bluuebunny/crossref_metadata_2025 huggingface dataset:
Personal protection with PBO-pyrethroid synergist-treated nets after 2 years of household use against pyrethroid-resistant Anopheles in Tanzania
Authors: Martin Jackline L. , Mosha Franklin W. , Lukole Eliud , Rowland Mark , Todd Jim , Charlwood Jacques D. , Mosha Jacklin F. , Protopopoff Natacha
Published: March 2021

Background

The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use.

Methods

From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays.

Results

Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01–0.13, p < 0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories, but more were collected inside the more damaged nets (HI ≥ 643) than in less damaged (HI 0–64) nets (DR: 6.4, 95% CI 1.1–36.0, p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus.

Conclusion

The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets.

Graphical Abstract
New mosquito repellency bioassay for evaluation of repellents and pyrethroids using an attractive blood-feeding device
Authors: Morimoto Yasue , Kawada Hitoshi , Kuramoto Kan-ya , Mitsuhashi Takuya , Saitoh Toshinobu , Minakawa Noboru
Published: March 2021

Background

With the increasing threat of the worldwide spread of mosquito-borne infectious diseases, consumer interest in anti-mosquito textiles that protect against mosquito bites is also increasing. Accordingly, repellent- or insecticide-treated textiles are gaining popularity. The standardization of commercial textile products is, therefore, indispensable for an authentic and objective evaluation of these products. Here we report a textile testing method using an artificial blood-feeding system that does not involve human volunteers or live animals, which aligns with the policy of protecting human and animal welfare.

Methods

The attractive blood-feeding device (ABFD) was designed using the Hemotek® membrane feeding system. The repellency of DEET, icaridin and permethrin was assayed using unfed female adults of Aedes albopictus (Skuse) under two different test conditions, namely choice and no-choice tests. The choice test consisted of two feeding units, one chemically treated and untreated, that were installed on the ABFD; mosquitoes attracted to and resting on the feeding units were counted and the overall blood-feeding rates recorded. The no-choice test consisted of two feeding units treated with the same chemical that were installed on the ABFD; mosquitoes attracted to and resting on the feeding units were counted and the blood-feeding rates were recorded. A control test was conducted using two feeding units, both sides of which were untreated.

Results

In the choice test, high repellency (> 95% inhibition of resting on the treated surface) of 1% DEET and 2% icaridin was observed, whereas 2% permethrin was not an effective repellent. Also, high blood-feeding inhibition (> 95%) was observed for 2% DEET and 2% icaridin. In the no-choice test, high repellency was observed for 1% DEET and 2% icaridin, whereas the repellency of 2% permethrin was low. Also, high blood-feeding inhibition was observed for 2% DEET, 4% icaridin and 2% permethrin.

Conclusions

The accuracy and reproducibility of the developed method demonstrate that the ABFD may be widely used for fundamental experiments in the field of mosquito physiology, for the development of new repellent chemicals and in evaluation studies of mosquito repellent products, such as anti-mosquito textiles. The further development of the membrane and feeding unit systems will enable a more practical evaluation of mosquito repellents and blood-feeding inhibitors, such as pyrethroids.

Graphical Abstract
Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early signature of successful treatment
Authors: Oliver James , Nair Nisha , Orozco Gisela , Smith Samantha , Hyrich Kimme L. , Morgan Ann , Isaacs John , Wilson Anthony G. ,   BRAGGSS, Barton Anne , Plant Darren
Published: March 2021

Background

Despite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. This study aimed to identify transcriptome-based biomarkers of adalimumab response in rheumatoid arthritis (RA) to aid timely switching in non-responder patients and provide a better mechanistic understanding of the pathways involved in response/non-response.

Methods

The Affymetrix Human Transcriptome Array 2.0 (HTA) was used to measure the transcriptome in whole blood at pre-treatment and at 3 months in EULAR good- and non-responders to adalimumab therapy. Differential expression of transcripts was analysed at the transcript level using multiple linear regression. Differentially expressed genes were validated in independent samples using OpenArray™ RT-qPCR.

Results

In total, 813 transcripts were differentially expressed between pre-treatment and 3 months in adalimumab good-responders. No significant differential expression was observed between good- and non-responders at either time-point and no significant changes were observed in non-responders between time-points. OpenArray™ RT-qPCR was performed for 104 differentially expressed transcripts in good-responders, selected based on magnitude of effect or p value or based on prior association with RA or the immune system, validating differential expression for 17 transcripts.

