bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and dynamic investigation of non‐synonymous variations in Renin–AGT complex revealed altered binding via hydrogen‐bonding network reprogramming to accelerate the hypertension pathway
Authors: Ahmad Hussain , Khan Abbas , Umbreen Shaheena , Khan Taimoor , Xuewei Zheng , Wei Dong‐Qing , Tian Zhongmin
Published: June 2022

Hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. Angiotensinogen and renin are key components of the renin–angiotensin–aldosterone system, which plays an indispensable role in hypertension. The aim of this study was to find out the non‐synonymous mutations and structure‐based mutation‐function correlation in the renin–AGT complex and reveal the most deleterious mutations to accelerated hypertension. In the current study, we employed computational modeling and molecular simulation approaches to demonstrate the impact of specific mutations in the REN‐AGT interface in hypertension. Computational algorithms, that is, PhD‐SNP, PolyPhen‐1, MAPP, Sorting Intolerant from Tolerant, Screening of non‐acceptable polymorphism, PredictSNP, PolyPhen‐2, and Protein Analysis Through Evolutionary Relationships predicted 20 mutations as deleterious in AGT while only five mutations were confirmed as deleterious in the renin protein. Investigation of the bonding analysis revealed that two mutations S107L and V193F in renin altered the hydrogen‐bonding paradigm at the interface site. Furthermore, exploration of structural‐dynamic behaviors demonstrated by that these mutations also increases the structural stability to regulate the expression of disease pathway. The flexibility index of each residues and structural compactness analysis further validated the findings by portraying the difference in the dynamic behavior in contrast to the wild type. Binding energy calculations based on molecular mechanics/generalized Born surface area methods were used which further established the binding differences between the wild type, S107L, and V193F mutant variants. The total binding energy for wild type, S107L, and V193F was reported to be −27.79, −47.72, and −38.25, respectively. In conclusion, these two mutations increase the binding free energy alongside the docking score to enhance the binding between renin and AGT to overexpress this pathway in a hypertension disease condition. Patients with these mutations may be screened for potential therapeutic intervention.
Model‐informed drug development for immuno‐oncology agonistic anti‐GITR antibody GWN323: Dose selection based on MABEL and biologically active dose
Authors: Ji Yan , Knee Deborah , Chen Xinhui , Dang Anhthu , Mataraza Jennifer , Wolf Babette , Sy Sherwin K. B.
Published: June 2022

GWN323, an agonistic human anti‐GITR (glucocorticoid‐induced TNFR‐related protein) IgG1 antibody, was studied clinically as an immuno‐oncology therapeutic agent. A model‐based minimum anticipated biological effect level (MABEL) approach integrating in vitro and in vivo data informed dose selection for the first‐in‐human (FIH) study. Data evaluated included pharmacokinetics (PK) of DTA‐1.mIgG2a (mouse surrogate GITR antibody for GWN323), target‐engagement pharmacodynamic (PD) marker soluble GITR (sGITR), tumor shrinkage in Colon26 syngeneic mice administered with DTA‐1.mIgG2a, cytokine release of GWN323 in human peripheral blood mononuclear cells, and GITR binding affinity. A PK model was developed to describe DTA‐1.mIgG2a PK, and its relationship with sGITR was also modeled. Human GWN323 PK was predicted by allometric scaling of mouse PK. Based on the totality of PK/PD modeling and in vitro and in vivo pharmacology and toxicology data, MABEL was estimated to be 3–10 mg once every 3 weeks (Q3W), which informed the starting dose selection of the FIH study. Based on tumor kinetic PK/PD modeling of tumor inhibition by DTA‐1.mIgG2a in Colon26 mice and the predicted human PK of GWN323, the biologically active dose of GWN323 was predicted to be 350 mg Q3W, which informed the dose escalation of the FIH study. GWN323 PK from the FIH study was described by a population PK model; the relationship with ex vivo interleukin‐2 release, a target‐engagement marker, was also modeled. The clinical PK/PD modeling data supported the biological active dose projected from the translational PK/PD modeling in a “learn and confirm” paradigm of model‐informed drug development of GWN323.
Effect of limited protein consumption during the larval and adult stage on life‐history traits of the Mexican fruit fly
Authors: González‐López Gonzalo Iván , Orozco‐Dávila Dina , López‐Hernández Patricia , Díaz‐Fleischer Francisco , Alvarado‐Castillo Gerardo , Sánchez‐Viveros Gabriela , Pérez‐Staples Diana
Published: June 2022

