bluuebunny/crossref_metadata_2025 huggingface dataset:
Early spinal cord pseudoatrophy in interferon‐beta‐treated multiple sclerosis
Authors: Matusche Britta , Litvin Ludmila , Schneider Ruth , Bellenberg Barbara , Mühlau Mark , Pongratz Viola , Berthele Achim , Groppa Sergiu , Muthuraman Muthuraman , Zipp Frauke , Paul Friedemann , Wiendl Heinz , Meuth Sven G. , Sämann Philipp , Weber Frank , Linker Ralf A. , Kümpfel Tania , Gold Ralf , Lukas Carsten
Published: November 2022

Background and purpose

Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease‐modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain.

Methods

A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon‐beta therapy (n = 84) and untreated patients (n = 45).

Results

Patients treated with interferon‐beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year.

Conclusions

These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon‐beta treatment.
Microevolutionary mechanism of high‐altitude adaptation in Tibetan chicken populations from an elevation gradient
Authors: Zhong Hai‐An , Kong Xiao‐Yan , Zhang Ya‐Wen , Su Yan‐Kai , Zhang Bo , Zhu Li , Chen Hua , Gou Xiao , Zhang Hao
Published: November 2022

As an indigenous breed, the Tibetan chicken is found in highland regions and shows physiological adaptations to high altitude; however, the genetic changes that determine these adaptations remain elusive. We assumed that the microevolution of the Tibetan chicken occurred from lowland to highland regions with a continuous elevation range. In this study, we analyzed the genome of 188 chickens from lowland areas to the high‐altitude regions of the Tibetan plateau with four altitudinal levels. Phylogenetic analysis revealed that Tibetan chickens are significantly different from other altitude chicken populations. Reconstruction of the demographic history showed that the migration and admixture events of the Tibetan chicken occurred at different times. The genome of the Tibetan chicken was also used to analyze positive selection pressure that is associated with high‐altitude adaptation, revealing the well‐known candidate gene that participates in oxygen binding (HBAD), as well as other novel potential genes (e.g., HRG and ANK2) that are related to blood coagulation and cardiovascular efficiency. Our study provides novel insights regarding the evolutionary history and microevolution mechanisms of the high‐altitude adaptation in the Tibetan chicken.
Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease
Authors: Wang Jian , Liu Jiacheng , Liu Yilin , Xue Ruifei , Zhan Jie , Jiang Suling , Wang Li , Yan Xiaomin , Xiong Yali , Xia Juan , Yin Shengxia , Tong Xin , Chen Yuxin , Li Jie , Huang Rui , Wu Chao
Published: November 2022

Background

The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB‐NAFLD patients.

Methods

The study retrospectively included treatment‐naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis‐4 score (FIB‐4), NAFLD fibrosis score (NFS), and transient elastography.

Results

Among 1226 CHB‐NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB‐NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p = 0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p < 0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p = 0.002) than nonlean patients. The values of APRI, FIB‐4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (−3.0 vs. −2.6, p < 0.001) and lower proportions (12.6% vs. 21.1%, p = 0.003) of advanced fibrosis (NFS ≥ −1.5) than nonlean patients. Similar results were observed in HBeAg‐positive and HBeAg‐negative subgroups.

Conclusions

Nearly a quarter of CHB‐NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB‐NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg‐positive proportions.

Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.
Protein kinase D3 promotes neutrophil migration during viral infection
Authors: Veazey Janelle M , Wong Gordon S , Eliseeva Sophia I , Smyth Timothy R , Chapman Timothy J , Lim Kihong , Kim Minsoo , Georas Steve N
Published: November 2022

Protein kinase D (PKD) is a serine/threonine kinase family with three isoforms (PKD1–3) that are expressed in most cells and implicated in a wide array of signaling pathways, including cell growth, differentiation, transcription, secretion, polarization and actin turnover. Despite growing interest in PKD, relatively little is known about the role of PKD in immune responses. We recently published that inhibiting PKD limits proinflammatory cytokine secretion and leukocyte accumulation in mouse models of viral infection, and that PKD3 is highly expressed in the murine lung and immune cell populations. Here we focus on the immune‐related phenotypes of PKD3 knockout mice. We report that PKD3 is necessary for maximal neutrophil accumulation in the lung following challenge with inhaled polyinosinic:polycytidylic acid, a double‐stranded RNA, as well as following influenza A virus infection. Using reciprocal bone marrow chimeras, we found that PKD3 is required in the hematopoietic compartment for optimal neutrophil migration to the lung. Ex vivo transwell and chemokinesis assays confirmed that PKD3−/− neutrophils possess an intrinsic motility defect, partly because of reduced surface expression of CD18, which is critical for leukocyte migration. Finally, the peak of neutrophilia was significantly reduced in PKD3−/− mice after lethal influenza A virus infection. Together, these results demonstrate that PKD3 has an essential, and nonredundant, role in promoting neutrophil recruitment to the lung. A better understanding of the isoform‐specific and cell type–specific activities of PKD has the potential to lead to novel therapeutics for respiratory illnesses.
Development of white finger millet probiotic beverage using Lactocaseibacillus rhamnosus (LGG): Process optimization and study of physicochemical and nutritional properties
Authors: Navyashree Narayanaswamy , Buvaneswaran Malini , Sunil Chikkaballapur Krishnappa , Rawson Ashish , Natarajan Venkatachalapathy
Published: November 2022