Conclusions

An early transcriptome signature of DAS28 response to adalimumab has been identified and replicated in independent datasets. Whilst treat-to-target approaches encourage early switching in non-responsive patients, registry evidence suggests that this does not always occur. The results herein could guide the development of a blood test to distinguish responders from non-responders at 3 months and support clinical decisions to switch non-responsive patients to an alternative therapy.
Integrating transcriptome-wide association study and mRNA expression profile identified candidate genes related to hand osteoarthritis
Authors: Xu Jiawen , Zeng Yi , Si Haibo , Liu Yuan , Li Mingyang , Zeng Junfeng , Shen Bin
Published: March 2021

Background

Osteoarthritis (OA) is a common skeletal system disease that has been partially attributed to genetic factors. The hand is frequently affected, which seriously affects the patient’s quality of life. However, the pathogenetic mechanism of hand osteoarthritis (hand OA) is still elusive.

Methods

A genome-wide association study (GWAS) summary of hand OA was obtained from the UK Biobank dataset, which contains data from a total of 452,264 White British individuals, including 37,782 OA patients. The transcriptome-wide association study (TWAS) of hand OA was performed using FUnctional Summary-based ImputatiON (FUSION) with the skeletal muscle and blood as gene expression references. The significant genes identified by TWAS were further subjected to gene set enrichment analysis (GSEA) with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the genes and gene sets identified by our TWAS with that of a knee OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles in OA. The mRNA expression profiles of 18 normal knee cartilages and 20 OA knee cartilages were acquired from the Gene Expression Omnibus database (accession number: GSE114007).

Results

TWAS identified 177 genes with P < 0.05 for the skeletal muscle, including ANKRD44 (P = 0.0001), RIC3 (P = 0.0003), and AC005154.6 (P = 0.0004). TWAS identified 423 genes with P < 0.05 for the blood, including CRIM1 (P = 0.0002), ZNF880 (P = 0.0002), and NCKIPSD (P = 0.0003). After comparing the results of the TWAS to those of the mRNA expression profiling of OA, we identified 5 common genes, including DHRS3 (log2fold = − 1.85, P = 3.31 × 10− 9) and SKP2 (log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003) and cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling, including protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS = 0.02, PmRNA = 1.18 × 10− 4), and cytoplasm (PTWAS = 0.0183, PmRNA = 0.0048).

Conclusion

In this study, we identified 5 candidate genes and 6 GO terms related to hand OA, which may help to uncover the pathogenesis of hand OA. It should be noted that the possible difference in the gene expression profiles between hand OA and knee OA may affect our study results, which should be interpreted with caution.
Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Authors: Hattori Sachiko , Nomoto Kazuomi , Suzuki Tomohiko , Hayashi Seishu
Published: March 2021

Background

Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis.

Method

We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH).

Results

In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography.

Conclusion

Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.
Association between fasting insulin and C-reactive protein among adults without diabetes using a two-part model: NHANES 2005–2010
Authors: Missel Amanda L. , Saslow Laura R. , Griauzde Dina H. , Marvicsin Donna , Sen Ananda , Richardson Caroline R. , Liu Xuefeng
Published: March 2021

Introduction

Chronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment.

Methods

This study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model.

Results

The final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012).

Conclusion

This study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.
Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice
Authors: Gomez-Flores R. , Gutierrez-Leal I. , Caballero-Hernández D. , Orozco-Flores A. , Tamez-Guerra P. , Tamez-Guerra R. , Rodríguez-Padilla C.
Published: March 2021

Objective

Lymphocytes express tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine, norepinephrine and epinephrine. This suggests a broader role for cathecholamines in lymphocyte function, as well as the potential secretion of catecholamines by tumors of lymphoid origin. Our aim was to evaluate the expression ofThby murine lymphoma cells in an in vivo mouse model. For this, L5178Y-R lymphoma cells were implanted in nerve-intact and sympathectomized male BALB/c mice. RelativeThgene expression in tumor and brain was determined by quantitative PCR. Body composition, tumor volume, and plasma TH1/TH2/TH17 cytokines were also evaluated as markers of tumor-host condition and anti-tumor immune response in absence of adrenergic innervation.

Results

We found a significant (p = 0.045) 3.3-fold decrease ofThgene expression in tumor and a non-significant (p = 0.60) 6.9-fold increase in brain after sympathectomy. Sympathectomized mice also showed a significant increase in tumor mass at days 18 (p = 0.032) and 28 (p = 0.022) and increased interscapular fat (p = 0.04). TH1/TH2 and TH17 cytokines levels in plasma from sympathectomized tumor-bearing mice were not different from control mice.

