bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of kinematic transformation from the Altyn Tagh fault to the Qilian Shan in the northern Tibetan Plateau: from early Cenozoic initiation to mid-Miocene extrusion
Authors: Yang Yizhou , Wang Zhendong , Liu Runchao , Peng Luying , Zhang Changhao , Guo Zhaojie
Published: August 2023

The Altyn Tagh fault has been a crucial tectonic boundary of the Tibetan Plateau during the Cenozoic India-Eurasia collision. However, issues have not been addressed regarding the Cenozoic evolution of the kinematic transformation from the eastern Altyn Tagh fault to the Qilian Shan. Here we focus on the kinematics at a crucial point, the Subei triple junction, along the Altyn Tagh fault, which was recorded by faulting in the Suganhu basin to the south of the junction. We reconstructed the structural pattern of faults and thickness distribution of the Cenozoic strata in the Suganhu basin by integrating seismic profiles, well logging, and topographic data. We inferred that only crustal shortening and thickening in the Danghenan Shan, a prominent topographic high, absorbed the strike-slip displacement along the Altyn Tagh fault during the early Cenozoic. Since the mid-Miocene, strike-slip fault belts within the Suganhu basin were initiated, based on the fault geometry and uneven thickness distribution across the fault belts. We thus proposed a mid-Miocene kinematic transformation realized by blocks extruding southeastward, as well as the crustal shortening and thickening in the entire Qilian Shan. Those blocks are bounded by preexisting weaknesses with lateral movements, and lithospheric heterogeneity played an essential role in the block-scale extrusion.
Progress and indication for use of continuous glucose monitoring in patients with diabetes in pregnancy: a review
Authors: Song Yu , Zhai Xiaodan , Bai Yu , Liu Cong , Zhang Le
Published: August 2023

Gestational diabetes mellitus is one of the most common endocrine diseases that occur during pregnancy. Disorders of blood glucose metabolism during pregnancy can increase the risk of adverse pregnancy outcomes, such as pregnancy-related hypertension, preeclampsia, eclampsia, miscarriage, macrosomia, and neonatal hypoglycemia. Continuous glucose monitoring (CGM) can safely and effectively monitor blood glucose changes in patients with gestational hyperglycemia, thereby reducing adverse pregnancy outcomes. Hence, this article aimed to provide a comprehensive review of the progress and indications for using CGM in pregnant patients with diabetes. CGM can reduce blood glucose fluctuations and the occurrence of serious hypoglycemia and hyperglycemia events and can provide time in range (TIR). TIR is an important indicator of blood glucose level. Patients with a higher TIR during pregnancy have better gestational outcomes.
Preoperative preparation for Graves’ disease
Authors: Xu Tianfeng , Zheng Xun , Wei Tao
Published: August 2023

Thyroidectomy is always regarded as the crucial treatment for Graves’ disease, especially in cases of poor efficacy or excessive side effects of antithyroid- drugs and 131I radioiodine therapy. To decrease the incidence of hemorrhage, thyroid storms and other severe complications during the perioperative period, surgeons explore different therapies to prepare for thyroidectomy. We performed a review of preoperative preparation with a focus on the Graves’ disease population. Most of the previous schemes are effective, which contributes to the smooth operation of patients, but there is no unified standard for preoperative preparation. This review aims to summarize the preoperative preparation of Graves’ disease and the latest developments. Prospective studies with longer follow up-up periods are required to select appropriate preoperative regimens based on personal thyroid statements and to identify target populations of benefit.
Algorithm for planning shelters in oil and gas energy resource-based cities based on artificial intelligence resilient city model
Authors: Liang Jing , Ge Ming
Published: August 2023

