bluuebunny/crossref_metadata_2025 huggingface dataset:
A mechanistic insight into sources of error of visual working memory in multiple sclerosis
Authors: Motahharynia Ali , Pourmohammadi Ahmad , Adibi Armin , Shaygannejad Vahid , Ashtari Fereshteh , Adibi Iman , Sanayei Mehdi
Published: July 2023

Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, MGL were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM deficit in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) was responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.
Breaking enhancers to gain insights into developmental defects
Authors: Armendariz Daniel A , Sundarrajan Anjana , Hon Gary C
Published: July 2023

Despite ground-breaking genetic studies that have identified thousands of risk variants for developmental diseases, how these variants lead to molecular and cellular phenotypes remains a gap in knowledge. Many of these variants are non-coding and occur at enhancers, which orchestrate key regulatory programs during development. The prevailing paradigm is that non-coding variants alter the activity of enhancers, impacting gene expression programs, and ultimately contributing to disease risk. A key obstacle to progress is the systematic functional characterization of non-coding variants at scale, especially since enhancer activity is highly specific to cell type and developmental stage. Here, we review the foundational studies of enhancers in developmental disease and current genomic approaches to functionally characterize developmental enhancers and their variants at scale. In the coming decade, we anticipate systematic enhancer perturbation studies to link non-coding variants to molecular mechanisms, changes in cell state, and disease phenotypes.
How hibernation in frogs drives brain and reproductive evolution in opposite directions
Authors: Liao Wen Bo , Jiang Ying , Jin Long , Lüpold Stefan
Published: July 2023

Environmental seasonality can promote the evolution of larger brains through cognitive and behavioral flexibility but also hamper it when temporary food shortage is buffered by stored energy. Multiple hypotheses linking brain evolution to resource acquisition and allocation have been proposed, albeit separately for different groups of birds or mammals rather than being directly compared within any single group. Here, using direct tissue measurements and experimentally validated brumation (‘hibernation’) parameters, we integrated these hypotheses across frogs in the context of varying brumation duration and its environmental correlates. We show that protracted brumation reduces brain size and instead promotes reproductive investments, likely in response to brumation-dependent changes in the socio-ecological context that ultimately affect the operation of sexual selection and evolution of mating systems. Our results reveal novel insight into the complex processes of brain and reproductive evolution in organisms whose ‘cold-blooded’ metabolism is particularly susceptible to environmental seasonality.
Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2
Authors: Bulos Maya L , Grzelak Edyta M , Li-Ma Chloris , Chen Emily , Hull Mitchell , Johnson Kristen A , Bollong Michael J
Published: July 2023

Yes-associated protein (YAP), the downstream effector of the evolutionarily conserved Hippo pathway, promotes cellular proliferation and coordinates certain regenerative responses in mammals. Small molecule activators of YAP may, therefore, display therapeutic utility in treating disease states involving insufficient proliferative repair. From a high-throughput chemical screen of the comprehensive drug repurposing library ReFRAME, here we report the identification of SM04690, a clinical stage inhibitor of CLK2, as a potent activator of YAP-driven transcriptional activity in cells. CLK2 inhibition promotes alternative splicing of the Hippo pathway protein AMOTL2, producing an exon-skipped gene product that can no longer associate with membrane-bound proteins, resulting in decreased phosphorylation and membrane localization of YAP. This study reveals a novel mechanism by which pharmacological perturbation of alternative splicing inactivates the Hippo pathway and promotes YAP-dependent cellular growth.
Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells
Authors: Schenberg Louise , Palou Aïda , Simon François , Bonnard Tess , Barton Charles-Elliot , Fricker Desdemona , Tagliabue Michele , Llorens Jordi , Beraneck Mathieu
Published: July 2023

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.
DMRT1 is a Testis Determining Gene in Rabbits and is Also Essential for Female Fertility
Authors: Dujardin Emilie , André Marjolaine , Dewaele Aurélie , Mandon-Pépin Béatrice , Poulat Francis , Frambourg Anne , Thépot Dominique , Jouneau Luc , Jolivet Geneviève , Pailhoux Eric , Pannetier Maëlle
Published: July 2023

DMRT1 is the testis-determining factor in several species of vertebrates, but its involvement in mammalian testes differentiation, where
SRY
is the sex-determining gene, remains ambiguous. So far, DMRT1 loss of function has been described in two mammalian species and induces different phenotypes: disorders of sex development (XY DSD) in men and male infertility in mice. We thus abolished the DMRT1 expression by CRISPR/Cas9 in a third species of mammal, the rabbit. First, we observed that gonads from XY
DMRT1
-/-
rabbit fetuses differentiated like ovaries, highlighting that DMRT1 is involved in testis determination. In addition to SRY, DMRT1 is required in the supporting cells to increase the expression of the
SOX9
gene, which heads the testicular genetic cascade. Second, we highlighted another function of DMRT1 in the germline since XX and XY
DMRT1
-/-
ovaries did not undergo meiosis and folliculogenesis. XX
DMRT1
-/-
adult females were sterile, showing that DMRT1 is also crucial for female fertility. To conclude, these phenotypes indicate an evolutionary continuum between non-mammalian vertebrates such as birds and non-rodent mammals. Furthermore, our data support the potential involvement of
DMRT1
mutations in different human pathologies, such as XY DSD and male and female infertility.
Water Quality Assessment of Sahastradhara Stream, Dehradun, Uttarakhand, India
Authors: Kaur Simerjit , Naseer Sahreen
Published: July 2023