Conclusion

The L5178Y-R lymphoma does not expressThduring in vivo progression.
An acute viral hepatitis epidemic: does ultrasound help the pediatrician?
Authors: Arooj Sadaf , Mukhtar Muhammad Umer , Abbas Farnaz
Published: March 2021

Objective

Acute viral hepatitis (AVH) caused by hepatitis virus A and hepatitis virus E is one of the many epidemics that plague third world countries like Pakistan. The serological tests required for the diagnosis of acute viral hepatitis may be unavailable or unaffordable to the denizens of a developing country like Pakistan. In such a scenario, the clinical manifestations and the ultrasonographic findings are the only diagnostic criteria usually present and these can be used to support a clinical diagnosis. This study aims to judge the utility of ultrasound in the diagnosis of AVH.

Results

Among the forty-seven subjects of this study, gall bladder wall thickening (GWT) was the most common radiological finding seen in 39 (82.9%) patients. Pericholecystic edema was the second most common finding, seen in 31 (65.9%) patients. Starry sky appearance of the liver was observed in 30 (63.8) patients. Hepatomegaly and ascites were seen in 28 (59.5%) and 25 (53.2%) of the patients, respectively. The ultrasonographic findings of GWT, pericholecystic edema, and starry sky appearance of the liver were the most common ultrasonographic findings associated with AVH.
Characterization, stability and hyperstability of multi-quadratic–cubic mappings
Authors: Bodaghi Abasalt , Fošner Ajda
Published: March 2021

In this paper, we unify the system of functional equations defining a multi-quadratic–cubic mapping to a single equation. Applying a fixed point theorem, we study the generalized Hyers–Ulam stability of multi-quadratic–cubic mappings. As a result, we investigate the hyperstability of multi-quadratic–cubic mappings in some senses.
The first initial-boundary value problem of parabolic Monge–Ampère equations outside a bowl-shaped domain
Authors: Dai Limei , Cheng Huihui
Published: March 2021

In this paper, we study the parabolic Monge–Ampère equations $-u_{t}\det (D^{2}u)=g$
−

u
t

det
(

D
2

u
)
=
g
outside a bowl-shaped domain with g being the perturbation of $g_{0}(|x|)$

g
0

(
|
x
|
)
at infinity. Under the weaker conditions compared with the problem outside a cylinder, we obtain the existence and uniqueness of viscosity solutions with asymptotic behavior for the first initial-boundary value problem by using the Perron method.
Existence and uniqueness results on time scales for fractional nonlocal thermistor problem in the conformable sense
Authors: Agarwal P. , Sidi Ammi M. R. , Asad J.
Published: March 2021

We study a conformable fractional nonlocal thermistor problem on time scales. Under an appropriate nonrestrictive condition on the resistivity function, we establish existence and uniqueness results. The proof is based on the use of Schauder’s point fixed theorem.
Experimental Study on Basic Mechanical Properties of Core-Column Non-mortar Aerated Concrete Block Masonry
Authors: Pi Tianxiang , Du Zhongheng , Zhang Huchen , Wang Sicheng
Published: March 2021

Autoclaved aerated concrete (AAC) block masonry has been widely used for bearing walls of multi-story buildings or non-bearing walls of high-rise buildings because of its unique advantages, such as lightweight, low pollution output, and excellent thermal insulation performance. However, traditional AAC block masonry has the disadvantages of high water absorption, poor adhesion to mortar, and low construction efficiency. In order to improve the performance of traditional AAC masonry, this paper proposed a new kind of mortar-free AAC block masonry with concrete core-columns. Fundamental mechanical properties of compression and shear were studied. We divided a total of 16 compression specimens into four groups according to different hollow ratios and strength grades of the block, and eight shear specimens into two groups based on different hollow ratios. Each specimen consists of three-layer blocks with two core columns at the point of quadri-section. The diameters of columns were, respectively, 100 mm and 80 mm. The specimens were loaded at a constant speed to evaluate their bearing capacity, displacement response, crack development, and damage state. The formula of the average values and design values of the compressive and shear strength of masonry were obtained statistically. The stress–strain constitutive relation of masonry expressed by a three-stage curve was presented. Furthermore, the result of numerical analysis using the ABAQUS finite element program aligned well with the experimental results. The compressive strength and shear strength of the new type of masonry are no less than traditional AAC masonry, and new masonry has higher construction efficiency and more stable strength.
Transcriptomic analysis reveals the molecular mechanisms of rumen wall morphological and functional development induced by different solid diet introduction in a lamb model
Authors: Sun Daming , Yin Yuyang , Guo Changzheng , Liu Lixiang , Mao Shengyong , Zhu Weiyun , Liu Junhua
Published: March 2021

Background

This study aimed to elucidate the molecular mechanisms of solid diet introduction initiating the cellular growth and maturation of rumen tissues and characterize the shared and unique biological processes upon different solid diet regimes.