Cities based on oil and gas energy resources are crucial to energy production and economic development, but they also face various disasters and security risks. To ensure the safety and well-being of urban residents during disaster events, the planning of urban shelters is crucial. In this paper, comprehensively considering multiple factors such as disaster risk, population distribution, and convenient transportation, the artificial bee colony algorithm is used to optimize the site selection and capacity planning of shelters. By comprehensively evaluating the disaster resistance capacity of urban refuges, the response speed of residents and other related indicators, the planning algorithm of refuges is continuously optimized to better meet the needs of oil and gas energy resource-based cities. The results of the study showed that the average overall disaster resilience of AI-based urban shelters reached 0.64. When the distance to the shelter was 4 km, the average response speed of residents reached 10.22 min, and other indicators also improved. The research shows that the oil and gas energy urban refuge planning algorithm based on the artificial intelligence elastic city model provides an innovative approach for urban planners and disaster managers. Further research and practice will help promote the application of this algorithm in real cities, improving the resilience and disaster resistance of cities and the safety and security level of residents.
Acid leaching of hydrothermally carbonized sewage sludge: phosphorus recovery and hydrochar characteristics
Authors: Shettigondahalli Ekanthalu Vicky , Ender Tommy , Narra Satyanarayana , Antwi Edward , Bej Saptarshi , Nelles Michael
Published: August 2023

The options for managing sewage sludge and its utilization as fertilizer are becoming progressively limited as a result of stringent environmental regulations imposed by the European Union over the past 10 years. The limitation of moisture present in sewage sludge that affects conventional treatment options like incineration can be obviated by using the hydrothermal carbonization (HTC) process. This research investigates the acid leaching of hydrochar produced by hydrothermally carbonizing sewage sludge. The objective is to investigate and compare the effects of formic acid (HCOOH), sulfuric acid (H2SO4), and acetic acid (CH3COOH) at varying pH levels on total phosphorus (TP) mobilization and hydrochar properties. The impact of independent parameters such as carbonization temperature of hydrochar, acid type, acid concentration, and acid leaching retention time on the TP mobilization, chemical oxygen demand (COD) of the leachate, and the fuel characteristic of the hydrochar was explored. A quadratic and cubic model was proposed to correlate the effects of independent parameters on TP and ortho-P mobilization, acid need, COD of leachate, and fuel characteristics of hydrochar using Design of Experiments and Response Surface Modeling. This approach was chosen in order to maximize the amount of data from a constrained number of experimental trials. The outcome of the study indicated a fractional amount of H2SO4 was enough to reach and maintain the lower pH in hydrochar slurry compared to HCOOH and CH3COOH. TP mobilization from solid to liquid is highly favorable in the presence of H2SO4 at lower pH compared to HCOOH and CH3COOH under similar reaction conditions. In addition, it was discovered that lowering the pH using HCOOH and H2SO4 to acid-leach the hydrochar boosted the caloric value of the hydrochar. However, CH3COOH has a contradictory effect.
Changes and driving forces analysis of alpine wetlands in the first meander of the Yellow River based on long-term time series remote sensing data
Authors: Jiang Rui , Liu Jingfeng , Liu Weigang , Zhang Dongqi , Hu Wenhan
Published: August 2023

Introduction

As a vital component of the ecosystem of the Qinghai-Tibet Plateau, alpine wetlands coexist with their vulnerability, sensitivity, and abundant biodiversity, propelling the material cycle and energy flux of the entire plateau ecosystem. In recent decades, climate change and human activities have significantly altered the regional landscape. Monitoring and assessing changes in the alpine wetlands on the Qinghai-Tibet Plateau requires the efficient and accurate collection of long-term information.

Methods

Here, we interpreted the remote sensing data of the first meander of the Yellow River of alpine wetlands from 1990 to 2020 based on Google Earth Engine (GEE) platform, using geographic information system (GIS) and landscape pattern index to analyze the spatial and temporal evolution of wetland landscape patterns, and the primary drivers of changes in wetland area were explored by GeoDetector.