Anastrepha ludens Loew (Diptera: Tephritidae) is an important mango and citrus pest. The sterile insect technique (SIT) is currently used to control this fly. The SIT involves the release of sterile insects to reduce wild populations through the induction of sterility. Prior to release, insects are mass‐reared on artificial diets. The rearing of A. ludens involves the provision of protein both in the larval and adult stage, thus we studied trade‐offs between larval and adult diets. We compared various yeast concentrations in the larval diet and two formulations in the adult diet, both at small and semi‐mass scale. We determined the quality of the insects at all developmental stages. Low concentrations of torula yeast (TY) (2.9 and 3.6%) produced larvae and pupae of low weight, fewer larvae and pupae, and more males than higher TY concentrations (6.1%), but this was only discernable at a small scale. Adult survival without water and food was significantly lower for non‐irradiated males and females, and irradiated males when reared on 6.1% TY. For mating success, we found that non‐irradiated males reared on 4.8% TY but fed only sugar (S) as adults had lower probability of mating than males fed yeast hydrolysate (YH). For irradiated males, larval diet had no effect on mating competitiveness, only males fed with S + YH in the adult diet had higher mating success than those fed with S only. We propose reducing TY in the larval diet to 5.1%; however, for release colonies S + YH will need to be provided in the adult diet. Knowledge on larval and adult nutritional requirements will aid in our understanding of insect nutritional ecology and will also improve mass‐rearing diets.
Bonding over a death: signalling in the funeral episode of Ibn Faḍlān’s Risala
Authors: Taggart Declan
Published: June 2022

Many of the rites described by Ibn Faḍlān in his account of a Rūs funeral remain obscure. Rather than attempting to further puzzle out the symbolic content of these funerary practices, this article uses signalling theory to examine their role in group dynamics. Signalling theory examines the honesty of communications between individuals, focusing especially on how costly acts can represent the fitness and cooperative qualities of the communicator. Applying this theory to Ibn Faḍlān’s descriptions can help elucidate the funeral’s impact on in‐group and out‐group observers, the transmission of associated counter‐intuitive beliefs and, more broadly, group fitness and prosociality.
Epilepsy research in Africa: A scoping review by the ILAE Pediatric Commission Research Advocacy Task Force
Authors: Samia Pauline , Hassell Jane , Hudson Jessica , Ahmed Azim , Shah Jasmit , Hammond Charles , Kija Edward , Auvin Stéphane , Wilmshurst Jo
Published: June 2022

Objective

Despite the high prevalence of epilepsy in Africa, evaluation of epilepsy research trends on the continent is lacking. Without establishing effective research, improvement in care for people with epilepsy cannot be effectively strategized or targeted.

Methods

A scoping review of the peer‐reviewed literature on epilepsy from Africa (1989–2019) was conducted. The aim was to understand from this what areas are well researched versus underresearched based on published epilepsy topics.

Results

A total of 1227 publications were identified and assessed. A significant increase in publications occurred over the 30 years assessed. African author leadership was evident in most reports. Nine countries had >50 publications identified; the remaining 45 countries had <50 or no publications. Research studies were typically of lower quality (case series and observational studies). Research themes were more focused on clinical epilepsy (descriptive observational studies) and social aspects (qualitative surveys). However, there were a number of unique and strong themes, specifically for neurocysticercosis and nodding syndrome, where strong research collaborations were evident, basic science understandings were explored, and interventional models were established.

Significance

Despite Africa being the continent with the most countries, it is lacking in the quantity, quality, and for some areas, relevance of research on epilepsy. Targeted approaches are needed to upskill the strength of research undertaken with more basic science, interventional, and randomized controlled studies. Themes of research need to promote those with unique African content but also to align with current international research areas that have impact on care delivery, such as epilepsy surgery and epilepsy genetics. For this to be possible, it is important to strengthen research hubs with collaborations that empower Africa to own its epilepsy research journey.
Immunomodulatory role of mitochondrial DAMPs: a missing link in pathology?
Authors: Garg Mayank , Johri Saumya , Chakraborty Krishnendu
Published: June 2022

In accordance with the endosymbiotic theory, mitochondrial components bear characteristic prokaryotic signatures, which act as immunomodulatory molecules when released into the extramitochondrial compartment. These endogenous immune triggers, called mitochondrial damage‐associated molecular patterns (mtDAMPs), have been implicated in the pathogenesis of various diseases, yet their role remains largely unexplored. In this review, we summarise the available literature on mtDAMPs in diseases, with a special focus on respiratory diseases. We highlight the need to bolster mtDAMP research using a multipronged approach, to study their effect on specific cell types, receptors and machinery in pathologies. We emphasise the lacunae in the current understanding of mtDAMPs, particularly in their cellular release and the chemical modifications they undergo. Finally, we conclude by proposing additional effects of mtDAMPs in diseases, specifically their role in modulating the immune system.
When in Rome: Local social norms and income differences
Authors: Burns Natasha , Keithley Andrew , Minnick Kristina , Rivolta Mia L.
Published: June 2022

We investigate whether social capital influences tournament incentives and income differences between the chief executive officer (CEO) and median worker. We find that firms headquartered in US counties with stronger norms of cooperation or social capital have lower tournament and income differences. Firm value is higher when compensation is consistent with local norms. The results hold for alternative measures of social capital, instrumental variables, and quasi‐experiments related to the legalization of marijuana and firm headquarter relocation. These findings suggest that local social norms influence income differences and firm performance.
Biomass, community composition and N:P recycling ratios of zooplankton in northern high‐latitude lakes with contrasting levels of N deposition and dissolved organic carbon
Authors: Bergström Ann‐Kristin , Lau Danny C. P. , Isles Peter D. F. , Jonsson Anders , Creed Irena F.
Published: June 2022

Global changes are causing decreases in inorganic nitrogen (N) concentrations, increases in coloured dissolved organic carbon (DOC) concentrations, and decreases in dissolved inorganic N to total phosphorus ratios (DIN:TP) in northern lakes. The effects of these changes on phytoplankton and zooplankton biomass and the N:P recycling ratio of zooplankton remain unresolved.