Methods

Twenty-four Hu lambs were randomly allocated to three groups fed following diets: goat milk powder only (M, n = 8), goat milk powder + alfalfa hay (MH, n = 8), and goat milk powder + concentrate starter (MC, n = 8). At 42 days of age, the lambs were slaughtered. Ruminal fluid sample was collected for analysis of concentration of volatile fatty acid (VFA) and microbial crude protein (MCP). The sample of the rumen wall from the ventral sac was collected for analysis of rumen papilla morphology and transcriptomics.

Results

Compared with the M group, MH and MC group had a higher concentration of VFA, MCP, rumen weight, and rumen papilla area. The transcriptomic results of rumen wall showed that there were 312 shared differentially expressed genes (DEGs) between in “MH vs. M” and “MC vs. M”, and 232 or 796 unique DEGs observed in “MH vs. M” or “MC vs. M”, respectively. The shared DEGs were most enriched in VFA absorption and metabolism, such as peroxisome proliferator-activated receptor (PPAR) signaling pathway, butanoate metabolism, and synthesis and degradation of ketone bodies. Additionally, a weighted gene co-expression network analysis identified M16 (2,052 genes) and M18 (579 genes) modules were positively correlated with VFA and rumen wall morphology. The M16 module was mainly related to metabolism pathway, while the M18 module was mainly associated with signaling transport. Moreover, hay specifically depressed expression of genes involved in cytokine production, immune response, and immunocyte activation, and concentrate starter mainly altered nutrient transport and metabolism, especially ion transport, amino acid, and fatty acid metabolism.

Conclusions

The energy production during VFA metabolism may drive the rumen wall development directly. The hay introduction facilitated establishment of immune function, while the concentrate starter enhanced nutrient transport and metabolism, which are important biological processes required for rumen development.
Genomics-driven drug discovery based on disease-susceptibility genes
Authors: Sonehara Kyuto , Okada Yukinori
Published: March 2021

Genome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene–disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.
Political economy analysis of the performance‐based financing programme in Afghanistan
Authors: Salehi Ahmad Shah , Blanchet Karl , Vassall Anna , Borghi Josephine
Published: March 2021

Background

Performance-based financing (PBF) has attracted considerable attention in recent years in low and middle-income countries. Afghanistan’s Ministry of Public Health (MoPH) implemented a PBF programme between 2010 and 2015 to strengthen the utilisation of maternal and child health services in primary health facilities. This study aimed to examine the political economy factors influencing the adoption, design and implementation of the PBF programme in Afghanistan.

Methods

Retrospective qualitative research methods were employed using semi structured interviews as well as a desk review of programme and policy documents. Key informants were selected purposively from the national level (n = 9), from the province level (n = 6) and the facility level (n = 15). Data analysis was inductive as well as deductive and guided by a political economy analysis framework to explore the factors that influenced the adoption and design of the PBF programme. Thematic content analysis was used to analyse the data.

Results

The global policy context, and implementation experience in other LMIC, shaped PBF and its introduction in Afghanistan. The MoPH saw PBF as a promise of additional resources needed to rebuild the country’s health system after a period of conflict. The MoPH support for PBF was also linked to their past positive experience of performance-based contracting. Power dynamics and interactions between PBF programme actors also shaped the policy process. The PBF programme established a centralised management structure which strengthened MoPH and donor ability to manage the programme, but overlooked key stakeholders, such as provincial health offices and non-state providers. However, MoPH had limited input in policy design, resulting in a design which was not well tailored to the national setting.

Conclusions

This study shows that PBF programmes need to be designed and adapted according to the local context, involving all relevant actors in the policy cycle. Future studies should focus on conducting empirical research to not only understand the multiple effects of PBF programmes on the performance of health systems but also the main political economy dynamics that influence the PBF programmes in different stages of the policy process.
Unveiling novel inhibitors of dopamine transporter via in silico drug design, molecular docking, and bioavailability predictions as potential antischizophrenic agents
Authors: Olasupo Sabitu Babatunde , Uzairu Adamu , Shallangwa Gideon Adamu , Uba Sani
Published: March 2021

Background

The inhibition of dopamine transporter is known to play a significant role in the treatment of schizophrenia-related and other mental disorders. In a continuing from our previous study, computational drug design approach, molecular docking simulation, and pharmacokinetics study were explored for the identification of novel inhibitors dopamine transporter as potential Antischizophrenic agents. Consequently, thirteen (13) new inhibitors of dopamine transporter were designed by selecting the molecule with serial number 39 from our previous study as the template molecule because  it exhibits good pharmacological attributes.

