was conducted using a structured, self-administered, anonymous online survey. Primary outcomes assessed were pharmacists’ views, practices and recommendations in low back pain of different severities, as well as views on the use and accessibility of clinical guidelines.

Key findings

A total of 176 pharmacists completed the survey. Most recommended non-pharmacological strategies to manage mild symptoms for both adult and teenage groups, escalating to pharmacological with increasing symptom severity. Approximately 75% reported they would recommend ibuprofen over paracetamol for low back pain. Approximately 40% agreed there is difficulty in finding and accessing clinical resources and more than 40% reported being unaware that there are specific guidelines available for the management of LBP symptoms.

Conclusion

Results from this study highlight an important need to further improve the knowledge and awareness of pharmacists in low back pain management, including locating and accessing clinical resources.
Analysis of the optimal time to withdraw investments from hedge funds with alternative fee structures
Authors: Meng Fei , Saunders David
Published: April 2021

We study the optimal stopping problem arising from an investor determining the best time to withdraw from a hedge fund with a shared loss fee structure and a positive fee for assets under management—a decision that is critically important to the viability of such products in practice. The optimal solution is characterized as the first exit time of the fund value from a bounded region with upper and lower stopping boundaries. In the infinite horizon case, we present the complete solution to the optimal stopping problem, while in the finite horizon case we derive a pair of coupled integral equations for the stopping bounds and present an asymptotic analysis of the stopping boundaries for small time. The analysis requires new mathematical results extending techniques suitable for options with one exercise boundary to the case of a coupled pair of upper and lower boundaries.
Convergence and rate optimality of adaptive multilevel stochastic Galerkin FEM
Authors: Bespalov Alex , Praetorius Dirk , Ruggeri Michele
Published: April 2021

We analyze an adaptive algorithm for the numerical solution of parametric elliptic partial differential equations in two-dimensional physical domains, with coefficients and right-hand-side functions depending on infinitely many (stochastic) parameters. The algorithm generates multilevel stochastic Galerkin approximations; these are represented in terms of a sparse generalized polynomial chaos expansion with coefficients residing in finite element spaces associated with different locally refined meshes. Adaptivity is driven by a two-level a posteriori error estimator and employs a Dörfler-type marking on the joint set of spatial and parametric error indicators. We show that, under an appropriate saturation assumption, the proposed adaptive strategy yields optimal convergence rates with respect to the overall dimension of the underlying multilevel approximation spaces.
Decreased Use of Broad-Spectrum Antibiotics During the Coronavirus Disease 2019 Epidemic in South Korea
Authors: Ryu Sukhyun , Hwang Youngsik , Ali Sheikh Taslim , Kim Dong-Sook , Klein Eili Y , Lau Eric H Y , Cowling Benjamin J
Published: April 2021

Background

Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a concern over possible increase in antibiotic use due to coinfections among COVID-19 patients in the community. Here, we evaluate the changes in nationwide use of broad-spectrum antibiotics during the COVID-19 epidemic in South Korea.

Methods

We obtained national reimbursement data on the prescription of antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, fluoroquinolones, and macrolides. We examined the number of antibiotic prescriptions compared with the previous 3 years in the same period from August to July. To quantify the impact of the COVID-19 epidemic on antibiotic use, we developed a regression model adjusting for changes of viral acute respiratory tract infections (ARTIs), which are an important factor driving antibiotic use.

Results

During the COVID-19 epidemic in South Korea, the broad-spectrum antibiotic use dropped by 15%–55% compared to the previous 3 years. Overall reduction in antibiotic use adjusting for ARTIs was estimated to be 14%–30%, with a larger impact in children.

Conclusions

Our study found that broad-spectrum antibiotic use was substantially reduced during the COVID-19 epidemic in South Korea. This reduction can be in part due to reduced ARTIs as a result of stringent public health interventions including social distancing measures.
Restoring neuro-immune circuitry after brain and spinal cord injuries
Authors: Ueno Masaki
Published: April 2021