In 33 Swedish headwater lakes across subarctic‐to‐boreal gradients with different levels of N deposition (low N in the north [Västerbotten, boreal; Abisko, subarctic] vs. high N in the south [Värmland, boreal; Jämtland, subarctic]), we measured water chemistry, phytoplankton biomass (chlorophyll‐a [Chl‐a], Chl‐a:TP), seston mineral quality (C:P, N:P), as well as zooplankton biomass, community composition, and C:N:P stoichiometry. We estimated nutrient imbalances and the N:P recycling ratios of zooplankton using ecological stoichiometry models.

There was a large‐scale gradient from low lake DIN and DIN:TP in the north to high DIN and DIN:TP in the south, with lower DIN:TP in lakes coinciding with higher DOC within each region. Lower lake DIN was associated with lower phytoplankton biomass (lower Chl‐a:TP). Lower lake DIN:TP was associated with richer seston mineral quality (lower seston C:P and N:P) and higher zooplankton biomass.

Zooplankton community composition differed in the north vs. south, with a dominance of N‐requiring calanoid copepods with high N:P in the north and P‐requiring cladocerans with low N:P in the south. Also, greater differences in zooplankton community composition were found between subarctic regions (with lower DOC) than between boreal regions (with higher DOC), suggesting that increases in lake DOC and associated declines in lake DIN:TP reduce differences in zooplankton community composition.

The combination of lower lake DIN, higher lake DOC, and lower lake DIN:TP led to reduced zooplankton N:P recycling ratios, possibly by reducing seston N:P and/or by enhancing calanoid copepod dominance in the zooplankton community.

Our findings suggest that the combination of declining N deposition and increasing lake browning in northern high‐latitude lakes will reduce phytoplankton biomass, but will concurrently enhance seston mineral quality and probably also zooplankton biomass and their recycling efficiency of P relative to N.
r2ogs5: Calibration of Numerical Groundwater Flow Models with Bayesian Optimization in R
Authors: Schad Philipp , Boog Johannes , Kalbacher Thomas
Published: June 2022

Large‐scale and high‐resolution groundwater models are currently becoming increasingly important in order to clarify the extent to which climate trends and extreme weather affect the groundwater balance regionally. As a result, the parameterization of groundwater models is becoming more detailed and more complex, making conventional calibration methods too time‐consuming. Moderating the computational demand to find optimal solutions for the resulting potentially multi‐modal objective function requires intelligent and efficient global optimization methods. Moreover, the increasing use of modern scripting languages R and Python to craft environmental analysis workflows calls to integrate groundwater flow simulators in such. Here we introduce and exemplify r2ogs5, a tool that integrates version 5 of the open‐source simulation software OpenGeoSys into the programming language R. r2ogs5 allows for calibration of numerical groundwater flow models with a sequential model‐based optimization approach that combines Bayesian optimization (BO) with surrogate modeling. Here, we describe the structure and function of r2ogs5 as well as the implemented calibration method. We then demonstrate the calibration method by calibrating 4 and 12 parameters of two simple groundwater flow models. The results indicate that this method needs fewer runs of the groundwater flow model than conventional gradient search and Latin hypercube sampling in case of the 12 parameter model. We believe that our method offers the potential to calibrate computationally expensive groundwater flow models. r2ogs5 supports groundwater flow modelers to access the statistical analysis and visualization capabilities of the R language and is a valuable tool for geoscientists already using R.
Coping styles and mental health outcomes of community members affected by black summer 2019–20 bushfires in Australia
Authors: Usher Kim , Durkin Joanne , Douglas Lesley , Coffey Yumiko , Bhullar Navjot
Published: June 2022

The aim of this study was to investigate coping styles, posttraumatic stress, and mental health symptoms among a sample of community members affected by 2019–20 Australian bushfires. Using a convenience sampling approach, an online survey was used to assess a range of coping strategies, posttraumatic stress and symptoms of depression, anxiety, and stress among the affected community members of Black Summer bushfires. The results revealed that study participants reported moderate symptoms of depression and stress, and severe levels of anxiety. Additionally, participants reported use of both approach and avoidance coping strategies following the bushfire event as well as experiencing symptoms of posttraumatic stress, such as having intrusive thoughts and symptoms of avoidance and hyperarousal. Despite the durability of many individuals, others remain affected by the event and there is evidence there may be longer term mental health consequences of the bushfires for some people. Given these findings, it is imperative that mental health services be readily available for people in the bushfire‐affected areas. Mental health nurses have an important role to play in supporting individuals affected by disasters. Awareness of the short‐ and long‐term impacts of disasters on the mental health of people is paramount for mental health nurses.
Research on entropy weight multiple criteria decision‐making evaluation of metro network vulnerability
Authors: Chen Minggao , Mao Jun , Xi Yanhong
Published: June 2022