Sahastradhara stream is a main attraction of tourist as well as source of household and potable water for the region and the surrounding villages. The stream is being polluted attributable to a variety of human-made activities and water quality is being deteriorated. During these studies, water samples were collected from the three different The physical-chemical characteristics of the water, including temperature, pH, transparency, turbidity, DO, BOD, CO2, alkalinity, and chloride, were analysed at Site-I (the reference Site), Site-II (the more popular tourist destination, severely contaminated Site), and Site-III (moderately polluted). The Physico-chemical parameters were recorded highest at Site-II (DO 7.5mg/l), Turbidity (58.1-80.16 NTU), Alkalinity (245.4-308.2mg L-1), pH (6.1-7.2), temperature (25.60C-27.60C), BOD (1.5 mg/l-2.6mg/l), CO2 (1.5-1.83) followed by S-3 (temperature 26.2-27.20C, pH 7.1-7.2, tur. 79.2-81.1cm, DO 8.1-8.2mg/l, CO2 1.62-1.81, Alkalinity 255.6-262.2 mg/l, BOD, 2.3-2.4 mg/l, Chloride 32.1-32.5 mg/l) and S-I (temperature 25.6-26.30C, pH 7.0-7.1, turbidity 60.2-68.2cm, DO 8.5, CO2, 1.53-1.62 mg/l, Alkalinity, 250.2-256.6 mg/l, BOD,1.5-1.6 mg/l, chloride, 30.0-30.2 mg/l). The study has shown that water at Site-I of Sahastradhara stream is suitable for human use and other purposes, whereas Due to a major change in the water quality of the Sahastradhara stream brought on by various touristic and anthropogenic activities, the water at Sites II and III is unfit for all uses. At the 5% level of significance, every parameter changed considerably over the study period.
Selection of Suitable Genotypes Based on Physiological and Morphological Traits in Rapeseed (Brassica napus L.)
Authors: Sadeghizadeh Malihe
Published: July 2023

Aims: Rapeseed (Brassica napus L.) as one of the most important oilseeds in the world, has a special role in cultivation and plant breeding research. Especially, the properties of rapeseed oil compounds, which have high oleic acid, antioxidant and positive effects on cholesterol, blood sugar control, blood pressure and cancer, make it one of the healthiest and most important edible oils in the world and an alternative to use Other vegetable oils have been introduced in recent years. Evaluation of different genotypes of Rapeseed in terms of different traits and selection of the most appropriate genotypes can be effective in realizing the goals of plant breeding.

Study Design:  In order to conduct the experiment, a randomized complete block design (RCBD) was used in three replications.

Place and Duration of Study: This study was conducted in Varamin region of Iran in 2019-2020.

Methodology: Each experimental plot had 4 rows of cultivation at a distance of 50 cm. The seeds were planted at a distance of 10 cm from each other and all steps such as watering and weeding were done regularly and manually.

Results: The results of analysis of variance at the level of 0.01 indicated that the evaluated genotypes have significant differences in terms of all traits except the number of grains in the pod. In the means comparison of the traits, grain yield and oil percentage traits, which were selected as the most important traits, the Licord genotype was selected as the most favorable genotype. Based on the correlation analysis between the traits, the trait of grain yield had a positive and significant correlation with the traits of thousand grain weight, number of pods in the main stem, pod weight, days to flowering and oil percentage. Based on analysis of the main components, the first five components accounted for more than 74% of the variance of the total data. The drawn polygon diagram also identified Licord, Hyola-401, SLM046, Modena and Option 500 genotypes as desirable genotypes.

Conclusion: Non-invasive independent predictors for screening esophageal varices may decrease medical as well as financial burden, hence improving the management of cirrhotic patients. These predictors, however, need further work to validate reliability.
Freshwater Lobster (Cherax quadricarinatus) Cultivation in Cangkuang District, Bandung Regency, West Java, Indonesia: A Case Study
Authors: Andriani Yuli , Pratama Rusky I. , Harlina Putri Widyanti
Published: July 2023