White finger millet (WFM) is a repository of vital nutrients and minerals. This study aims to develop the white finger probiotic beverage, optimize the ingredients level for the formulation, and study the physiochemical and nutritional properties of the formulated vegan WFM probiotic beverage (WFMPB). The optimum condition for the development of WFMPB was obtained by Box–Behnken design. The independent variable like WFM flour (10–14% w/v), microbial inoculum (1–5% v/v), and sugar (5–15% w/v), and their impact on the response variables like total solid content (TSS), pH, microbial count, and viscosity were studied for optimization. Increment in the amounts of WFM flour and inoculum levels had a significant impact on the microbial load and pH. However, sugar levels affected viscosity and TSS. The combination of 14% WFM, 1% microbial inoculum, and 5% sugar showed maximum desirability of 0.975, with the highest sensory score (8.34), TSS of 15.4 °Brix, pH of 4.33, the microbial load of 9.45 log (cfu/ml) and viscosity of 43.32 cP. WFMPB consists of 11.91% carbohydrates, 1.46% protein, 0.89% fat, and 0.632% crude fiber. The rheological studies showed that WFMPB is a shear‐thinning fluid (n ˂ 0.1). The study revealed that WFM is the better carrier matrix for the LGG growth and can be an alternative for the strict vegan and lactose‐intolerant consumers.
Geothermometric constraints on the thermal architecture, metamorphism, and exhumation of the Northern Range, Trinidad
Authors: Gennaro Ivano , Weber John , Vitale Brovarone Alberto , Arkle Jeanette , Chu Xu
Published: November 2022

The Northern Range of Trinidad is composed of Mesozoic passive margin sedimentary rocks that underwent ductile deformation and subgreenschist‐ to greenschist‐facies metamorphism in the early Miocene. Previous studies suggested a two‐stage formation of the Northern Range between the Caribbean and South American plates: an initial collision drove mountain building in the Miocene and subsequent strike‐slip plate motion preferentially exhumed the western segment, producing a westward increase in the metamorphic thermal gradient. However, these studies were not able to resolve whether this gradient was discrete or continuous so the tectonic model awaits testing. In this study we use Raman spectroscopy on carbonaceous material (RSCM), an empirical geothermometer, to constrain peak temperatures across the Northern Range with a greater resolution than was available in previous studies. The RSCM temperatures show an abrupt increase from 337°C ± 10°C in the east to 442°C ± 16°C west of Chupara Point, where a range‐cutting fault (Chupara Fault) had been inferred in previous geologic mapping campaigns. Thus, the discrete thermal discontinuity of ~100°C very likely represents the Chupara Fault. Our RSCM‐derived peak metamorphic temperatures are 50°C to 100°C higher than those from previous estimates, requiring revision of tectonic models to account for deeper burial and greater exhumation. The peak metamorphic conditions determined here, and the deduced timing of faulting from published thermochronological data, are consistent with the two‐stage tectonic model proposed in previous studies.
Prevalence of nutrition risk and associated risk factors among New Zealand pre‐school children
Authors: Ross Helen , Kruger Rozanne , Wham Carol
Published: November 2022

Aim

To determine the prevalence of nutrition risk using the validated, Nutrition Screening Tool for Every Pre‐schooler (NutriSTEP) among pre‐school children in New Zealand (NZ) and to identify socio‐demographic factors associated with nutrition risk.

Methods

Parents/caregivers of NZ pre‐school children (aged 2–5 years) completed an online survey including NutriSTEP, both parent and child height and weight, as well as socio‐demographic characteristics. The 17‐item NutriSTEP responses were scored between 0 and 4; where item scores ≥2 indicate risk, and the maximum score is 68. Participants were stratified into low‐risk (score ≤ 20) and moderate to high‐risk (score > 20) groups. Strength of associations between nutrition risk and socio‐demographic characteristics were explored using binary regression analysis.

Results

Of 505 pre‐school children, 96 (19%) were at moderate to high risk (median interquartile range NutriSTEP score 24 [22–26]) and 409 (81%) were at low risk (score 13 [10–16]). Pre‐school children at highest risk were non‐NZ European (P = 0.002), with solo parents (P = 0.002), from households with incomes ≤$50 000 (P ≤ 0.021) and with non‐university educated parents (P ≤ 0.0001). More than 30% of pre‐schoolers were at high risk for inadequate consumption of fruit, vegetables, grains, milk products, meat and meat alternatives, as well as exposure to screens during meals and overuse of supplements.