When the subway network system has insufficient resilience and strong vulnerability, the network operation function will be greatly attenuated or even lost due to the failure of key nodes or lines. Evaluating the vulnerability of the metro network is one of the keys to prevent and control risks. This paper proposes an entropy weight multiple criteria decision‐making evaluation method that combines the vulnerability indexes of agglomeration, network efficiency, and network traffic with the multiple criteria decision‐making method, classifies the vulnerability of subway stations with a clustering idea, and analyzes the most vulnerable area of the Beijing Metro network with the Newman fast algorithm. The results show that this method can evaluate the node vulnerability of metro networks more accurately and effectively by considering the topological vulnerability, functional vulnerability, and human flow function vulnerability of the networks. According to the node vulnerability value, the stations can be divided into five grades: The station at the intersection of the loop and radial lines and its adjacent stations have a higher vulnerability level. The vulnerability level of the downtown core area and suburban line terminal stations is relatively low, and the areas with the greatest vulnerability of the Beijing Metro network are mainly located on the east and west sides of the core city.
Assessment of the frequency of Mycobacterium bovis shedding in the faeces of naturally and experimentally TB infected cattle
Authors: Palmer Si , Williams Gareth A. , Brady Colm , Ryan Eoin , Malczewska Karolina , Bull Tim J. , Hogarth Philip J. , Sawyer Jason
Published: June 2022

Aims

To assess the prevalence of Mycobacterium bovis bacilli in faecal samples of tuberculous cattle, and to better understand the risk of environmental dissemination of bovine tuberculosis (TB) through the spreading of manure or slurry.

Methods and Results

Faecal samples were collected from 72 naturally infected cattle with visible lesions of TB that had reacted to the tuberculin skin test and 12 cattle experimentally infected with M. bovis. These were examined by microbial culture and PCR to assess the presence of M. bovis bacilli. There were no positive cultures from any naturally infected test reactor animal. A single M. bovis colony was cultured from a faecal sample from one of the experimentally infected animals. A single PCR positive result was obtained from the faecal sample of one naturally infected test reactor.

Conclusions

The prevalence of M. bovis in the faecal samples of TB-infected cattle was extremely low.

Significance and Impact of the Study

The results suggest that the risk of spreading TB through the use of slurry or manure as an agricultural fertilizer is lower than that suggested in some historical literature. The results could inform a reconsideration of current risk assessments and guidelines on the disposal of manure and slurry from TB-infected herds.
Plant sterol hyperabsorption caused by uncontrolled diabetes in a patient with a heterozygous ABCG5 variant
Authors: Hasebe Masashi , Iwasaki Yorihiro , Keidai Yamato , Iwasaki Kanako , Honjo Sachiko , Hamasaki Akihiro
Published: June 2022

Plant sterol intake is widely recommended for patients with cardiovascular risk factors based on the inhibitory effect on intestinal cholesterol absorption. Although plant sterols, once absorbed, can promote atherosclerosis, their intake is believed to be safe because of poor absorption, except in rare hyperabsorbers with homozygous ABCG5/8 mutations. We report a case of new‐onset type 1 diabetes accompanied by hypercholesterolemia. At the initial presentation with diabetic ketoacidosis, the patient showed marked hypercholesterolemia. Whole‐exome sequencing revealed a heterozygous pathogenic variant in ABCG5 (p.R419H). The initial serum plant sterol levels were markedly high (sitosterol 32.5 μg/mL, campesterol 66.0 μg/mL), close to the range observed in patients with homozygous ABCG5/8 mutations, which were largely reduced by insulin treatment without ezetimibe. The addition of ezetimibe normalized plant sterol levels. These findings provide the first evidence that uncontrolled diabetes plays a causal role in the pathogenesis of phytosterolemia.
Changes in the height of minute tubercles on the skin of Korean bitterling embryos (Acheilognathus signifer) and embryo movement in the host mussels
Authors: Kim Hyeong Su , Kim Hyun Tae , Park Jun Seong , Im Jae Hyun
Published: June 2022

Bitterlings are freshwater fish that have developed morphological adaptations to improve the survival of their embryos in host mussels. The most well‐known adaptation is the development of minute tubercles, which develop in the early embryonic stage when the embryos have poor swimming ability, and disappear when the embryos reach the free‐swimming stage and leave the host mussels. In this study, the embryonic developmental stages of Acheilognathus signifer were analysed to elucidate the relationship between the changes in the height of the minute tubercles and their movement. The height changes in the minute tubercles in the embryos can be divided into five stages, i.e., formation, growth, peak, reduction and disappearance. The authors found that the embryos lived in the gill demibranch of the host mussel until day 6 after hatching. The movement of embryos to the suprabranchial cavity in the gill demibranch was firstly observed on day 7. At this point, the embryos showed a heartbeat and movement. From day 13, the minute tubercles had almost disappeared, and the hatchlings started swimming outside the host mussels from day 16. These observations highlight the different adaptations of minute tubercles among bitterling groups without wing‐like projections.
Optimization of pulsed mode sonication and in silico molecular docking study for antioxidant properties of mandarin (Citrus reticulata Blanco) peels
Authors: Kumar Ankit , Rout Rahul Kumar , Rao Pavuluri Srinivasa , Prabhakar Pawan
Published: June 2022