The fisheries sector presents significant economic opportunities for enhancing income and contributing to regional development. Bandung Regency, known for its abundant fishery resources, has emerged as a key player in this sector. Among the various fishery commodities, freshwater crayfish has gained popularity due to its market advantages and ease of cultivation. The development of crayfish cultivation in Bandung Regency offers an excellent opportunity for local farmers and investors, leveraging the region's abundant resources. Initially favoured as a consumable commodity, crayfish has now gained traction as an ornamental fish. Its higher profitability, shorter maintenance time, lower risks, and increased profits have contributed to its attractiveness as an ornamental fish commodity. This paper presents a case study on the development of freshwater crayfish cultivation in Cangkuang District, Bandung Regency, West Java, Indonesia, aiming to enhance the income of ornamental fish cultivators by maximizing cultivation productivity. Furthermore, Bandung Regency stands out as a promising area for aquaculture development, boasting vast public waters and a thriving fishery sector. Ornamental fish cultivation plays a significant role, with local farmers producing various species, including koi, comet goldfish, flowerhorn, and crayfish. To optimize crayfish cultivation, this study provides insights into culture techniques, including site selection, cultivation containers (such as ponds and aquariums), water quality management, feeding practices, parent selection, brood care, spawning processes, larvae rearing, and market analysis. By implementing these techniques, the cultivation of freshwater crayfish can flourish in Bandung Regency, contributing to the economic growth and income generation in the region.
Influence of Biofertilizer and Zinc on Yield and Economics of Barley (Hordeum vulgare L.)
Authors: Sumit  , Singh Rajesh , Indu Thakur , Choudhary Dilip
Published: July 2023

The field experiment "Influence of Biofertilizer and Zinc on Yield and Economics of Barley" was carried out during the Rabi season of 2022 at Crop Research Farm in the Department of Agronomy, Naini Agriculture Institute, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, Uttar Pradesh. The treatment consisted of Biofertilizers [Azotobacter, PSB and Azotobacter + PSB], Zn (20, 25 and 30 kg/ha) and control. The experiment was designed using Randomized Block Design (RBD) and reproduced three times. The soil in the experimental area was sandy loam with a pH of 8.0, 0.62% organic carbon, 225 kg/ha available nitrogen, 38.2 kg/ha available phosphorus, and 240.7 kg/ha available potassium. Azotobacter + PSB + Zn 30 kg/ha increases grain production (4.29 t/ha), straw yield (6.72 t/ha), gross return (108675 INR/ha), net return (78555 INR/ha) and B:C (2.61).
Effect of Biochar Produced from Paddy Husk and Coconut Frond on Soil Physical Properties and Productivity of Ginger in a Laterite Soil
Authors: Jabin P. P. Nihala , Rani B.
Published: July 2023

The effect of biochar produced from paddy husk and coconut frond on soil physical properties and yield of ginger crop was studied in a laterite soil of Kerala, India. The treatments included paddy husk biochar (PHB) and coconut frond biochar (CFB) each @ 10, 20 and 30 t ha-1 + NPK as per KAU package of practices (KAU POP) recommendation, KAU POP alone (30 t FYM + 75: 50: 50 kg NPK ha-1) and absolute control. The recovery of paddy husk biochar (PHB) was 50% and that of coconut frond biochar (CFB) was 40%. Physical properties of the soil were significantly improved by the application of biochar compared to FYM as per KAU POP application. Specific surface area (68.74 and 2.56 m2 g-1 respectively) and water holding capacity (276.33 and 256.51% respectively) were higher for PHB compared to CFB whereas bulk density was lower for PHB (0.27Mg m-3) than CFB (0.35 Mg m-3). Biochar application reduced the bulk density, increased the water holding capacity and water stable aggregates of soil. Plant height, rhizome spread, and ginger yield were calculated towards interpreting the direct influence of biochar on growth of ginger. All these parameters were positively influenced by the incorporation of biochar at different rates. The highest ginger yield was obtained for PHB @ 30 t ha-1 (13964.2 kg ha-1) which was on par with CFB @ 30 t ha-1 (13418.3 kg ha-1). From the investigations, it can be concluded that application of PHB or CFB @ 30 or 20 t ha-1 along with NPK as per KAU POP produced significantly higher yield than FYM treatment as per KAU POP can be considered as the economically viable treatments in laterite soil.
Effect of Phosphorus and Hydrogel on Growth and Yield of Maize (Zea mays L.)
Authors: Jamwal Shubham , Dawson Joy , Kashyap Cheenu
Published: July 2023

A field experiment was conducted during Rabi 2022 at Crop Research Farm, Department of Agronomy, Sam Higginbottom University of Agriculture Technology and Sciences, Prayagraj, (U.P) India. To evaluate the effect of phosphorus and hydrogel on growth and yield of maize (Zea mays L.). Both phosphorus and Hydrogel was broadcasting in the field before sowing and mixed well in the soil. The growth attributes which was plant height (231.54 cm) and dry weight (178.19 g/plant) was significantly increased with increasing the level of phosphorus (25, 50, 75 kg/ha) and hydrogel (2.5, 5, 7.5 kg/ha) and maximum was obtained with application of phosphorus (75 kg/ha) and hydrogel (7.5 kg/ha) with highest effective number of cobs/plant (2.60), cob length (14.63 cm), number of rows/cob (11.91), number of grains/cob (326.39), grain yield (4.95 t/ha), stover yield (6.72 t/ha), harvest index (42.30%).
Influence of Nitrogen Levels and Microbial Inoculants on Yield and Economics of French Bean (Phaseolus vulgaris L.)
Authors: Panda Alok Kumar , Singh Rajesh , Indu Thakur , Choudhary Dilip
Published: July 2023