Results

Our result showed that most wetland areas were found in regions with gradients less than 12° and elevations between 3315 and 3600 m. From 1990 to 2010, the area of alpine wetland in the study area decreased by 25.43%. During the period between 2010 and 2020 to the 1990s, the wetland area decreased by 322.9 km2. Conversion to and from grassland was the primary form of wetland transfer out and in, respectively. The overall migration of the wetland centroid in the study area was to the southwest between 1990 and 2010 and to the north between 2010 and 2020. The geometry of the wetland landscape was relatively simple, the landscape was relatively intact, and patches retained a high level of agglomeration and connectivity. However, their level of agglomeration and connectivity was disrupted. A quantitative analysis of the factor detector in GeoDetector revealed that the DEM, slope, and evaporation were the most important driving factors influencing the change of wetland area, with socioeconomic development also influencing changes in the wetland area to a lesser extent.

Discussion

Using interaction detectors, it was discovered that the interaction of various driving factors could better explain the long-term variations in wetland areas, with a greater degree of explanation than that of each driving factor alone.
Evaluation and driving factors analysis of agricultural green development level in Beijing from 1978 to 2022
Authors: Liang Lina , Huai Heju , Tang Xiumei
Published: August 2023

Agricultural green development (AGD) plays an important role in achieving a sustainable society. This paper evaluates the AGD level of Beijing from 1978 to 2022 by means of a comprehensive evaluation method, coupling coordination degree (CCD), and grey relational degree model (GRA) with the purpose of exploring relevant stages and characteristics, as well as analyzing the characteristics of different stages and the coupling relationship of various factors and quantitatively calculating the driving factors for AGD change. The results showed that: 1) the AGD level of Beijing generally improved from 1978 to 2022, mainly involving four stages of steady rising, fluctuating, oscillating decreasing, and rapid upgrading; 2) the CCD of the development subsystems of AGD, agricultural resource utilization, agricultural environment conditions, agricultural industry development, and farmers’ living standard, all rose and the coordination type of each subsystem gradually went through a verge imbalance stage, reluctantly coordinated stage, and primary coordinated stage to an intermediate coordinated stage, and then reached a well-coordinated stage in 2019; 3) the AGD level of Beijing is influenced by economic development, the industrial structure, urbanization, technological progress, and agricultural structure. Finally, some policy suggestions to promote AGD in Beijing are put forward. This paper is of great significance to promoting the green and sustainable development of agriculture in Beijing and provides technical support and policy guidance for AGD in other regions.
A monitoring network for the detection of invasive ambrosia and bark beetles in the Czech Republic: principles and proposed design
Authors: Fiala Tomáš , Holuša Jaroslav
Published: August 2023

Invasive bark beetles pose a threat to native biodiversity and to functional ecosystems and the economic productivity of forests, parks, and orchards. In the Czech Republic, there are six species of invasive ambrosia and bark beetles with a stable natural population, and it can be assumed that other invasive species that will be found. In the Czech Republic, there are no guidelines or methods for the early detection of invasive ambrosia and bark beetles. We propose monitoring at a total of 24 locations considering the following: (i) monitoring approaches used in other countries; (ii) identified entrance gates of invasive ambrosia and bark beetles found in the Czech Republic; (iii) presumed invasive species that occur in surrounding countries and are expanding their range; (iv) substances attractive to all the above mentioned species; (v) commonly available traps; and (vi) minimization of operating costs. Most of the chosen locations are located on the state borders and in river valleys, which are probably the entrance gates to the Czech Republic for invasive ambrosia and bark beetles. In addition, two large timber warehouses where international trade takes place, all international airports and three botanical gardens with tropical greenhouses were selected. Three Theysohn or Ecotrap impact traps should be installed every year at all locations. Traps should be baited with ethanol and exposed from mid-April to the end of July and should be checked every 2 weeks.
Potentials of genotypes, morpho-physio-biochemical traits, and growing media on shelf life and future prospects of gene editing in tomatoes
Authors: Yadav Renu , Jaiswal Sarika , Singhal Tripti , Mahto Rohit Kumar , Verma S. B. , Yadav Ramesh Kumar , Kumar Rajendra
Published: August 2023

Background: To study the genetic basis of the impact of genotypes and morpho-physio-biochemical traits under different organic and inorganic fertilizer doses on the shelf life attribute of tomatoes, field experiments were conducted in randomized block designs during the rabi seasons of 2018–2019 and 2019–2020. The experiment comprised three diverse nutrient environments [T1—organic; T2—inorganic; T3—control (without any fertilizers)] and five tomato genotypes with variable growth habits, specifically Angoorlata (Indeterminate), Avinash-3 (semi-determinate), Swaraksha (semi-determinate), Pusa Sheetal (semi-determinate), and Pusa Rohini (determinate).