The present study is aimed to investigate the extractability of bioactive compounds from mandarin (Citrus reticulata Blanco) peel using a pulsed mode of ultrasonic treatment. Box–Behnken experimental design associated with response surface methodology (RSM) was used for the process optimization. Ultrasound amplitude (60%–80%), time (5–15 min), and duty cycle (.30–.90) were the independent variables investigated to maximize the yield of total phenolic content (TPC), total saponin content (TSC), total flavonoid content (TFC), total condensed tannin (TCT), and antioxidant activity (DPPH and FRAP methods). The optimum predicted values of the TPC (27.23 g GAE/100 g dry weight [DW]), TFC (5.64 g QE/100 g DW), TCT (3.17 mg CE/g DW), TSC (42.36 mg EE/g DW), DPPH (4.01 mg GAE/g DW) and FRAP (13.71 mg TE/g DW) were obtained at conditions: 11.19 min of sonication at a duty cycle of .30 and 77.70% amplitude. Furthermore, in silico investigations of anti‐oxidant properties of major flavonoids were done using molecular docking. The analysis showed a better binding affinity of narirutin for Cytochrome P450 and myeloperoxidase, while hesperidin showed a better binding affinity with lipoxygenase. The results obtained from the study showed better phenolic extraction and high antioxidant activity using pulsed mode sonication. The high binding scores of hesperidin and narirutin for all three key enzymes, as obtained by molecular docking, have shown their therapeutic potential in the development of antioxidant drugs.

Practical Applications

A practical insight of the present research suggests the applicability of optimized pulsed mode extraction conditions for industrial processing of Citrus reticulata Blanco peel, a green technology useful in terms of its biomedical application. The optimized extraction conditions will give a higher yield with reduced time and with less use of extraction solvents. The in silico analysis provides scope for predictive modeling of novel antioxidative drug development using major flavonoid compounds of Citrus reticulata Blanco peel.
The microbiota in eosinophilic esophagitis: A systematic review
Authors: Angerami Almeida Kaylani , de Queiroz Andrade Ediane , Burns Grace , Hoedt Emily C , Mattes Joerg , Keely Simon , Collison Adam
Published: June 2022

Eosinophilic esophagitis (EoE) is an atopic disease of the esophagus that has shown a significant increase in incidence and prevalence in the last 20 years. The etiology of EoE is unclear, and few studies explore the esophageal microbiota in EoE. The local microbiome has been implicated in the pathogenesis of several allergic and inflammatory diseases, such as asthma and eczema. In this study, we performed a systematic review to evaluate differences in the microbiota profile of patients with EoE compared with controls. MEDLINE, Embase, Cochrane Library, Scopus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched to identify studies investigating the microbiota composition in EoE. Three reviewers screened the articles for eligibility and quality. Seven articles underwent full‐text review, and a narrative synthesis was undertaken. The microbiota of the mouth and esophagus are correlated. Patients with active EoE present increased esophageal microbial load and increased abundance in particular species, such as Haemophilus and Aggregatibacter. On the other hand, EoE patients present a decrease in Firmicutes. High microbial load and abundance of Haemophilus are observed in EoE patients, but little evidence exists to demonstrate their influence on inflammation and disease. Understanding microbial signatures in EoE might contribute to the development of novel therapeutic strategies.
Transcriptional regulation of fleshy fruit texture
Authors: Shi Yanna , Li Bai‐Jun , Su Guanqing , Zhang Mengxue , Grierson Donald , Chen Kun‐Song
Published: June 2022

Fleshy fruit texture is a critically important quality characteristic of ripe fruit. Softening is an irreversible process which operates in most fleshy fruits during ripening which, together with changes in color and taste, contributes to improvements in mouthfeel and general attractiveness. Softening results mainly from the expression of genes encoding enzymes responsible for cell wall modifications but starch degradation and high levels of flavonoids can also contribute to texture change. Some fleshy fruit undergo lignification during development and post‐harvest, which negatively affects eating quality. Excessive softening can also lead to physical damage and infection, particularly during transport and storage which causes severe supply chain losses. Many transcription factors (TFs) that regulate fruit texture by controlling the expression of genes involved in cell wall and starch metabolism have been characterized. Some TFs directly regulate cell wall targets, while others act as part of a broader regulatory program governing several aspects of the ripening process. In this review, we focus on advances in our understanding of the transcriptional regulatory mechanisms governing fruit textural change during fruit development, ripening and post‐harvest. Potential targets for breeding and future research directions for the control of texture and quality improvement are discussed.
Therapeutic potential of progesterone in spinal cord injury‐induced neuropathic pain: At the crossroads between neuroinflammation and N‐methyl‐D‐aspartate receptor
Authors: Ferreyra Sol , González Susana
Published: June 2022