Conclusions

A fifth of NZ pre‐school children were at moderate to high nutrition risk and may not have met the nutrition guidelines. Economic and ethnic disparities were apparent. Using NutriSTEP may assist to identify NZ pre‐school children at highest nutrition risk who may benefit from appropriate nutrition support.
Relative prevalence and outcome of fetal posterior fossa abnormality
Authors: Garg Nikita , Kumar Manisha , Rai Preeti , Srivastava Shivangi Shanker , Gupta Amit , Roy Chaudhary Subhasis
Published: November 2022

Aim

To find out the relative incidence and outcome of posterior fossa abnormality (PFA) in terms of survival at birth until 2 years of age.

Methods

We conducted a prospective study; all fetuses diagnosed with posterior fossa abnormality were followed‐up. The outcome was observed with respect to survival, the presence of associated anomalies, the existence of developmental delay after a telephonic interview.

Results

Out of 2703 children with congenital anomalies, 921 (34.1%) had a central nervous system defect; 76 cases of PFA were fully followed. Dandy–Walker malformation (DWM) was present in 50% (38/76), mega cisterna magna 18.4% (14/76), Blake pouch cyst 13.2% (10/76), vermian hypoplasia (VH) 13.2% (10/76) and arachnoid cyst 5.2% (4/76). The diagnosis was possible before 20 weeks in only 12 (15.8%) cases. The mean gestational age at delivery was 34.7 ± 6.7 weeks. Associated anomalies were seen in 35/76 (46.1%) cases. A total of 35/76 (46.1%) survived after 2 years; there was developmental delay in 9.2% of cases.

Conclusion

There is a large variation in the outcome of PFA depending upon the type of anomaly. Associated anomalies are common in VH and DWM, making their prognosis worse.
Owner preference for insulin delivery device and glycaemic control in diabetic dogs
Authors: Del Baldo F. , Colajanni L. , Corradini S. , Palagiano P. , Di Cunzolo A. , Perissinotto L. , Drudi I. , Horspool L. , Fracassi F.
Published: November 2022

Objectives

To assess treatment satisfaction and owner preference for two delivery devices (VetPen, MSD Animal Health, and U40 insulin syringes) and the effect on glycaemic control in diabetic dogs treated with porcine insulin zinc suspension.

Materials and Methods

Randomised prospective cross‐over study with two arms, each of 8 weeks. Twenty client‐owned diabetic dogs on insulin treatment by U40 syringe were enrolled. Dogs were randomly assigned to receive insulin by syringe or pen injector for 2 months, followed by 2 months of the other injection method. Treatment satisfaction and owners' insulin delivery device preference were assessed using a questionnaire. Glycaemic control was assessed using a clinical score, serum fructosamine and glycated haemoglobin (HbA1c%) at the time of the enrolment (T0) and the end of each arm of treatment (T2 and T4).

Results

Treatment satisfaction differed for the two types of the delivery device when the order that each device was used was taken into consideration. Owners who used the syringe first did not have a significant preference for an injection device. In contrast, owners who used the pen injector first expressed a significant preference for VetPen compared to syringes. No significant differences in the number of dogs of Groups 1 and 2 with good and poor glycaemic control at T2 and T4 were detected.

Clinical Significance

Overall treatment satisfaction and preference for the two delivery methods were similar. However, VetPen was preferred by owners who were randomised to use this device first. Glycaemic control did not appear to be affected by the insulin delivery device used.
Urban forest soils harbour distinct and more diverse communities of bacteria and fungi compared to less disturbed forest soils
Authors: Scholier Tiffany , Lavrinienko Anton , Brila Ilze , Tukalenko Eugene , Hindström Rasmus , Vasylenko Andrii , Cayol Claire , Ecke Frauke , Singh Navinder J. , Forsman Jukka T. , Tolvanen Anne , Matala Juho , Huitu Otso , Kallio Eva R. , Koskela Esa , Mappes Tapio , Watts Phillip C.
Published: November 2022

Anthropogenic changes to land use drive concomitant changes in biodiversity, including that of the soil microbiota. However, it is not clear how increasing intensity of human disturbance is reflected in the soil microbial communities. To address this issue, we used amplicon sequencing to quantify the microbiota (bacteria and fungi) in the soil of forests (n = 312) experiencing four different land uses, national parks (set aside for nature conservation), managed (for forestry purposes), suburban (on the border of an urban area) and urban (fully within a town or city), which broadly represent a gradient of anthropogenic disturbance. Alpha diversity of bacteria and fungi increased with increasing levels of anthropogenic disturbance, and was thus highest in urban forest soils and lowest in the national parks. The forest soil microbial communities were structured according to the level of anthropogenic disturbance, with a clear urban signature evident in both bacteria and fungi. Despite notable differences in community composition, there was little change in the predicted functional traits of urban bacteria. By contrast, urban soils exhibited a marked loss of ectomycorrhizal fungi. Soil pH was positively correlated with the level of disturbance, and thus was the strongest predictor of variation in alpha and beta diversity of forest soil communities, indicating a role of soil alkalinity in structuring urban soil microbial communities. Hence, our study shows how the properties of urban forest soils promote an increase in microbial diversity and a change in forest soil microbiota composition.
Weekly line planning to improve the match between rail supply and passenger demand
Authors: Nie Bowen , Nie Lei , Fu Huiling , Wu Xin
Published: November 2022