Results

Molecular docking simulation results revealed excellent molecular interactions between the protein target (PDB: 4m48) and the ligands (designed inhibitors) with major interactions that involved hydrogen bonding and hydrophobic interactions. Also, some of the designed inhibitors displayed a superior binding affinity range from − 10.0 to − 10.7 kcal/mol compared to the referenced drug (Lumateperone) with a binding affinity of − 9.7 kcal/mol. Computed physicochemical parameters showed that none of the designed inhibitors including the referenced drug violate Lipinski’s rule of five indicating that all the designed inhibitors would be orally bioavailable as potential drug candidates. Similarly, the ADMET/pharmacokinetics evaluations of some designed inhibitors revealed that they possessed good absorption, distribution, metabolism and excretion properties and none of the inhibitors is neither carcinogens nor toxic toward human ether-a-go-go related gene (hERG I) inhibitor or skin sensitization. Likewise, the BOILED-Egg graphics unveils that all the designed inhibitors demonstrate a high probability to be absorbed by the human gastrointestinal tract and could permeate into the brain. Besides, the predicted bioactive parameters suggested that all the selected inhibitors would be active as drug candidates. Furthermore, the synthetic accessibility scores for all the selected inhibitors and referenced drug lied within the easy zone (i.e., between 1–4) with their computed values range from 2.55 to 3.92, this implies that all the selected inhibitors would be very easy to synthesize in the laboratory.

Conclusions

Hence, all the designed inhibitors having shown excellent pharmacokinetics properties and good bioavailabilities attributes with remarkable biochemical interactions could be developed and optimized as novel Antischizophrenic agents after the conclusion of other experimental investigations.
Distributed acoustic sensing for shallow seismic investigations and void detection
Authors: Abukrat Yarin , Reshef Moshe
Published: March 2021

During the past few decades, fiber-optic-based distributed acoustic sensing (DAS) has emerged as an affordable, easy-to-deploy, reliable, and noninvasive technique for high-resolution seismic sensing. We have determined that fiber deployments dedicated to near-surface seismic applications, commonly used for the detection and localization of voids, can be used effectively with conventional processing techniques. We tested a variety of small sources in different geologic environments. These sources, operated on and below the surface, were recorded by horizontal and vertical DAS arrays. Our results and comparisons to data acquired by vertical-component geophones demonstrate that DAS may be sufficient for acquiring near-surface seismic data. Furthermore, we tried to address the issue of directional sensing by DAS arrays and use it to solve the problem of wave-mode separation. Records acquired by a unique acquisition setup suggest that one can use the nature of standard DAS systems as uniaxial strainmeters to record separated wave modes. Finally, we applied two seismic methods on DAS data acquired at a test site: multichannel analysis of surface waves (MASW) and shallow diffraction imaging. These methods allowed us to determine the feasibility of using DAS systems for imaging shallow subsurface voids. MASW was used to uncover anomalies in the S-wave velocity, whereas shallow diffraction imaging was applied to identify the location of the void. The results we obtained illustrate that by using these methods we are able to accurately detect the true location of the void.
Improved estimation of ice and water contents in alpine permafrost through constrained petrophysical joint inversion: The Hoher Sonnblick case study
Authors: Steiner Matthias , Wagner Florian M. , Maierhofer Theresa , Schöner Wolfgang , Flores Orozco Adrián
Published: March 2021

Quantitative estimation of subsurface water and ice content values is critical for the understanding and modeling of permafrost evolution in alpine regions. Geophysical methods permit the assessment of subsurface conditions in a noninvasive and quasicontinuous manner; in particular, the combination of seismic refraction tomography (SRT) and electrical resistivity tomography (ERT) through a petrophysical model can quantitatively estimate ground water and ice content values. For the Hoher Sonnblick study area (3106 m.a.s.l., Austrian Alps), we have investigated the improved estimation of water and ice content values based on SRT, ERT, and ground-penetrating radar data collected in June and October 2019. We solve for the water and ice content values following different approaches, namely, (1) the independent inversion and subsequent transformation of the imaging results to the target parameters through a petrophysical model and (2) the petrophysical joint inversion (PJI) of the data sets. Supported by a synthetic study, we determine that the incorporation of structural and porosity constraints in the PJI allows for an improved quantitative characterization of subsurface conditions. For our measurements at Hoher Sonnblick, the constrained PJI resolves a shallow debris layer characterized by high air content and porosity, on top of a layer with lower porosity corresponding to fractured gneiss, and the bedrock layer with the lowest porosity. For both time steps, we find high water content at the lower end of the investigated area. Substantial variations in the subsurface ice content resolved between June and October 2019 indicate a correlation between the high water content and the meltwater discharge within the debris layer. Our results demonstrate that the constrained PJI permits an improved characterization of subsurface hydrologic parameters in alpine permafrost environments.
Well-logging evaluation of the shale gas potential in the lower Silurian Longmaxi Formation, Weiyuan, southern Sichuan Basin, China
Authors: Zhou Guangzhao , Hu Zhiming , Liu Xiangui , Duan Xianggang , Chang Jin
Published: March 2021