The field experiment entitled “Influence of Nitrogen levels and Microbial inoculants on Yield and Economics of French bean" was conducted during rabi season, 2022 at Crop Research Farm in the Department of Agronomy, Naini Agriculture Institute, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj Uttar Pradesh. The soil in the experimental area was sandy loam with pH (8.0), Organic Carbon (0.42%), Available N (180.58 kg/ha), Available P (15.54 kg/ha), and Available K (198.67 kg/ha). The treatment consisted of two factors, Factor-1 levels of Nitrogen (75,100,125 kg/ha) and factor-2 Microbial inoculants (Rhizobium, PSB & Rhizobium +PSB). The experiment was layout in Randomized Block Design (RBD) with 10 treatments and replicated thrice. It was noticed that application of Nitrogen levels and Microbial inoculants had a significant effect on growth, yield, and yield parameters. The results indicated that the higher seed yield (22.47 q/ha), stover yield (50.08 q/ha), harvest index (30.95%), gross return (133601.00 INR/ha), net return (91333.00 INR/ha) and benefit-cost ratio (2.16) were observed in treatment 6, which involved the seed inoculation of Rhizobium and PSB along with the soil application of Nitrogen 100 kg/ha. So, in order to get higher productivity and returns from French bean, application of 100kg N/ha along with seed inoculation with phosphate solubilizing bacteria (PSB) and Rhizobium should be followed in sub-humid condition of Prayagraj, UP.
Soil Microbes Expertly Balancing Nutrient Demands and Environmental Preservation and Ensuring the Delicate Stability of Our Ecosystems- A Review
Authors: Srivastava Priya , Sachan Kushal , Baskar P. , Saikanth D. R. K. , Lytand Wankasaki , Kumar R. K. M. Harish , Singh Bal Veer
Published: July 2023

It scrutinizes the critical role of soil microbes in balancing nutrient demands and environmental preservation, thereby ensuring the stability of our ecosystems. The document elucidates how these microscopic organisms play a pivotal role in various ecosystem processes such as nutrient cycling, organic matter decomposition, and the promotion of plant health. It details how their metabolic processes influence soil fertility and plant growth, maintaining a fine equilibrium between the soil's nutrient demand and environmental conservation. The review stresses the influence of microbes on soil health and their potential role in mitigating climate change through carbon sequestration, demonstrating their significance beyond primary production. The correlation between microbial communities, climate change, and soil degradation is emphasized, showing how these factors interact in a complex, interconnected network. Modern microbial management strategies, highlighting sustainable methods to exploit their potential in agriculture and environmental conservation. It advocates for more research into soil microbiome functionality, with a special focus on the impact of human activities and climate change. By emphasizing that soil microbes, although invisible, carry profound implications for global sustainability and food security. By optimizing microbial functions, we can improve soil health and fertility, contributing significantly to ecosystem resilience and stability.
Evaluate the Efficacy of Different Biopesticides with Imidacloprid against Maize Spotted Stem Borer (Chilo partellus swinhoe) on maize under field conditions
Authors: Singh Abhishek , Yadav Usha
Published: July 2023

An experiment of Maize stem borer Chilo partellus using different Bio-pesticides in field condition was carried out during Kharif 2022-2023 at central Research field SHUATS Prayagraj, UP., India. The management of Maize stem borer was done using 8 different treatments and benefit cost ratios of all the treatments were calculated. Total two sprays were applied to protect the crop from Chilo partellus using randomized block design with three replications. The observations of Chilo partellus 24 hours before (Pre- treatment) and 3rd, 7th and 14th day after spraying (post-treatment) were recorded for computing the percent of larval population reduction. The data were subjected to statistical analysis after appropriate transformation for interpretation. The treatment with recommended insecticide cost benefit ratio and yield is in Imidacloprid 200 SL (T7) (1:5.01) (40.49q/ha) followed by Beauveria bassiana (2 CFU×108 ml) (T1) (1:4.53) (38.45q/ha), Bacillus thuringiensis (108 CFU/ml) (T4) (1:4.41) (37.7q/ha), Metarhizium anisopliae (T2) (1:4.20) (36.79q/ha), NPV (T3) (1:4.03) (35.98q/ha), NSKE @ 5% (T5) (1:3.97) (34.6q/ha), Azadirachtin 0.03% (T6) (1:3.85) (33.57q/ha) Lest monetary return and yieldwas obtained with control (T0) (1:3.52) (28.4q/ha).
Analysis of Phenolic Compounds in Nicotiana tabacum Based on Aqueous Two-Phase Extraction Coupled with Liquid Chromatography
Authors: Wang Hua , Zeng Lina , Ding Hui
Published: July 2023

Background: Phenolic compounds in Nicotiana tabacum L. have anti-tumor, antibacterial, anti-inflammatory, and other pharmacological effects. Therefore, either to optimize the utilization of plant resources or to reduce the physiological harm caused by cigarette, it is necessary to separate and analyze the phenolic compounds in Nicotiana tabacum.