Neuro-immune interactions are essential for our body’s defense and homeostasis. Anatomical and physiological analyses have shown that the nervous system comprises multiple pathways that regulate the dynamics and functions of immune cells, which are mainly mediated by the autonomic nervous system and adrenal signals. These are disturbed when the neurons and circuits are damaged by diseases of the central nervous system (CNS). Injuries caused by stroke or trauma often cause immune dysfunction by abrogation of the immune-regulating neural pathways, which leads to an increased risk of infections. Here, I review the structures and functions of the neural pathways connecting the brain and the immune system, and the neurogenic mechanisms of immune dysfunction that emerge after CNS injuries. Recent technological advances in manipulating specific neural circuits have added mechanistic aspects of neuro-immune interactions and their dysfunctions. Understanding the neural bases of immune control and their pathological processes will deepen our knowledge of homeostasis and lead to the development of strategies to cure immune deficiencies observed in various CNS disorders.
Pet husbandry as a risk factor for colonization or infection with MDR organisms: a systematic meta-analysis
Authors: Hackmann Carolin , Gastmeier Petra , Schwarz Stefan , Lübke-Becker Antina , Bischoff Peter , Leistner Rasmus
Published: April 2021

Background

MDR organisms (MDROs) pose a relevant risk for patients in modern healthcare. Although ownership of pet animals is common and owners and pets commonly live in close contact, it is still unclear whether pet ownership may be considered as a risk factor for MDRO acquisition prior to hospitalization.

Methods

We performed three separate meta-analyses in accordance with the PRISMA guidelines, assessing contact to pets as a risk factor for acquisition of MRSA, VRE and MDR Gram-negatives [namely third-generation cephalosporin-resistant Enterobacterales (3GCRE) and carbapenem-resistant Enterobacterales (CRE)].

Results

We calculated an increased risk of MRSA carriage for dog owners [risk ratio (RR) 2.28, 95% CI 1.47–3.56]. Meta-analysis did not show a significantly higher risk for 3GCRE colonization among owners of different pet species compared with non-pet owners (RR 1.18, 95% CI 0.83–1.68 for pet owners in general, RR 0.88, 95% CI 0.56–1.40 for dog owners, RR 1.16, 95% CI 0.58–2.34 for cat owners, RR 1.34, 95% CI 0.43–4.18 for rodent owners, RR 0.91, 95% CI 0.38–2.18 for bird owners, and RR 2.34, 95% CI 0.33–16.63 for lizard/frog owners). For VRE, there were insufficient data to perform a meta-analysis.

Conclusions

Our analyses suggest contact to pet animals is a risk factor for MRSA, but not for 3GCRE/CRE acquisition. Evaluation of the underlying literature suggested a possible role of pet animals as: (i) vectors for the transmission of MDROs between livestock and humans; as well as (ii) a reservoir for MDROs. Pets, therefore, may promote transmission and reinfection of humans.
Influence of amount and frequency of protein supplementation to steers consuming low-quality, cool-season forage: intake, nutrient digestibility, and ruminal fermentation
Authors: Cappellozza Bruno I , Bohnert David W , Reis Maria M , Swanson Kendall C , Falck Stephanie J , Cooke Reinaldo F
Published: April 2021

This experiment evaluated the influence of protein supplementation frequency (SF) and amount offered on intake, nutrient digestibility, and ruminal fermentation by rumen-fistulated beef steers consuming low-quality [2.9% crude protein (CP); dry matter (DM) basis], cool-season forage. Seven Angus × Hereford steers (300 ± 27 kg) fitted with ruminal cannulas were randomly assigned to 1 of 7 treatments in an incomplete 7 × 4 Latin square. Treatments, in a 2 × 3 factorial design plus a non-supplemented control (CON), consisted of 2 levels of supplemental soybean meal, 100% (F) or 50% (H) of the estimated rumen-degradable protein requirement, provided daily (D), once every 5 d (5D), or once every 10 d (10D). Experimental periods were 30 d and dry matter intake (DMI) was measured from days 19 to 28. On days 21 (all supplements provided) and 30 (only daily supplements provided; day immediately prior to supplementation for 5D and 10D treatments) ruminal fluid was collected for ruminal pH, ammonia-N (NH3), volatile fatty acids (VFA), and determination of ruminal fermentation variables. Forage and total DM, organic matter (OM), and nitrogen (N) intake increased with supplementation (P ≤ 0.04). However, a linear effect of SF × amount of supplement interaction was observed for forage and total DM, OM, and N intake (P ≤ 0.04), with each variable decreasing as SF decreased, but the decrease being greater with F vs. H. Apparent total tract DM, OM, and neutral detergent fiber digestibility was not affected by supplementation or amount of supplement provided (P ≥ 0.10). In contrast, N digestibility increased with supplementation and for F vs. H (P < 0.01). Digestibility of DM, OM, and N increased linearly as SF decreased (P ≤ 0.03). When all supplements were provided, ruminal NH3, total VFA, and molar proportions of all individual VFA increased with supplementation (P ≤ 0.04), whereas acetate:propionate ratio decreased (P < 0.01). When only daily supplements were provided, none of the aforementioned fermentation parameters were affected (P ≥ 0.09). In summary, reducing the amount of supplemental CP provided to ruminants consuming low-quality forages, when supplementation intervals are >5 d, can be a management tool to maintain acceptable levels of DMI, nutrient digestibility, and ruminal fermentation while reducing supplementation cost.
LINC01207 is up-regulated in gastric cancer tissues and promotes disease progression by regulating miR-671-5p/DDX5 axis
Authors: Liu Hongquan , Liu Xiaoyu
Published: April 2021