Recent observations of shale gas breakthroughs in the Weiyuan marine shale gas play in the Sichuan Basin have attracted great interest. To better understand these breakthroughs, we have used core description, cyro-focused ion beam scanning electron microscopy data, X-ray diffraction data, organic geochemistry, and well-logging data to better understand the reservoir characteristics carbonaceous shale, calcareous shale, and siliceous shale lithology, with a focus on organic-rich shale units. We find that conventional well-log methods are effective in mapping the spatial distribution of organic-rich shale in the Weiyuan area where the total organic carbon (TOC) content in the Longmaxi Formation ranges from 1.35% to 6.95%, averaging 4.42%. The kerogen is type I-II, and the vitrinite reflectance (Ro) is greater than 2.57%, which indicates that the formation is susceptible to shale gas accumulation. The clay mineral content ranges from 48 to 63 wt% (avg. 51 wt%) with illite and chlorite averaging 73.8% and 25.7%, respectively. The brittle mineral quartz and plagioclase content ranges from 32 to 61 wt% (avg. 47 wt%). Compared to the surrounding lithologic units, the marine shale exhibits relatively high gamma ray, neutron, sonic, resistivity, potassium, and uranium (U) values and relatively low density, photoelectric effect, and thorium/U values, allowing us to construct crossplots to define the units of interest. Using the same process, we quantify the TOC content providing a spatial distribution of organic-rich shale using conventional well logging.
Submarine landslide origin of a tsunami at the Black Sea coast: Evidence based on swath bathymetry and 3D seismic reflection data
Authors: Tishchenko Ilya , Tari Gabor , Fallah Mohammad , Floodpage Jonathan
Published: March 2021

Tsunami waves were observed along the Bulgarian Black Sea coastline on 7 May 2007. The maximum rise and fall of the sea level were 1.2 and 2.0 m, respectively, with wave oscillations between 4 and 8 min. At first, submarine landsliding and then later on atmospheric disturbance were suggested as the cause of the tsunami. Numerical modeling, assuming a landslide displacing 30–60 million m3 material on the slope with a thickness range of more than 20–40 m, could reproduce the main characteristics of the recorded tsunami. In this early model, the landslide initiated on the shelf at a water depth of 100 m with a runout of approximately 20 km into 1000 m water depth. Subsequent and recent numerical modeling suggested that the failure may have initiated on the slope, anywhere between 200 and 1500 m seafloor depth. The runout of the transported sediments in these latest model was at 1850 m water depth. Just a few years after the tsunami, OMV and its joint venture partners, TOTAL and Repsol, acquired modern deepwater data sets in the same area where the submarine landsliding was assumed to occur. These data sets included multibeam swath bathymetry area and 3D reflection seismic data. These data sets offer a possibility to establish the presence of speculative submarine landslide responsible for the tsunami, with its geometry and nature. Our results provide direct evidence for the occurrence of large nonseismic catastrophic sediment failures along the Bulgarian coast. In this study, we illustrate Quaternary submarine landslides on 3D seismic reflection data immediately below the one responsible for the 2007 event; we also briefly point out the potential interpretation pitfall related to sediment waves and mass transport complexes.
Development and Evaluation of a Navigation-Based, Multilevel Intervention to Improve the Delivery of Timely, Guideline-Adherent Adjuvant Therapy for Patients With Head and Neck Cancer
Authors: Graboyes Evan M. , Sterba Katherine R. , Li Hong , Warren Graham W. , Alberg Anthony J. , Calhoun Elizabeth A. , Nussenbaum Brian , McCay Jessica , Marsh Courtney H. , Osazuwa-Peters Nosayaba , Neskey David M. , Kaczmar John M. , Sharma Anand K. , Harper Jennifer , Day Terry A. , Hughes-Halbert Chanita
Published: March 2021

PURPOSE:

More than half of patients with head and neck squamous cell carcinoma (HNSCC) experience a delay initiating guideline-adherent postoperative radiation therapy (PORT), contributing to excess mortality and racial disparities in survival. However, interventions to improve the delivery of timely, equitable PORT among patients with HNSCC are lacking. This study (1) describes the development of NDURE (Navigation for Disparities and Untimely Radiation thErapy), a navigation-based multilevel intervention (MLI) to improve guideline-adherent PORT and (2) evaluates its feasibility, acceptability, and preliminary efficacy.