Traditional railway line planning approaches are used to determine the best train lines during specified periods (e.g., 1 day, 1 h, or several hours). However, mismatches occur relative to the spatiotemporal changes in travel demands over longer time periods (e.g., 1 week). To more effectively match rail supply with passenger demand, a weekly line planning (WLP) model considering both peak and nonpeak passenger demand over an entire week and during all periods of each day is proposed. This model maximizes the defined supply–demand matching utility and minimizes train operational cost. Important constraints to ensure proper daily and hourly train repetition over multiple days are included. A customized genetic algorithm (GA) is developed, which outperforms the CPLEX solver in real‐world cases of high‐speed railways in China. Compared with practical and single‐day planning, WLP shows clear improvement in terms of operational cost, passenger travel speed, and supply–demand matching.
Modeling adult COX‐2 cerebrospinal fluid pharmacokinetics to inform pediatric investigation
Authors: Hannam Jacqueline A. , Murto Kimmo T. , Anderson Brian J. , Dembo Gregory , Kharasch Evan D.
Published: November 2022

Aim

Hysteresis is reported between plasma concentration and analgesic effect from nonsteroidal anti‐inflammatory drugs. It is possible that the temporal delay between plasma and CSF nonsteroidal anti‐inflammatory drugs mirrors this hysteresis. The temporal relationship between plasma and CSF concentrations of COX‐inhibitors (celecoxib, rofecoxib, valdecoxib) has been described. The purpose of this secondary data analysis was to develop a compartmental model for plasma and CSF disposition of these COX‐2 inhibitors.

Methods

Plasma and CSF concentration‐time profiles and protein binding data in 10 adult volunteers given oral celecoxib 200 mg, valdecoxib 40 mg and rofecoxib 50 mg were available for study. Nonlinear mixed effects models with a single plasma compartment were used to link a single CSF compartment with a transfer factor and an equilibration rate constant (Keq). To enable predictive modeling in pediatrics, celecoxib pharmacokinetics were standardized using allometry.

Results

Movement of all three unbound plasma COX‐2 drugs into CSF was characterized by a common equilibration half‐time (T1/2keq) of 0.84 h. Influx was faster than efflux and a transfer scaling factor of 2.01 was required to describe conditions at steady‐state. Estimated celecoxib clearance was 49 (95% CI 34–80) L/h/70 kg and the volume of distribution was 346 (95% CI 237–468) L/70 kg. The celecoxib absorption half‐time was 0.35 h with a lag time of 0.62 h. Simulations predicted a 70‐kg adult given oral celecoxib 200 mg with maintenance 100 mg twice daily would have a mean steady‐state total (bound and unbound) plasma concentration of 174 μg L−1 and CSF concentration of 1.1 μg L−1. A child (e.g., 25 kg, typically 7 years) given oral celecoxib 6 mg kg−1 with maintenance of 3 mg kg−1 twice daily would have 282 and 1.7 μg L−1 mean plasma and CSF concentrations, respectively.

Conclusions

Transfer of unbound COX‐2 inhibitors from plasma to CSF compartment can be described with a delayed effect model using an equilibration rate constant to collapse observed hysteresis. An additional transfer factor was required to account for passage across the blood–brain barrier. Use of a target concentration strategy for dose and consequent plasma (total and unbound) and CSF concentration prediction could be used to inform pediatric clinical studies.
Who are pure exporters?
Authors: Mahakitsiri Doungdao , Suwanprasert Wisarut
Published: November 2022

The existing literature establishes the pattern that exporters in developed countries sell most of their output in their own domestic markets; however, recent evidence suggests that the export intensity distributions of 47 countries exhibit peaks at each end. In this study, we study the characteristics of pure exporters, namely exporters at the right‐hand peak of the distribution. We use Thailand's firm‐level panel data covering the period from 2007 through 2017 to estimate factors that explain the likelihood that a firm self‐selects to be a pure exporter. We do not find evidence that firm‐level productivity can explain the decision to become a pure exporter. Rather, the main factors that determine the decision are the capital–labour ratio, the amount of labour, foreign ownership, investment promotion and firm age.
Emission reduction and value‐added export nexus at firm level
Authors: Deng Yuping , Wu Yanrui , Xu Helian
Published: November 2022

This paper aims to investigate the effects of the share of domestic value added in exports on firm‐level emission intensity in China. It shows that the ratio of domestic value added in exports is negatively associated with firms' emission discharges. This relation is more profound for firms in ordinary trade than those in processing trade. Further analysis illustrates that the observed relationship is especially prevalent in eastern regions, technology‐intensive industries and non‐state‐owned firms.
An automated method for detecting F measurement jumps based on sample-to-sample differences
Authors: Steffman Jeremy , Cole Jennifer
Published: November 2022