Aim: To develop a protocol for extraction and analysis of phenolic compounds in Nicotiana tabacum. The method based on aqueous two-phase extraction (ATP) should provide a solid experimental basis for future large-scale medical industrial extraction.

Results: Five of phenolic compounds in Nicotiana tabacum including catechol, caffeic acid, coumarin, rutin, and quercetin were extracted with the developed ATP method and analyzed by the optimized liquid chromatography method simultaneously. In the concentration range of 10-200 µg/mL, the linear correlation coefficients of calibration curve for five compounds were all greater than 0.999. The developed ATP extraction method employed 70% acetonitrile water solution as the extractant. The ammonium sulphate was selected as the preferred phase separation salt. The extraction efficiencies of five phenolic compounds were all more than 90%. In concrete sample, the concentrations of five compounds were determined based on acetonitrile/salt ATPE system,

Conclusion: Analysis of phenolic compounds in Nicotiana tabacum was achieved based on acetonitrile/ammonium sulphate ATP extraction coupled with liquid chromatography. The developed ATP extraction protocol employed 70% acetonitrile water solution as the extractant. The ammonium sulphate was selected as the preferred phase separation salt. The accuracy and precision were satisfied. The protocol developed in this study is expected to be applied in medical industry.
NCSTN In-Frame Deletion in Maltese Patients With Hidradenitis Suppurativa
Authors: Mintoff Dillon , Pace Nikolai Paul , Borg Isabella
Published: July 2023

Importance

Hidradenitis suppurativa (HS) is a complex trait that has a monogenic etiology in a subset of patients. Variation in genes that encode proteins of the γ secretase complex, particularly NCSTN, account for few patients who exhibit familial forms of HS. Thus far, extensive genotype-phenotype correlations have been lacking.

Objective

To establish the prevalence of the NCSTN:c.671_682del variant and explore potential genotype-phenotype associations in an ethnically Maltese HS cohort.

Design, Setting, and Participants

This cross-sectional study conducted from December 2021 to September 2022 included patients 18 years or older with a diagnosis of HS as defined by recurrent nodules, abscesses, and/or draining tunnels in typical (axilla, breast, groin, buttock, thighs, and inframammary folds) and less typical (scalp, ear pinnae, neck, arms, antecubital fossae) sites who were recruited from the sole national dermatology reference center servicing the Maltese archipelago. Clinical examination and targeted genetic analysis for an NCSTN deletion that was originally identified through whole-exome sequencing in a family with multigenerational disease were performed.

Exposure

Recruited patients were phenotyped and genotyped for the NCSTN:c.671_682del variant.

Main Outcome and Measures

To determine the prevalence of the NCSTN:c.671_682del variant and establish possible genotype-phenotype associations in the ethnically Maltese HS cohort.

Results

A total of 113 patients with HS (56 women [49.6%]) met the inclusion criteria and were enrolled in this study. The median age of disease onset was 18 years (range, 7-62 years), and the median International Hidradenitis Suppurativa Severity Score System score was 4.39 (range, 1.0-64.0). The NCSTN variant was identified in the heterozygous state in 14 patients (12.4%) from 5 unrelated, nonconsanguineous families of Maltese ethnicity. The variant was not identified in an ethnically matched reference genomic data set of disease-free individuals. Variant carriers manifested HS symptoms earlier and were more likely to exhibit a distinctive HS phenotype, which was characterized by involvement of the scalp, neck, torso, and antecubital fossae. Despite manifesting similar clinical disease severity, variant carriers were more likely to require treatment with adalimumab.

Conclusions and Relevance

The results of this cross-sectional study suggest that monogenic variation in NCSTN is associated with HS in a subset of patients who have a distinct, atypical phenotype.
Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People
Authors: Cloud Geoffrey C. , Williamson Jeff D. , Thao Le Thi Phuong , Tran Cammie , Eaton Charles B. , Wolfe Rory , Nelson Mark R. , Reid Christopher M. , Newman Anne B. , Lockery Jessica , Fitzgerald Sharyn M. , Murray Anne M. , Shah Raj C. , Woods Robyn L. , Donnan Geoffrey A. , McNeil John J.
Published: July 2023

Importance

Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.

Objective

To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.

Design, Setting, and Participants

This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.

Interventions

Daily 100-mg enteric-coated aspirin or matching placebo.

Main Outcomes and Measures

Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.

Results

Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).

Conclusions and Relevance

This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.