METHODS:

NDURE was developed using the six steps of intervention mapping (IM). Subsequently, NDURE was evaluated by enrolling consecutive patients with locally advanced HNSCC undergoing surgery and PORT (n = 15) into a single-arm clinical trial with a mixed-methods approach to process evaluation.

RESULTS:

NDURE is a navigation-based MLI targeting barriers to timely, guideline-adherent PORT at the patient, healthcare team, and organizational levels. NDURE is delivered via three in-person navigation sessions anchored to case identification and surgical care transitions. Intervention components include the following: (1) patient education, (2) travel support, (3) a standardized process for initiating the discussion of expectations for PORT, (4) PORT care plans, (5) referral tracking and follow-up, and (6) organizational restructuring. NDURE was feasible, as judged by accrual (88% of eligible patients [100% Blacks] enrolled) and dropout (n = 0). One hundred percent of patients reported moderate or strong agreement that NDURE helped solve challenges starting PORT; 86% were highly likely to recommend NDURE. The rate of timely, guideline-adherent PORT was 86% overall and 100% for Black patients.

CONCLUSION:

NDURE is a navigation-based MLI that is feasible, is acceptable, and has the potential to improve the timely, equitable, guideline-adherent PORT.
Hidden energy flows in strongly coupled nonequilibrium systems
Authors: Large Steven J. , Sivak David A.
Published: March 2021

Quantifying the flow of energy within and through fluctuating nanoscale systems poses a significant challenge to understanding microscopic biological machines. A common approach involves coarse graining, which allows a simplified description of such systems. This has the side effect of inducing so-called hidden contributions (due to sub-resolution dynamics) that complicate the resulting thermodynamics. Here we develop a thermodynamically consistent theory describing the nonequilibrium excess power internal to autonomous systems, and introduce a phenomenological framework to quantify the hidden excess power associated with their operation. We confirm our theoretical predictions in numerical simulations of a minimal model for both a molecular transport motor and a rotary motor.
An Innovative Way to Achieve Safe Lung Deflation During One-Lung Ventilation in a Potential Coronavirus Disease 2019 Patient: A Case Report
Authors: Magharious Peter , Cvetkovic Draginja , Weigel Tracey
Published: March 2021

A novel coronavirus pandemic may be particularly hazardous to health care workers. Airway management is an aerosol-producing high-risk procedure. To minimize the production of airborne droplets, including pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the endotracheal tube during procedures requiring lung deflation, we devised a technique to mitigate the risk of infection transmission to health care personnel.
Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome
Authors: Mao Mao , Popli Tanav , Jeanne Marion , Hoff Kendall , Sen Saunak , Gould Douglas B.
Published: March 2021

Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that can affect any organ but typically involves the cerebral vasculature, eyes, kidneys and skeletal muscles. In recent years, patient advocacy and family support groups have united under the name of Gould syndrome. The manifestations of Gould syndrome are highly variable, and animal studies suggest that allelic heterogeneity and genetic context contribute to the clinical variability. We previously characterized a mouse model of Gould syndrome caused by a Col4a1 mutation in which the severities of ocular anterior segment dysgenesis (ASD), myopathy and intracerebral hemorrhage (ICH) were dependent on genetic background. Here, we performed a genetic modifier screen to provide insight into the mechanisms contributing to Gould syndrome pathogenesis and identified a single locus [modifier of Gould syndrome 1 (MoGS1)] on Chromosome 1 that suppressed ASD. A separate screen showed that the same locus ameliorated myopathy. Interestingly, MoGS1 had no effect on ICH, suggesting that this phenotype could be mechanistically distinct. We refined the MoGS1 locus to a 4.3 Mb interval containing 18 protein-coding genes, including Fn1, which encodes the extracellular matrix component fibronectin 1. Molecular analysis showed that the MoGS1 locus increased Fn1 expression, raising the possibility that suppression is achieved through a compensatory extracellular mechanism. Furthermore, we found evidence of increased integrin-linked kinase levels and focal adhesion kinase phosphorylation in Col4a1 mutant mice that is partially restored by the MoGS1 locus, implicating the involvement of integrin signaling. Taken together, our results suggest that tissue-specific mechanistic heterogeneity contributes to the variable expressivity of Gould syndrome and that perturbations in integrin signaling may play a role in ocular and muscular manifestations.
Picornavirus 3C – a protease ensuring virus replication and subverting host responses
Authors: Yi Jiamin , Peng Jiangling , Yang Wenping , Zhu Guoqiang , Ren Jingjing , Li Dan , Zheng Haixue
Published: March 2021