In recent decades, an area of active research has supported the notion that progesterone promotes a wide range of remarkable protective actions in experimental models of nervous system trauma or disease, and has also provided a strong basis for considering this steroid as a promising molecule for modulating the complex maladaptive changes that lead to neuropathic pain, especially after spinal cord injury. In this review, we intend to give the readers a brief appraisal of the main mechanisms underlying the increased excitability of the spinal circuit in the pain pathway after trauma, with particular emphasis on those mediated by the activation of resident glial cells, the subsequent release of proinflammatory cytokines and their impact on N‐methyl‐D‐aspartate receptor function. We then summarize the available preclinical data pointing to progesterone as a valuable repurposing molecule for blocking critical cellular and molecular events that occur in the dorsal horn of the injured spinal cord and are related to the development of chronic pain. Since the treatment and management of neuropathic pain after spinal injury remains challenging, the potential therapeutic value of progesterone opens new traslational perspectives to prevent central pain.
Effects of anterior bite planes fabricated from acrylic resin and thermoplastic material on masticatory muscle responses and maximum bite force in children with a deep bite: A 6‐month randomised controlled trial
Authors: Wasinwasukul Passakorn , Nalamliang Napat , Pairatchawan Nalin , Thongudomporn Udom
Published: June 2022

Background

Anterior bite planes are bite‐raising appliances used for deep bite correction. However, muscle responses to anterior bite planes of different harnesses may vary.

Objectives

To prospectively evaluate masticatory muscle activity, muscle balance and maximum bite force (MBF) responses to anterior bite planes fabricated from acrylic resin (ABP) or bi‐laminate thermoplastic (TBP) over 6 months in children with a deep bite.

Methods

Sixty‐six children were randomly assigned to the ABP, TBP or untreated control groups. Masticatory muscle activity, activity index (AC) and percentage overlapping coefficient (POC) were assessed by surface electromyography; MBF, using a custom‐made bite force sensor. Data were collected before, immediately after appliance insertion and after 2 weeks and 1, 3 and 6 months of treatment. Within‐ and between‐group differences were analysed using the one‐way ANOVA/Kruskal‐Wallis and Mann–Whitney U tests (α = .05); Friedman's tests were used to assess within‐group differences over time (α = .08).

Results

At rest, no dependent variables changed throughout the study. At maximum clenching, masticatory muscle activity immediately dropped significantly but returned to baseline values and was equal to the control group at 1–3 months. The ABP group had significantly lower masseter activity and AC than the TBP group after insertion. Neither POC nor MBF were significantly different within or between groups.

Conclusion

Masticatory muscle activity reduced after anterior bite plane insertion but returned to baseline after 1–3 months. Masseter activity decreased significantly more in the ABP group than TBP group. Neither appliance significantly affected POC or MBF.

Clinical trial registration

Thai Clinical Trial Registry (TCTR20210330002).
Identifying metabolic parameters related to severity and extent of periodontitis in down syndrome patients
Authors: Mouchrek Monique Maria Melo , Franco Mayra Moura , da Silva Leslie Alves , Martins Kerry Alynne Campos , Conceição Sueli Ismael Oliveira da , Rodrigues Vandilson Pinheiro , Benatti Bruno Braga
Published: June 2022

Background and Objective

Systemic metabolic status and periodontitis can be related in patients with Down syndrome (DS). The objective of this study was to identify metabolic indicators (anthropometric measurements, blood pressure, and serum markers) related to severity and extent of periodontitis in DS patients.

Methods

A cross‐sectional study was conducted with 49 patients with DS. Periodontal evaluation included the periodontal probing depth (PPD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Periodontitis severity was classified by the stages system. The extent of periodontitis was assessed as the percentage of sites with CAL ≥3 mm, CAL ≥4 mm, PPD ≥4 mm, and PPD ≥5 mm. The metabolic condition of the participants was determined by analyzing anthropometric parameters, blood pressure, and serum markers. Data were analyzed using the Mann–Whitney test, Spearman's correlation coefficient, and multivariate regression analysis.

Results

Periodontitis stage 3/4 was detected in 32.7% of patients, with high values of VPI (54.6 ± 35.8) and GBI (42.4 ± 33.3). The severity of periodontitis was related to higher mean corpuscular hemoglobin (β = .291, p = .028) and mean corpuscular volume values (β = .293, p = .046). Arm circumference measurements were inversely related to CAL ≥3 mm (β = −.408, p = .023), PPD ≥4 mm (β = −.475, p = .006), and PPD ≥5 mm (β = −.443, p = .010).