Trial Registration

ISRCTN.org Identifier: ISRCTN83772183
Epigenetic silencing of HTATIP2 in glioblastoma contributes to treatment resistance by enhancing nuclear translocation of the DNA repair protein MPG
Authors: Nguyen Thi Tham , Rajakannu Premnath , Pham Minh Diêu Thanh , Weman Leo , Jucht Alexander , Buri Michelle C. , Van Dommelen Kristof , Hegi Monika E.
Published: July 2023

Glioblastoma, the most malignant brain tumor in adults, exhibits characteristic patterns of epigenetic alterations that await elucidation. The DNA methylome of glioblastoma revealed recurrent epigenetic silencing of HTATIP2, which encodes a negative regulator of importin β‐mediated cytoplasmic–nuclear protein translocation. Its deregulation may thus alter the functionality of cancer‐relevant nuclear proteins, such as the base excision repair (BER) enzyme N‐methylpurine DNA glycosylase (MPG), which has been associated with treatment resistance in GBM. We found that induction of HTATIP2 expression in GBM cells leads to a significant shift of predominantly nuclear to cytoplasmic MPG, whereas depletion of endogenous HTATIP2 results in enhanced nuclear MPG localization. Reduced nuclear MPG localization, prompted by HTATIP2 expression or by depletion of MPG, yielded less phosphorylated‐H2AX‐positive cells upon treatment with an alkylating agent. This suggested reduced MPG‐mediated formation of apurinic/apyrimidinic sites, leaving behind unrepaired DNA lesions, reflecting a reduced capacity of BER in response to the alkylating agent. Epigenetic silencing of HTATIP2 may thus increase nuclear localization of MPG, thereby enhancing the capacity of the glioblastoma cells to repair treatment‐related lesions and contributing to treatment resistance.
Identifying the personalized driver gene sets maximally contributing to abnormality of transcriptome phenotype in glioblastoma multiforme individuals
Authors: Xu Jinyuan , Pang Bo , Lan Yujia , Dou Renjie , Wang Shuai , Kang Shaobo , Zhang Wanmei , Liu Yuanyuan , Zhang Yijing , Ping Yanyan
Published: July 2023

High heterogeneity in genome and phenotype of cancer populations made it difficult to apply population‐based common driver genes to the diagnosis and treatment of cancer individuals. Characterizing and identifying the personalized driver mechanism for glioblastoma multiforme (GBM) individuals were pivotal for the realization of precision medicine. We proposed an integrative method to identify the personalized driver gene sets by integrating the profiles of gene expression and genetic alterations in cancer individuals. This method coupled genetic algorithm and random walk to identify the optimal gene sets that could explain abnormality of transcriptome phenotype to the maximum extent. The personalized driver gene sets were identified for 99 GBM individuals using our method. We found that genomic alterations in between one and seven driver genes could maximally and cumulatively explain the dysfunction of cancer hallmarks across GBM individuals. The driver gene sets were distinct even in GBM individuals with significantly similar transcriptomic phenotypes. Our method identified MCM4 with rare genetic alterations as previously unknown oncogenic genes, the high expression of which were significantly associated with poor GBM prognosis. The functional experiments confirmed that knockdown of MCM4 could significantly inhibit proliferation, invasion, migration, and clone formation of the GBM cell lines U251 and U118MG, and overexpression of MCM4 significantly promoted the proliferation, invasion, migration, and clone formation of the GBM cell line U87MG. Our method could dissect the personalized driver genetic alteration sets that are pivotal for developing targeted therapy strategies and precision medicine. Our method could be extended to identify key drivers from other levels and could be applied to more cancer types.
Transmission probability filter optimization for Agility MLC in Monaco treatment planning system
Authors: Thewes Lena , Eckl Miriam , Schneider Frank
Published: July 2023

In the Monte Carlo‐based treatment planning system (TPS) Monaco, transmission probability filters (TPF) are utilized to describe the transmission through the multi leaf collimator (MLC). By having knowledge of the TPF parameters for various photon beam energies, adjusting the MLC transmission parameters becomes easier, enhancing the accuracy of the Monte Carlo algorithm in achieving a dose distribution that closely aligns with the irradiated dose at the Versa HD linear accelerator (linac). The objective of this study was to determine the TPF parameters for 6MV, 10MV, 6MV flattening filter free (FFF) and 10MV FFF for a Versa HD linac equipped with Agility MLC. The TPF parameters were adjusted using point dose measurements and vendor‐provided fields specifically designed to fine‐tune the MLC. After adjusting the TPF parameters, a gamma passing rate (GPR) analysis was conducted on 25 treatment plans to ensure that the Monte Carlo model, with the updated TPF parameters, accurately matched the actual linac delivery. The TPF values ranged from 0.0018 to 0.0032 for leaf transmission and 1.15 to 1.25 for Leaf Tip leakage across the different energies. The average GPR ranged from 97.8% for 10MV FFF to 98.5% for 6MV photon energies. Additionally, the TPF parameters for 6MV obtained in this study were consistent with previously published TPF values for 6MV photon energy. Hence, it was concluded that optimizing the TPF does not need to be performed for every individual Versa HD linac with Agility MLC. Instead, the published parameters can be applied to other Versa HD linacs to enhance clinical accuracy. In conclusion, this study determined the TPF parameters for 6MV and previously unpublished photon energies 10MV, 6MV FFF and 10MV FFF. These parameters can be easily transferred to other facilities, resulting in improved agreement between the dose distribution from the TPS and the linac.
Lowering Expectations: Glucocorticoid Tapering Among Veterans With Rheumatoid Arthritis Achieving Low Disease Activity on Stable Biologic Therapy
Authors: Wallace Beth I. , England Bryant R. , Baker Joshua F. , Rojas Jorge , Sauer Brian C. , Roul Punyasha , Kunkel Gary A. , Braaten Tawnie J. , Petro Alison , Mikuls Ted R. , Cannon Grant W.
Published: July 2023