An algorithm for detecting sudden jumps in measured F0, which are likely to be inaccurate measures, is introduced. The method computes sample-to-sample differences in F0 and, based on a user-defined threshold, determines whether a difference is larger than naturally produced F0 velocities, thus, flagging it as an error. Various parameter settings are evaluated on a corpus of 30 American English speakers producing different intonational patterns, for which F0 tracking errors were manually checked. The paper concludes in recommending settings for the algorithm and ways in which it can be used to facilitate analyses of F0 in speech research.
Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection
Authors: Jiang Tiemin , Sun Wujianan , Aji Tuerganaili , Shao Yingmei , Guo Chuang , Zhang Chuanshan , Ran Bo , Hou Jiao , Yasen Aimaiti , Guo Qiang , Wang Hui , Qu Kun , Wen Hao
Published: November 2022

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an “immunosuppressive” microenvironment are poorly understood.
PBP1A Directly Interacts with the Divisome Complex to Promote Septal Peptidoglycan Synthesis in Acinetobacter baumannii
Authors: Kang Katie N. , Boll Joseph M.
Published: November 2022

Peptidoglycan biosynthesis is a validated target of β-lactam antibiotics, and it is critical that we understand essential processes in multidrug-resistant pathogens such as
Acinetobacter baumannii
. While model systems such as
Escherichia coli
have shown that PBP1A is associated with side wall peptidoglycan synthesis, we show herein that
A. baumannii
PBP1A directly interacts with the divisome component PBP3 to promote division, suggesting a unique role for the enzyme in this highly drug-resistant nosocomial pathogen.
A. baumannii
demonstrated unanticipated resistance and tolerance to envelope-targeting antibiotics, which may be driven by rewired peptidoglycan machinery and may underlie therapeutic failure during antibiotic treatment.
NtrC Increases Fitness of Salmonella enterica Serovar Typhimurium under Low and Fluctuating Nutrient Conditions
Authors: Mishra L. K. , Shashidhar R.
Published: November 2022

S.
Typhimurium, both in host and external environment, faces enormous competition from other microorganisms.
Activation of the Chemokine Receptor CCR1 and Preferential Recruitment of Gαi Suppress RSV Replication: Implications for Developing Novel Respiratory Syncytial Virus Treatment Strategies
Authors: Li Jiao , Xue Ling , Wang Jiachao , Meng Aihong , Qiao Jiajun , Li Miao , Wang Xiuli , Meng Lingtong , Ning Jingyuan , Gao Xue , Li Wenjian , Ma Cuiqing , Wei Lin
Published: November 2022

Our results revealed a novel mechanism by which RSV escapes innate immunity. That is, although it induces high CCL5 expression, RSV might attenuate the binding of CCL5 by downregulating the expression of CCR1 in respiratory epithelial cells to weaken the inhibitory effect of CCR1 on HSP90 activity and thereby facilitate RSV replication in nonimmune cells.
Draft Genome Sequence of the Protozoan Parasite Leishmania braziliensis Strain BA788, Isolated from a Clinical Case in Bahia State, Brazil
Authors: Coqueiro-dos-Santos Anderson , Bento Gabrielle Ariadine , Barral Aldina , de Oliveira Camila I. , Bartholomeu Daniella C.
Published: November 2022

The draft genome of the parasite
Leishmania braziliensis
strain BA788, which was isolated from a patient from Bahia state, Brazil, was sequenced using Illumina paired-end technology. The assembled genome is 33.5 Mb long and contains 7,603 genes. This genome will contribute to studies aimed at understanding the pathogenesis caused by this parasite strain.
Pixantrone Sensitizes Gram-Negative Pathogens to Rifampin
Authors: She Pengfei , Li Zehao , Li Yimin , Liu Shasha , Li Linhui , Yang Yifan , Zhou Linying , Wu Yong
Published: November 2022

Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health.
Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives
Authors: Hatmaker E. Anne , Rangel-Grimaldo Manuel , Raja Huzefa A. , Pourhadi Hadi , Knowles Sonja L. , Fuller Kevin , Adams Emily M. , Lightfoot Jorge D. , Bastos Rafael W. , Goldman Gustavo H. , Oberlies Nicholas H. , Rokas Antonis
Published: November 2022

Aspergillus flavus
is a filamentous fungus that causes opportunistic human infections, such as aspergillosis and fungal keratitis, but its close relatives are considered nonpathogenic. To begin understanding how this difference in pathogenicity evolved, we characterized variation in infection-relevant genomic, chemical, and phenotypic traits between strains of
A. flavus
and its relatives.
Pan-Genome Analysis of Staphylococcus aureus Reveals Key Factors Influencing Genomic Plasticity
Authors: Liu Na , Liu Danping , Li Kexin , Hu Songnian , He Zilong
Published: November 2022

We sought to explore the impact of driving factors influencing pan-genome composition using
Staphylococcus aureus
as a model organism to provide new insights for the study of bacterial pan-genomes. We believe that the sequence type (ST) of the strains under consideration plays a significant role in the dynamic distribution of bacterial genes.
Barriers and facilitators to HIV and syphilis rapid diagnostic testing in antenatal care settings in low-income and middle-income countries: a systematic review
Authors: Zhang Ye , Guy Rebecca , Camara Hawa , Applegate Tanya L , Wiseman Virginia , Treloar Carla , Lafferty Lise
Published: November 2022

Background

Testing and treatment during pregnancy is a well-established and cost-effective prevention strategy, which relies largely on use of rapid diagnostic tests (RDTs). Yet, in many low-income and-middle-income countries, the uptake of RDTs is suboptimal. A qualitative meta-synthesis was conducted to identify the barriers and enablers to use of HIV and syphilis RDTs among pregnant women in low-income and middle-income countries.