Results: The different tomato genotypes behaved apparently differently from each other in terms of shelf life. All the genotypes had maximum shelf life when grown in organic environments. However, the Pusa Sheetal had a maximum shelf life of 8.35 days when grown in an organic environment and showed an increase of 12% over the control. The genotype Pusa Sheetal, organic environment and biochemical trait Anthocyanin provides a promise as potential contributor to improve the keeping quality of tomatoes.

Conclusion: The genotype Pusa Sheetal a novel source for shelf life, organic environment, and anthocyanin have shown promises for extended shelf life in tomatoes. Thus, the identified trait and genotype can be utilized in tomato improvement programs. Furthermore, this identified trait can also be targeted for its quantitative enhancement in order to increase tomato shelf life through a genome editing approach. A generalized genome editing mechanism is consequently suggested.
Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy
Authors: Carbone Maria Luigia , Capone Alessia , Guercio Marika , Reddel Sofia , Silvestris Domenico Alessandro , Lulli Daniela , Ramondino Carmela , Peluso Daniele , Quintarelli Concetta , Volpe Elisabetta , Failla Cristina Maria
Published: August 2023

Introduction

Immunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response.

Methods

To better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.

Results and discussion

Stratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.
The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers
Authors: Biatta Chiara M. , Paudice Michele , Greppi Marco , Parrella Veronica , Parodi Alessia , De Luca Giuseppa , Cerruti Gianna Maria , Mammoliti Serafina , Caroti Cinzia , Menichini Paola , Fronza Gilberto , Pesce Silvia , Marcenaro Emanuela , Vellone Valerio G.
Published: August 2023

Background

we evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.

Methods

patients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).

Results

34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].

Conclusion

immunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.
Simultaneous high-precision, high-frequency measurements of methane and nitrous oxide in surface seawater by cavity ring-down spectroscopy
Authors: Brown Ian J. , Kitidis Vassilis , Rees Andrew P.
Published: August 2023

An automated system was developed using commercially available Cavity Ring-Down Spectroscopy (CRDS) technology (Picarro LTD., G2508) which was interfaced to a custom-made system which automated the equilibration and analysis of seawater dissolved nitrous oxide (N2O) and methane (CH4). The combined system was deployed during two research cruises in the Atlantic Ocean, which combined covered 16,500 kms, one on a west to east transect between the United States and Europe at approximately 24°N, the second was a north to south transect which covered approximately 70° of latitude between the Tropic of Cancer and the Southern Ocean. Semi-continuous measurements using the CRDS (Approx. 73,000) were compared to discretely collected samples (n=156) which were analysed using gas chromatography (GC) with flame ionisation detection for CH4 and electron capture detection for N2O. Excellent agreement between the two approaches, though with an increase in analytical precision offered by CRDS compared to GC gives great confidence in the applicability of the CRDS system, whilst the significant (2 to 3 orders of magnitude) increase in measurement frequency offer an opportunity to greatly increase the number of dissolved N2O and CH4 data that are currently available. Whilst identifying a number of small-scale features, deployment during this study showed that whilst the surface of large areas of the Atlantic Ocean were in-balance with the overlying atmosphere with respect to N2O, the most of this region was offering a source of atmospheric CH4.
Development and external validation of a mixed-effects deep learning model to diagnose COVID-19 from CT imaging
Authors: Bridge Joshua , Meng Yanda , Zhu Wenyue , Fitzmaurice Thomas , McCann Caroline , Addison Cliff , Wang Manhui , Merritt Cristin , Franks Stu , Mackey Maria , Messenger Steve , Sun Renrong , Zhao Yitian , Zheng Yalin
Published: August 2023

Background

The automatic analysis of medical images has the potential improve diagnostic accuracy while reducing the strain on clinicians. Current methods analyzing 3D-like imaging data, such as computerized tomography imaging, often treat each image slice as individual slices. This may not be able to appropriately model the relationship between slices.