Objective

In the Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial, 65% of patients with rheumatoid arthritis (RA) in low disease activity (LDA) on stable biologic therapy successfully tapered glucocorticoids. We aimed to evaluate real‐world rates of glucocorticoid tapering among similar patients in the Veterans Affairs Rheumatoid Arthritis registry.

Methods

Within a multicenter, prospective RA cohort, we used registry data and linked pharmacy claims from 2003 to 2021 to identify chronic prednisone users achieving LDA after initiating a new biologic or targeted synthetic disease‐modifying antirheumatic drug (b/tsDMARD). We defined the index date as first LDA occurring 60 to 180 days after b/tsDMARD initiation. The primary outcome of successful tapering, assessed at day 180 after LDA, required a 30‐day averaged prednisone dose both less than or equal to 5mg/day and at least 50% lower than at the index date. The secondary outcome was discontinuation, defined as a prednisone dose of 0 mg/day at days 180 through 210. We used univariate statistics to compare patient characteristics by fulfillment of the primary outcome.

Results

We evaluated 100 b/tsDMARD courses among 95 patients. Fifty‐four courses resulted in successful tapering; 33 resulted in discontinuation. Positive rheumatoid factor, higher erythrocyte sedimentation rate, more background DMARDs, shorter time from b/tsDMARD initiation to LDA, and higher glucocorticoid dose 30 days before LDA were associated with greater likelihood of successful tapering.

Conclusion

In a real‐world RA cohort of chronic glucocorticoid users in LDA, half successfully tapered and a third discontinued prednisone within 6 months of initiating a new b/tsDMARD. Claims‐based algorithms of glucocorticoid tapering and discontinuation may be useful to evaluate predictors of tapering in administrative data sets.
SAMHSA awards $18.9 million for services to youth and families
Authors: Knopf Alison
Published: July 2023

This month the Substance Abuse and Mental Health Services Administration (SAMHSA) announced the award of $18.9 million to 35 community organizations for the Enhancement and Expansion of Treatment and Recovery Services for Adolescents, Transitional Aged Youth, and their Families, otherwise known as the “Youth and Family TREE” program. According to SAMHSA, this program enhances “comprehensive treatment, early intervention and recovery support services for adolescents, ages 12 to 18, and transitional aged youth, ages 16 to 25, with substance use disorders and/or co‐occurring substance use and mental disorders, and their families and primary caregivers.”
Temperature‐Independent Conductive Ceramic for High‐Temperature Strain‐Sensing Applications
Authors: Wu Chao , He Yingping , Li Lanlan , Chen Guochun , Fu Yanzhang , Zeng Yingjun , Xu Lida , Lin Fan , Pan Xiaochuan , Chen Qinnan , Zhao Yang , Sun Daoheng , Hai Zhenyin
Published: July 2023

Temperature‐independent properties are critical for high‐temperature thin‐film strain gauges (TFSGs). In this study, by controlling the electron scattering and tunneling effects in the TiB2/SiCN composites, the environmental interference of temperature fluctuations is successfully eliminated, and a temperature‐independent TFSG is fabricated. The effects of pyrolysis temperature and TiB2 content on the microstructural evolution and electrical properties of the ceramic films are studied. The temperature insensitivity is mainly attributed to the balance between the intrasheet resistance with a positive temperature coefficient of resistance (TCR) and the intersheet resistance with a negative TCR. This composite shows nearly constant resistance values over an ultrawide temperature range of 300–700 °C, with less than 0.05% deviation of the normalized resistance and TCR values as low as 1.6 ppm °C−1. In addition, the TiB2/SiCN films exhibited stable piezoresistive responses, with a gauge factor of 4.28, and the temperature‐independent strain response in the high‐temperature range is verified.
Hybrid Data‐Driven Discovery of High‐Performance Silver Selenide‐Based Thermoelectric Composites
Authors: Shang Wenjie , Zeng Minxiang , Tanvir A. N. M. , Wang Ke , Saeidi‐Javash Mortaza , Dowling Alexander , Luo Tengfei , Zhang Yanliang
Published: July 2023