Methods

This review was conducted using PRISMA guidelines. Eligible studies included peer-reviewed publications, which used qualitative methods to explore HIV and syphilis RDT in antenatal care clinics in low-income and middle-income countries. Studies focusing on perspectives of pregnant women, healthcare workers and/or stakeholders were included. We used an inductive approach informed by a modified socioecological model to synthesise the data.

Results

62 manuscripts met the eligibility criteria. For pregnant women, initial acceptance of the RDT and continuation in antenatal care depends on the perception that engaging in testing will be a beneficial experience for their baby and themselves, often influenced by the provision of services that are gender-sensitive, confidential, respectful, flexible and considers their well-being into the future. Local sociocultural beliefs about pregnancy and diseases, awareness of diseases and gender roles in society also influenced RDT acceptability among pregnant women. For healthcare workers, the ability to provide high-quality RDT care required ongoing training, accurate and easy to use tests, support from supervisors and communities, sufficient resources and staffing to provide services, and reliable salary. At the stakeholder level, well-developed guidelines and health system infrastructures were imperative to the delivery of RDT in antenatal clinics.

Conclusion

Our findings highlight clear gaps to the provision of sustainable and culturally acceptable maternal HIV and/or syphilis screening using RDTs. In addition, greater attention needs to be paid to community stakeholders in promoting the uptake of RDT in antenatal clinics.

PROSPERO registration number

CRD42018112190.
School readiness among children born to women living with HIV in Dar es Salaam, Tanzania: a cohort study protocol
Authors: Perumal Nandita , Saleh Arvin , Muhihi Alfa , McCoy Dana , Seiden Jonathan , Bakari Mohamed , Ndesangia Veneranda , Ulenga Nzovu , Sudfeld Christopher R , Manji Karim P
Published: November 2022

Introduction

Children who are born to women living with HIV are at a greater risk of suboptimal neurodevelopment; however, evidence from sub-Saharan Africa is limited and functional developmental outcomes are rarely assessed in this vulnerable population. The School Readiness among HIV-Exposed Children (SRHEC) cohort study aims to assess the school readiness of preschool aged children born to women living with HIV and to identify the biological, environmental and social factors that contribute to school readiness in this population.

Methods and analysis

The SRHEC cohort is an observational follow-up study of children born to HIV-infected pregnant women who were previously enrolled in a maternal vitamin D supplementation randomised, placebo-controlled trial in Dar es Salaam, Tanzania. This parent trial enrolled 2300 pregnant women and followed mothers and infants up to 1-year postpartum. Mother/caregiver and child pairs will be eligible for the SRHEC follow-up study if the child is between 3 and 6.5 years of age at assessment, and the mother/caregiver provides informed consent. The International Development and Early Learning Assessment tool will be used to assess children’s school readiness, including their early literacy, early numeracy, motor, socialemotional, and executive function skills. Data on maternal and child health and nutritional status (eg, anthropometry, blood pressure and diet) will be collected using standardised instruments and survey-based questionnaires. Data on maternal/caregiver depression and anxiety, maternal exposure to intimate partner violence, and HIV-related stigma will also be collected. Generalised linear and logistic regressions will be used to assess the relationship between child school readiness and biological, social, environmental factors.

Ethics and dissemination

This study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University of Health and Allied Sciences, and the Harvard T.H. Chan School of Public Health. We will disseminate our results in the form of scientific conference presentations and peer-reviewed publications.
Characterizations of Hyperideals and Interior Hyperideals in Ordered
Γ
-Semihypergroups
Authors: Rao Yongsheng , Zhou Qixin , Cai Ruiqi , Khan Aysha
Published: November 2022

We give some conditions on ordered

Γ

-semihypergroups under which their interior hyperideal is equal to the hyperideal. In this paper, it is shown that in regular (resp., intraregular, semisimple) ordered

Γ

-semihypergroups, the hyperideals and the interior hyperideals coincide. To show the importance of these results, some examples and conclusions are provided.
Development of Green UV-Vis Method for Direct Determination of Total Sugars in the Aqueous Extract of Teff (Eragrostis tef (Zuccagni) Trotter) Grains and Other Cereals
Authors: Yisak Hagos , Tukue Hagos , Redi-Abshiro Mesfin , Chandravanshi Bhagwan Singh , Yaya Estifanos Ele
Published: November 2022