LINC01207 is involved in the progression of some cancers. This study was designed to delve into the biological function and mechanism of LINC01207 in gastric cancer. Quantitative polymerase chain reaction (qPCR) was adopted to examine the expression levels of LINC01207, miR-671-5p, dead-box polypeptide 5 (DDX5) mRNA in gastric cancer tissues and cells. After LINC01207 was overexpressed or depleted, MTT and bromodeoxyuridine (BrdU) assays were conducted to detect cell proliferation. Transwell assay was employed to detect cell migration and invasion. Western blot was used to detect the expression of DDX5 protein in cells. Bioinformatics analysis, luciferase reporter assay and RNA pull-down assay were performed to predict and validate the binding site between miR-671-5p and LINC01207 or DDX5. LINC01207 and DDX5 mRNA were upregulated in gastric cancer, while miR-671-5p was downregulated; high expression of LINC01207 and transfection of miR-671-5p inhibitors facilitated the proliferation of gastric cancer cells; however, knocking down LINC01207 and the overexpression of miR-671-5p mimics had opposite biological effects. LINC01207 and miR-671-5p were interacted and miR-671-5p was negatively regulated by LINC01207. MiR-671-5p could reverse the function of LINC01207. DDX5 was a downstream target of miR-671-5p and was positively modulated by LINC01207. LINC01207 promotes the proliferation and metastasis of gastric cancer cells by regulating miR-671-5p/DDX5 axis.
SRPS–deep-learning-based photometric stereo using superresolution images
Authors: Song Euijeong , Kim Seokjung , Chung Seok , Chang Minho
Published: April 2021

This paper introduces a novel deep-learning-based photometric stereo method that uses superresolution (SR) images: SR photometric stereo. Recent deep-learning-based SR algorithms have yielded great results in terms of enlarging images without mosaic effects. Supposing that the SR algorithms successfully enhance the feature and colour information of original images, implementing SR images using the photometric stereo method facilitates the use of considerably more information on the object than existing photometric stereo methods. We built a novel deep-learning-based network for the photometric stereo technique to optimize the input–output of SR image inputs and normal map outputs. We tested our network using the most widely used benchmark dataset and obtained better results than existing photometric stereo methods.
Uncomfortably Numb: The Disconnect between Individual Human Rights Perceptions and State Human Rights Practices
Authors: Yates Tyler P
Published: April 2021

In this article I argue the average person does not have an accurate perception of their government’s human rights practices. Individuals are unable to accurately gauge their government’s human rights behaviours due to a conflation of indifference, personal biases, and focused reframing efforts by the government and other interested parties. This disconnect between state practice and individual perception creates an informational barrier for human rights activists and non-governmental organizations that threatens both their public support and their ability to meet objectives. I offer analysis of the above arguments by examining a survey question from the World Values Study that asks participants to rank their state’s human rights behaviour. I find that there is no direct correlation between these perceived rankings and the state s actual human rights practices. Further, I find that individuals living in states with higher existing levels of personal human rights are more likely to have a negative view of their state’s human rights performance. Finally, I find that individuals from states with a history of past political violence are more likely to demonstrate inflated perceptions of their state’s human rights practices. These findings elucidate the necessity for human rights organizations to take account of, and potentially combat, the disconnect between individuals’ human rights perceptions and states’ action when engaging in activism.
Using 2D dental geometric morphometrics to identify modernPerognathusandChaetodipusspecimens (Rodentia, Heteromyidae)
Authors: Wyatt Megan R , Hopkins Samantha S B , Davis Edward B
Published: April 2021