Optimizing material compositions often enhances thermoelectric performances. However, the large selection of possible base elements and dopants results in a vast composition design space that is too large to systematically search using solely domain knowledge. To address this challenge, a hybrid data‐driven strategy that integrates Bayesian optimization (BO) and Gaussian process regression (GPR) is proposed to optimize the composition of five elements (Ag, Se, S, Cu, and Te) in AgSe‐based thermoelectric materials. Data is collected from the literature to provide prior knowledge for the initial GPR model, which is updated by actively collected experimental data during the iteration between BO and experiments. Within seven iterations, the optimized AgSe‐based materials prepared using a simple high‐throughput ink mixing and blade coating method deliver a high power factor of 2100 µW m−1K−2, which is a 75% improvement from the baseline composite (nominal composition of Ag2Se1). The success of this study provides opportunities to generalize the demonstrated active machine learning technique to accelerate the development and optimization of a wide range of material systems with reduced experimental trials.
Polymer Mechanochemistry in Microbubbles
Authors: Xuan Mingjun , Fan Jilin , Khiêm Vu Ngoc , Zou Miancheng , Brenske Kai‐Oliver , Mourran Ahmed , Vinokur Rostislav , Zheng Lifei , Itskov Mikhail , Göstl Robert , Herrmann Andreas
Published: July 2023

Polymer mechanochemistry is a promising technology to convert mechanical energy into chemical functionality by breaking covalent and supramolecular bonds site‐selectively. Yet, the mechanochemical reaction rates of covalent bonds in typically used ultrasonication setups lead to reasonable conversions only after comparably long sonication times. This can be accelerated by either increasing the reactivity of the mechanoresponsive moiety or by modifying the encompassing polymer topology. Here, a microbubble system with a tailored polymer shell consisting of an N2 gas core and a mechanoresponsive disulfide‐containing polymer network is presented. It is found that the mechanochemical activation of the disulfides is greatly accelerated using these microbubbles compared to commensurate solid core particles or capsules filled with liquid. Aided by computational simulations, it is found that low shell thickness, low shell stiffness and crosslink density, and a size‐dependent eigenfrequency close to the used ultrasound frequency maximize the mechanochemical yield over the course of the sonication process.
Lactic Acid Production from Lignocellulosic Residues: A Case Study Toward Process Integration
Authors: Doménech Pablo , Álvarez Cristina , Moreno Antonio D. , Manzanares Paloma , Ballesteros Ignacio
Published: July 2023

In this study, the production of lactic acid from municipal forestry and greening wastes processed by steam explosion (SE) and enzymatic hydrolysis is reported. The liquid fraction hydrolysate (LFH) obtained after filtration of the steam‐exploded slurry (previously subjected to detoxification) and the enzymatic hydrolysate resulting from the water insoluble solid fraction (WIS‐derived hydrolysate, WDH) are studied as substrate for lactic acid fermentation using an integrated strategy. The fermentation process of WDH using Bacillus coagulans and Lactobacillus rhamnosus shows similar sugar conversion yields of about 0.9 g g−1 (based on consumed glucose). In contrast, the use of detoxified LFH (d‐LFH) completely inhibits B. coagulans, making necessary a previous dilution with the WDH to trigger fermentation when using this microorganism. The best integrated strategy using both d‐LFH and WDH streams and B. coagulans as fermentative strain has a 1:3 d‐LFH:WDH ratio, yielding 0.93 g lactic acid g−1 of consumed sugars and a lactic acid concentration of about 50 g L−1.
YOLOv7‐EAS: A Small Target Detection of Camera Module Surface Based on Improved YOLOv7
Authors: Zou Huatao , He Gang , Yao Yuan , Zhu Feng , Zhou Yang , Chen Xuan
Published: July 2023

The camera module surface may introduce defects in the focusing process, and manual detection of these defects is inefficient and costly. To address this problem, a method to automatically expand the dataset for deep learning models with fewer original images is developed. A defect detection method is also presented, YOLOv7‐EAS, that enhances YOLOv7 for camera module images with complex backgrounds and small target defects. This method introduces NewEIOU Loss, a bounding box regression loss function that extends EIOU Loss with a nonlinear compensation term. This function improves the model's convergence rate to quadratic order. Moreover, the detection head based on ASFF is redesigned to adapt the layer features and spatially filter out irrelevant information to improve the detection rate of small targets. Finally, a 3D attention mechanism is applied to increase the model's ability to extract fine‐grained features without increasing the network parameters. Experimental results show that the improved YOLOv7 algorithm achieves 90.5% mAP for the camera module image dataset, which is 10.7% higher than the original algorithm, at 136 FPS. This method can perform the camera module surface defect detection task more accurately and meet the real‐time requirements of the production line.