The protease 3C is encoded by all known picornaviruses, and the structural features related to its protease and RNA-binding activities are conserved; these contribute to the cleavage of viral polyproteins and the assembly of the viral RNA replication complex during virus replication. Furthermore, 3C performs functions in the host cell through its interaction with host proteins. For instance, 3C has been shown to selectively ‘hijack’ host factors involved in gene expression, promoting picornavirus replication, and to inactivate key factors in innate immunity signaling pathways, inhibiting the production of interferon and inflammatory cytokines. Importantly, 3C maintains virus infection by subtly subverting host cell death and modifying critical molecules in host organelles. This Review focuses on the molecular mechanisms through which 3C mediates physiological processes involved in virus–host interaction, thus highlighting the picornavirus-mediated pathogenesis caused by 3C.
Education and training to support physiotherapists working in dementia care: a scoping review protocol
Authors: O'Sullivan Trish , Foley Tony , McVeigh Joseph G. , Timmons Suzanne
Published: March 2021

Background: The care of people with dementia is of global concern. Physiotherapeutic intervention can be of benefit to patients with dementia. Physiotherapists can play a role in assessment, falls prevention, pain management and gait re-education. Dementia care forms a significant part of the workload of a physiotherapist. However, there is a paucity of evidence on what constitutes effective education and training for physiotherapists working in dementia care.

Objective: This scoping review aims to explore and map the evidence on education and training for

physiotherapists working in dementia care.

Inclusion criteria: Studies that explore dementia training and/or education for physiotherapists or for multidisciplinary teams, in which physiotherapists have been included. Studies that explore student physiotherapy training will also be considered. Systematic reviews, qualitative, quantitative, mixed methods studies, case studies and observational studies will be included.

Methods: This scoping review will follow the Joanna Briggs Institute (JBI) methodology for scoping reviews. Databases to be searched as part of this review include: Medline, Cochrane Database of Systematic Reviews, SocINDEX, CINAHL and, PsycINFO, with no limitation on publication date. Google Scholar and Open-Grey will be searched for grey literature, limited to the first 100 searches.  Titles and abstracts will be screened for inclusion and identified full texts reviewed independently by two reviewers. Data will be extracted using a draft data extraction tool based on the JBI data extraction tool. A chronological narrative synthesis of the data will outline how the results relate to the aims and objective of this scoping review.
Factors like Dilution and Mixing Influence Enzymatic Reactions
Authors: Basha Syed Mahin , Erumalla Venkatanagraraju
Published: March 2021

Enzyme-catalyzed reactions were influenced by many factors. The enzyme reacts with the substrate and converts it into products. Enzymes are influenced by temperature, pH, enzyme concentration, and substrate concentration. This paper evaluates the hypothesis of factors that may influence enzyme activity. Two more factors that affects enzyme activity are dilution and mixing. In enzyme-substrate reactions, the small amount of dilution and mixing will not affect the enzyme activity. Dilution and mixing do not slowdowns the enzyme reaction but it enhances the enzymatic reaction up to a certain limit. Increase in dilution results in less interaction of enzyme substrate, which causes a decrease in the rate of reactions. To the best of our knowledge, this is the first report to shows that, factors like mixing and dilution also affect enzyme and substrate reactions.
Improving Reliability Estimation for Individual Numeric Predictions: A Machine Learning Approach
Authors: Adomavicius Gediminas , Wang Yaqiong
Published: March 2021

Numerical predictive modeling is widely used in different application domains. Although many modeling techniques have been proposed, and a number of different aggregate accuracy metrics exist for evaluating the overall performance of predictive models, other important aspects, such as the reliability (or confidence and uncertainty) of individual predictions, have been underexplored. We propose to use estimated absolute prediction error as the indicator of individual prediction reliability, which has the benefits of being intuitive and providing highly interpretable information to decision makers, as well as allowing for more precise evaluation of reliability estimation quality. As importantly, the proposed reliability indicator allows the reframing of reliability estimation itself as a canonical numeric prediction problem, which makes the proposed approach general-purpose (i.e., it can work in conjunction with any outcome prediction model), alleviates the need for distributional assumptions, and enables the use of advanced, state-of-the-art machine learning techniques to learn individual prediction reliability patterns directly from data. Extensive experimental results on multiple real-world data sets show that the proposed machine learning-based approach can significantly improve individual prediction reliability estimation as compared with a number of baselines from prior work, especially in more complex predictive scenarios.