Conclusions

The findings suggest that the severity and extent of periodontitis may be related to some metabolic parameters in DS patients.
Deciphering the interdependent labyrinth between gut microbiota and the immune system
Authors: Saini A. , Dalal P. , Sharma D.
Published: June 2022

The human gut microbiome interacts with each other and the host, which has significant effects on health and disease development. Intestinal homeostasis and inflammation are maintained by the dynamic interactions between gut microbiota and the innate and adaptive immune systems. Numerous metabolic products produced by the gut microbiota play a role in mediating cross-talk between gut epithelial and immune cells. In the event of an imbalance between the immune system and microbiota, the body becomes susceptible to infections and homeostasis is compromised. This review mainly focuses on the interplay between microbes and the immune system, such as T-cell- and B-cell-mediated adaptive responses to microbiota and signalling pathways for effective communication between the two. We have also highlighted the role of microbes in the activation of the immune response, the development of memory cells and how the immune system determines the diversity of human gut microbiota. The review also explains the relationship of commensal microbiota and their relation to the production of immunoglobulins.
Richness and resilience in the Pacific: DNA metabarcoding enables parallelized evaluation of biogeographic patterns
Authors: Kennedy Susan , Calaor Jerilyn , Zurápiti Yazmín , Hans Julian , Yoshimura Masashi , Choo Juanita , Andersen Jeremy C. , Callaghan Jackson , Roderick George K. , Krehenwinkel Henrik , Rogers Haldre , Gillespie Rosemary G. , Economo Evan P.
Published: June 2022

Islands make up a large proportion of Earth's biodiversity, yet are also some of the most sensitive systems to environmental perturbation. Biogeographic theory predicts that geologic age, area, and isolation typically drive islands' diversity patterns, and thus potentially impact non‐native spread and community homogenization across island systems. One limitation in testing such predictions has been the difficulty of performing comprehensive inventories of island biotas and distinguishing native from introduced taxa. Here, we use DNA metabarcoding and statistical modelling as a high throughput method to survey community‐wide arthropod richness, the proportion of native and non‐native species, and the incursion of non‐natives into primary habitats on three archipelagos in the Pacific – the Ryukyus, the Marianas and Hawaii – which vary in age, isolation and area. Diversity patterns largely match expectations based on island biogeography theory, with the oldest and most geographically connected archipelago, the Ryukyus, showing the highest taxonomic richness and lowest proportion of introduced species. Moreover, we find evidence that forest habitats are more resilient to incursions of non‐natives in the Ryukyus than in the less taxonomically rich archipelagos. Surprisingly, we do not find evidence for biotic homogenization across these three archipelagos: the assemblage of non‐native species on each island is highly distinct. Our study demonstrates the potential of DNA metabarcoding to facilitate rapid estimation of biogeographic patterns, the spread of non‐native species, and the resilience of ecosystems.
Brain parenchymal angiomatoid fibrous histiocytoma and spinal myxoid mesenchymal tumor with FET: CREB fusion, a spectrum of the same tumor type
Authors: Kim Na Rae , Kim Seong‐Ik , Park Jin Woo , Park Chul‐Kee , Chung Chun Kee , Choi Seung‐Hong , Yun Hongseok , Park Sung‐Hye
Published: June 2022

Angiomatoid fibrous histiocytomas (AFH) is a rare soft tissue tumor of intermediate malignant potential, and its histology is diverse. It can occur in several organs including intracranial and soft tissues. Here, we report two cases of brain parenchymal classic AFH and spinal extramedullary myxoid mesenchymal tumor with clinicopathological and molecular investigations by next‐generation sequencing and a comprehensive review. The current brain parenchymal AFH occurred in a 79‐year‐old woman, and the spinal myxoid mesenchymal tumor arose in the thoracic spine of a 28‐year‐old woman; both harbored FET:CREB fusion. The current brain parenchymal AFH has not recurred for 15‐months follow‐up period, but the spinal myxoid mesenchymal tumor recurred three times and metastasized to T8 spine level for 30‐months follow‐up period. We reviewed 40 reported cases of central nervous system (CNS) AFHs/myxoid mesenchymal tumors including our two cases to identify clinicopathological features and biological behaviors. They occur with a slight female predominance (M:F = 1:1.7) in children and young adults (median age: 17 years; range: 4–79 years old). Approximately 80% of CNS AFHs were younger than 30 year. Most of them were dura‐based and were not just intracranial tumors as they occurred anywhere in the CNS including spinal dura. EWSR1 rearrangement was the most common driver (98%), including FET:CREB (33%), EWSR1:ATF1 (30%), and EWSR1:CREM (27%) fusions, but FUS:CREM fusion (2%) was also present. During the follow‐up period (median: 27 months), 43% (17/40) of CNS AFHs recurred between two months and 11 years, and multiple recurrences were also observed. One case showed metastases to the lymph nodes and vertebrae, and among 11 cases that resulted in death, four cases provided available clinical data. Because these tumors are identical to soft tissue AFH or primary pulmonary myxoid sarcoma with an FET:CREB fusion in morphological and immunohistochemical spectra, the authors propose incorporating the two tumor terms into one.
Sex differences in fronto‐limbic white matter tracts in youth with mood disorders
Authors: Hermens Daniel F. , Jamieson Daniel , Fitzpatrick Lauren , Sacks Dashiell D. , Iorfino Frank , Crouse Jacob J. , Guastella Adam J. , Scott Elizabeth M. , Hickie Ian B. , Lagopoulos Jim
Published: June 2022

Aims

Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders.

Methods

Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self‐report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto‐limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors.

Results

Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed.