There is no ultraviolet visible (UV-Vis) spectrophotometric method for the direct determination of total sugars in the aqueous extract of teff grain samples. Therefore, the objective of this study was to develop a green UV-Vis spectrophotometric method to determine total sugars in the aqueous extract of white teff, brown teff, white rice, and red wheat grain samples. The calibration curve was established in the range of 20.11–7,907 mg/L using sucrose as a standard with R2 = 0.9996. The limit of detection and limit of quantification were 4.4 and 14.6 mg/L, respectively. The relative standard deviation (6.9%) of the method for the sucrose standard was within the acceptable range indicating that the method is precise. The amount of total sugars determined in the white teff (5.48–9.44% (w/w), brown teff (6.17–10.32% (w/w)), white rice (3.19% (w/w)), and red wheat (9.22% (w/w)) grain samples was comparable with other reported cereal grains. Furthermore, the accuracy of the developed analytical method was also evaluated by spiking the known amount of the sucrose standard solution to the white teff, brown teff, white rice, and red wheat sample extracts, and percentage recoveries found were in the acceptable range (85 ± 2 − 105 ± 4%) with an average recovery of 93%, confirming that the new green method is quantitatively reproducible. Hence, a fast, simple, inexpensive, widely used, selective, sensitive, precise, and accurate green UV-Vis method was developed and validated for the direct determination of total sugars in the aqueous extract of teff, white rice, and red wheat grain samples.
IsoqurPEKS: An Isogeny-Based Quantum-Resistant Public-Key Encryption Scheme with Keyword Search
Authors: Fan Qing , Luo Min , Peng Cong , Wang Lianhai , He Debiao
Published: November 2022

Since the convenience and advancement of cloud applications, many users (e.g., companies or individuals) adopt remote cloud services to reduce the local storage overload and computing consumption. However, before transferring them to the cloud server, users always encrypt outsourced data for the privacy of important data, which deprives flexible usage of these data. Public key encryption with keyword search (PEKS) undoubtedly offers a precise resolution to this issue. Unfortunately, most PEKS schemes cannot fight against quantum computing attackers, which is increasingly a research hotspot. To achieve postquantum security and privacy-preserving search function, we propose a quantum-resistant PEKS scheme named IsoqurPEKS. Our proposed instantiation satisfies basic semantic security indistinguishable against chosen keyword attack (IND-CKA), and IsoqurPEKS is proved to be secure under the security model. Furthermore, we compare IsoqurPEKS with the other eight current PEKS schemes with respect to security properties, communication, and computation costs. The comparison results indicate that the proposed scheme has the best security and performance among the nine PEKS schemes.
Inhibitory Effects of Parachlorella Beijerinckii Extracts on the Formation of Advanced Glycation End Products and Glycative Stress-Induced Inflammation in an In Vitro Skin Dermis-Like Model
Authors: Imai Yumi , Nakashima Yuya , Kanno Toshihiro
Published: November 2022

Advanced glycation end products (AGEs) are formed via a nonenzymatic glycosylation reaction called glycation. The formation and accumulation of AGEs increases in skin with age, contributing to the appearance of facial wrinkles and loss of skin elasticity. Therefore, inhibition of AGEs may delay skin aging. The microalgae Parachlorella beijerinckii has been used as a health food supplement for many years and contains carotenoids and vitamins that have antioxidant and anti-inflammatory effects. The aim of this study was to investigate whether Chlorella extract also has antiglycation activity. Antiglycation activity was measured using fluorescent AGEs, Nε-(carboxymethyl) lysine (CML), and Nε-(carboxymethyl) arginine (CMA) from glycated bovine serum albumin and type I collagen in vitro. A gel with a dermis-like structure consisting of collagen and a live fibroblast cell line was glycated with glyoxal. The content of fluorescent AGE, CML, and CMA, and the gel contraction activity were measured. In addition, to investigate the level of inflammation induced by the glycation of the collagen gel, the expression level of the receptor for AGEs and interleukin-8 were examined. Fat-solubleChlorella extract suppressed the formation of fluorescent AGEs, CML, and CMA in both models. These results indicated that Chlorella extract directly inhibited AGE formation. The collagen gel contracted over time during culturing, whereas contraction was inhibited in the glyoxal-treated collagen gel. Chlorella extract remarkably attenuated the glyoxal-induced gel contraction. Moreover, Chlorella extract substantially decreased the fluorescent AGEs, CML, and CMA in the collagen gels with glyoxal. Glyoxal exposure increased the expression levels of interleukin-8 and receptor for AGE proteins in collagen gels, while Chlorella extract inhibited this increase. This study showed that fat-solubleChlorella extract has a direct inhibitory effect on AGEs and decreases receptor expression for AGE-mediated inflammation by reducing AGEs. Chlorella may delay skin aging by inhibiting the formation and accumulation of AGEs.
ATF3 Reprograms the Bone Marrow Niche in Response to Early Breast Cancer Transformation
Authors: Perrone Milena , Chiodoni Claudia , Lecchi Mara , Botti Laura , Bassani Barbara , Piva Annamaria , Jachetti Elena , Milani Matteo , Lecis Daniele , Tagliabue Elda , Verderio Paolo , Sangaletti Sabina , Colombo Mario P.
Published: November 2022