The Heteromyidae (pocket mice and kangaroo rats) are a group of extant small rodents abundant in western North America, as well as in fossil assemblages over the last 20 million years. Two genera of heteromyids, Chaetodipus and Perognathus, share similar tooth morphology and teeth are the primary fossil remains. Previous genetic studies show these extant sister genera likely diverged in the middle Miocene (~16 million years ago); however, the Chaetodipus fossil record starts in the Pleistocene (~2 million years ago). In this study, we asked whether two-dimensional geometric morphometrics on complete dentition and isolated premolars can accurately identify Chaetodipus and Perognathus specimens at the genus and species level. We landmarked the occlusal surface of the upper and lower tooth rows of modern Chaetodipus (n = 83) and Perognathus specimens (n = 80), including 12 of the 26 extant species across the two genera. We ran a canonical variates analysis to investigate whether principal component variation could predict known taxonomic identifications. The morphospace using complete dentition can identify specimens to genus with 90 – 92% accuracy and to species with more variable accuracy. We found an isolated premolar provides sufficient information for genus-level identification (69 – 84% accuracy), but not for species-level identification (26 – 56% accuracy). This morphospace of modern specimens can be used to identify the skeletal remains of Chaetodipus and Perognathus in museum collections, raptor pellets, or middens, to refine our existing knowledge of heteromyid evolutionary history.
Nonprofits: A Public Policy Tool for the Promotion of Community Subjective Well-being
Authors: Ressler Robert W , Paxton Pamela , Velasco Kristopher , Pivnick Lilla , Weiss Inbar , Eichstaedt Johannes C
Published: April 2021

Looking to supplement common economic indicators, politicians and policymakers are increasingly interested in how to measure and improve the subjective well-being of communities. Theories about nonprofit organizations suggest that they represent a potential policy-amenable lever to increase community subjective well-being. Using longitudinal cross-lagged panel models with IRS and Twitter data, this study explores whether communities with higher numbers of nonprofits per capita exhibit greater subjective well-being in the form of more expressions of positive emotion, engagement, and relationships. We find associations, robust to sample bias concerns, between most types of nonprofit organizations and decreases in negative emotions, negative sentiments about relationships, and disengagement. We also find an association between nonprofit presence and the proportion of words tweeted in a county that indicate engagement. These findings contribute to our theoretical understanding of why nonprofit organizations matter for community-level outcomes and how they should be considered an important public policy lever.
Glucosamine attenuates drug resistance in Mitoxantrone-resistance breast cancer cells
Authors: Valinezhad Sani Fatemeh , Palizban Abbasali , Mosaffa Fatemeh , Jamialahmadi Khadijeh
Published: April 2021

Objectives

This study was aimed at investigating the cytotoxicity and multi-drug resistance (MDR) reversal effect of Glucosamine (GlcN) on resistant BCRP-overexpressing breast cancer MCF-7/MX cells.

Methods

After confirming the overexpression of BCRP, the cytotoxicity and MDR reversing potential of GlcN on MCF-7/MX mitoxantrone-resistant and MCF-7 sensitive breast cancer cells were assessed via MTT assay. The effects of GlcN on mitoxantrone accumulation were analyzed through flow cytometry. Finally, the expression of BCRP and Epithelial-Mesenchymal Transition (EMT)-related markers following the exposure to GlcN were assessed by real-time RT-PCR.

Key findings

This study showed that glucosamine had an inhibitory effect on the proliferation of human breast cancer cells. The respective IC50 values for MCF-7/MX cells following exposure to mitoxantrone (MX) in the presence of GlcN (0, 0.5 and 1 mm) for 72 h were 3.61 ± 0.21, 0.598 ± 0.041 and 0.284 ± 0.016 μm, respectively. Furthermore, GlcN reduced the expression of BCRP mRNA without any significant effect on EMT-related markers in breast cancer cells.

Conclusions

These results proposed that glucosamine as a natural sugar could down regulate the BCRP expression and increased MX cytotoxicity in breast cancer cells.