Conclusions

Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.
Analysis of existing “how to” manuals for the care of inpatients with epidermolysis bullosa
Authors: Breneman Alyssa , Morel Kimberly D. , Paller Amy S. , Levin Laura E.
Published: June 2022

“How to” skin care manuals assist health care professionals caring for hospitalized patients with epidermolysis bullosa and other disorders. Manuals created by Epidermolysis Bullosa Clinical Research Consortium sites were collected and analyzed. Analysis of manuals revealed variable content. Creating a unified, optimized “how” to manual would benefit providers and patients.
Monitoring of Peronospora destructor oospores from field samples using real‐time PCR
Authors: Nishimura Fumihiro , Fujisawa Haruka , Mori Mitsutaka , Nakashima Chiharu , Nakanishi Mitsuru , Iwamoto Yutaka , Mimuro Genki , Nakamura Yoshihide , Komori Mayu , Ikeda Kenichi
Published: June 2022

Onion downy mildew caused by Peronospora destructor has been widespread in Japan since 2016. Soil disinfection and use of fungicides have been implemented as control measures against oospores in the soil, which are the primary source of infection. Measurements of oospore density are needed to clarify the risk of disease development and inform disease management. In this study, an experimental system capable of detecting P. destructor DNA from field samples was developed. A TaqMan probe‐type primer was used to target the coxII (cytochrome c oxidase subunit II) region of the mitochondrial genome of P. destructor and no false positives were observed. Using this method, the detection limit was equivalent to 5 oospores of P. destructor/g soil in grey lowland soil and andosol. The correlation coefficient between oospore density and the primary infection rate was investigated by testing soil samples from 115 fields. Although no correlations between oospore density and the primary infection were observed in pesticide‐treated fields, significant correlations were observed in untreated fields. Continuous cropping of onions increased the oospore density. The correlation between primary and secondary infection was relatively weak, and the negative predictive value of primary infection was relatively high (89.0). These results suggest that the disease‐risk potential of onion downy mildew is very high, and thus it is necessary to set a low pathogen detection threshold. The system presented here provides a highly sensitive method for supporting decision‐making aimed at disease control.
Cupids of Colour: Gods of African Appearance at Sixteenth‐Century German Courts
Authors: Alff Carolin , Grasskamp Anna
Published: June 2022

While very few portraits of men and women of African origin by early modern German artists have survived, people of colour feature in great numbers in sixteenth‐century engravings, costume albums, collectibles and visual representations of court spectacles. Some of these sources represent men of African appearance as Mercury and his son Cupid, the god of desire. This motif's emergence was informed by the German reception of visual records on conquest and exploration by non‐German authors and further shaped by the local frameworks of courtly entertainment. The politics of viewing as defined by sixteenth‐century artists and their commissioners amounted to an appropriation of the other in the artfully created spaces of theatrical performance and collecting, enabling the temporary presentation of men of colour as gods that was in stark contrast with the objectification and commodification of their lives by the early modern slave trade.
Risk analysis under attack: How risk science can address the legal, social, and reputational liabilities faced by risk analysts
Authors: Thekdi Shital A. , Aven Terje
Published: June 2022

The role of the risk analyst is critical in understanding and managing uncertainty. However, there is another type of uncertainty that is rarely discussed: The legal, social, and reputational liabilities of the risk analyst. Recent events have shown that professionals participating in risk analysis can be held personally liable. It is timely and important to ask: How can risk science guide risk analysis with consideration of those liabilities, particularly in response to emerging and unprecedented risk. This paper studies this topic by: (1) Categorizing how professionals with risk analysis responsibilities have historically been held liable, and (2) developing a framework to address uncertainty related to those potential liabilities. The result of this framework will enable individual analysts and organizations to investigate and manage the expectations of risk analysts and others as they apply risk principles and methods. This paper will be of interest to risk researchers, risk professionals, and industry professionals who seek maturity within their risk programs.
Heterogeneous Graphical Model for Non-Negative and Non-Gaussian PM2.5 data
Authors: Zhang Jiaqi , Fan Xinyan , Li Yang , Ma Shuangge
Published: June 2022

Studies on the conditional relationships between PM2.5 concentrations among different regions are of great interest for the joint prevention and control of air pollution. Because of seasonal changes in atmospheric conditions, spatial patterns of PM2.5 may differ throughout the year. Additionally, concentration data are both non-negative and non-Gaussian. These data features pose significant challenges to existing methods. This study proposes a heterogeneous graphical model for non-negative and non-Gaussian data via the score matching loss. The proposed method simultaneously clusters multiple datasets and estimates a graph for variables with complex properties in each cluster. Furthermore, our model involves a network that indicate similarity among datasets, and this network can have additional applications. In simulation studies, the proposed method outperforms competing alternatives in both clustering and edge identification. We also analyse the PM2.5 concentrations' spatial correlations in Taiwan's regions using data obtained in year 2019 from 67 air-quality monitoring stations. The 12 months are clustered into four groups: January–March, April, May–September and October–December, and the corresponding graphs have 153, 57, 86 and 167 edges respectively. The results show obvious seasonality, which is consistent with the meteorological literature. Geographically, the PM2.5 concentrations of north and south Taiwan regions correlate more respectively. These results can provide valuable information for developing joint air-quality control strategies.