Cancer is a systemic disease able to reprogram the bone marrow (BM) niche towards a protumorigenic state. The impact of cancer on specific BM subpopulations can qualitatively differ according to the signals released by the tumor, which can vary on the basis of the tissue of origin. Using a spontaneous model of mammary carcinoma, we identified BM mesenchymal stem cells (MSC) as the first sensors of distal cancer cells and key mediators of BM reprogramming. Through the release of IL1B, BM MSCs induced transcriptional upregulation and nuclear translocation of the activating transcription factor 3 (ATF3) in hematopoietic stem cells. ATF3 in turn promoted the formation of myeloid progenitor clusters and sustained myeloid cell differentiation. Deletion of Atf3 specifically in the myeloid compartment reduced circulating monocytes and blocked their differentiation into tumor-associated macrophages. In the peripheral blood, the association of ATF3 expression in CD14+ mononuclear cells with the expansion CD11b+ population was able to discriminate between women with malignant or benign conditions at early diagnosis. Overall, this study identifies the IL1B/ATF3 signaling pathway in the BM as a functional step toward the establishment of a tumor-promoting emergency myelopoiesis, suggesting that ATF3 could be tested in a clinical setting as a circulating marker of early transformation and offering the rationale for testing the therapeutic benefits of IL1B inhibition in patients with breast cancer.

Significance: Bone marrow mesenchymal stem cells respond to early breast tumorigenesis by upregulating IL1B to promote ATF3 expression in hematopoietic stem cells and to induce myeloid cell differentiation that supports tumor development.
Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma
Authors: Jiang Haowen , Greathouse Rachel L. , Tiche Sarah Jane , Zhao Man , He Bo , Li Yang , Li Albert M. , Forgo Balint , Yip Michaela , Li Allison , Shih Moriah , Banuelos Selene , Zhou Meng-Ning , Gruber Joshua J. , Rankin Erinn B. , Hu Zhen , Shimada Hiroyuki , Chiu Bill , Ye Jiangbin
Published: November 2022

The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer. In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), to activate mitochondrial respiration, which induced neural differentiation in neuroblastoma cells. NEN treatment increased the NAD+/NADH and pyruvate/lactate ratios and also the α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, NEN treatment induced promoter CpG island demethylation and epigenetic landscape remodeling, activating the neural differentiation program. In addition, NEN treatment upregulated p53 but downregulated N-Myc and β-catenin signaling in neuroblastoma cells. Importantly, even under hypoxia, NEN treatment remained effective in inhibiting 2-HG generation, promoting DNA demethylation, and suppressing hypoxia-inducible factor signaling. Dietary NEN intervention reduced tumor growth rate, 2-HG levels, and expression of N-Myc and β-catenin in tumors in an orthotopic neuroblastoma mouse model. Integrative analysis indicated that NEN treatment upregulated favorable prognosis genes and downregulated unfavorable prognosis genes, which were defined using multiple neuroblastoma patient datasets. Altogether, these results suggest that mitochondrial uncoupling is an effective metabolic and epigenetic therapy for reversing the Warburg effect and inducing differentiation in neuroblastoma.

Significance:

Targeting cancer metabolism using the mitochondrial uncoupler niclosamide ethanolamine leads to methylome reprogramming and differentiation in neuroblastoma, providing a therapeutic opportunity to reverse the Warburg effect and suppress tumor growth.

See related commentary by Byrne and Bell, p.167
DOT1 L Regulates Ovarian Cancer Stem Cells by Activating β-catenin Signaling
Authors: Zhang Yaqi , Wang Yinu , Valdivia Andres , Huang Hao , Matei Daniela
Published: November 2022

Cancer stem cells (CSC) represent a population of cancer cells responsible for tumor initiation, chemoresistance, and metastasis. Here, we identified the H3K79 methyltransferase disruptor of telomeric silencing-1–like (DOT1L) as a critical regulator of self-renewal and tumor initiation in ovarian CSCs. DOT1 L was upregulated in ovarian CSCs versus non-CSCs. shRNA-mediated DOT1 L knockdown decreased the aldehyde dehydrogenase (ALDH)+ cell population, impaired the tumor initiation capacity (TIC) of ovarian CSCs, and blocked the expression of stemness-associated genes. Inhibition of DOT1L's methyltransferase activity by the small-molecule inhibitor (DOT1Li) EPZ-5676 also effectively targeted ovarian CSCs. Integrated RNA-sequencing analyses of ovarian cancer cells in which DOT1 L was knocked down versus control cells and of ovarian CSCs versus non-CSCs, identified Wnt signaling as a shared pathway deregulated in both CSCs and in DOT1L-deficient ovarian cancer cells. β-catenin, a key transcription factor regulated by Wnt, was downregulated in ovarian cancer cells in which DOT1 L was knocked down and upregulated in DOT1 L overexpressing ovarian cancer cells. Chromatin immunoprecipitation (ChIP) revealed enrichment of the H3K79Me3 mark at the β-catenin promoter, suggesting that its transcription is regulated by DOT1L. Our results suggest that DOT1 L is critical for the self-renewal and TIC of ovarian CSCs by regulating β-catenin signaling. Targeting DOT1 L in ovarian cancer could be a new strategy to eliminate CSCs.

Implications:

This study found that the histone methyltransferase DOT1 L regulates the self-renewal and tumor initiation capacity of ovarian CSCs and suggests DOT1 L as a new cancer target.