Methods

Our proposed method utilizes a mixed-effects model within the deep learning framework to model the relationship between slices. We externally validated this method on a data set taken from a different country and compared our results against other proposed methods. We evaluated the discrimination, calibration, and clinical usefulness of our model using a range of measures. Finally, we carried out a sensitivity analysis to demonstrate our methods robustness to noise and missing data.

Results

In the external geographic validation set our model showed excellent performance with an AUROC of 0.930 (95%CI: 0.914, 0.947), with a sensitivity and specificity, PPV, and NPV of 0.778 (0.720, 0.828), 0.882 (0.853, 0.908), 0.744 (0.686, 0.797), and 0.900 (0.872, 0.924) at the 0.5 probability cut-off point. Our model also maintained good calibration in the external validation dataset, while other methods showed poor calibration.

Conclusion

Deep learning can reduce stress on healthcare systems by automatically screening CT imaging for COVID-19. Our method showed improved generalizability in external validation compared to previous published methods. However, deep learning models must be robustly assessed using various performance measures and externally validated in each setting. In addition, best practice guidelines for developing and reporting predictive models are vital for the safe adoption of such models.
Mendelian randomization analysis revealed a gut microbiota–mammary axis in breast cancer
Authors: Zhang Shuwan , Zhang Wenchuan , Ren Haiyue , Xue Rui , Wang Zitong , Wang Zhe , Lv Qingjie
Published: August 2023

Background

Observational epidemiological studies suggested an association between the gut microbiota and breast cancer, but it remains unclear whether the gut microbiota causally influences the risk of breast cancer. We employed two-sample Mendelian randomization (MR) analysis to investigate this association.

Methods

We used summary statistics of the gut microbiome from a genome-wide association study (GWAS) of 18,340 individuals in the MiBioGen study. GWAS summary statistics for overall breast cancer risk and hormone receptor subtype-specific analyses were obtained from the UK Biobank and FinnGen databases, totaling 400,000 individuals. The inverse variance-weighted (IVW) MR method was used to examine the causal relationship between the gut microbiome and breast cancer and its subtypes. Sensitivity analyses were conducted using maximum likelihood, MR-Egger, and MR pleiotropic residual sums and outliers methods.

Results

The IVW estimates indicated that an increased abundance of Genus_Sellimonas is causally associated with an increased risk of ER+ breast cancer [odds ratio (OR) = 1.09, p = 1.72E−04, false discovery rate (FDR) = 0.02], whereas an increased abundance of Genus_Adlercreutzia was protective against ER+ breast cancer (OR = 0.88, p = 6.62E−04, FDR = 0.04). For Her2+ breast cancer, an increased abundance of Genus_Ruminococcus2 was associated with a decreased risk (OR = 0.77, p = 4.91E−04, FDR = 0.04), whereas an increased abundance of Genus_Erysipelatoclostridium was associated with an increased risk (OR = 1.25, p = 6.58E−04, FDR = 0.04). No evidence of heterogeneity or horizontal pleiotropy was found.

Conclusion

Our study revealed a gut microbiota–mammary axis, providing important data supporting the potential use of the gut microbiome as a candidate target for breast cancer prevention, diagnosis, and treatment.
Homemade blenderized tube feeding improves gut microbiome communities in children with enteral nutrition
Authors: Katagiri Sayaka , Ohsugi Yujin , Shiba Takahiko , Yoshimi Kanako , Nakagawa Kazuharu , Nagasawa Yuki , Uchida Aritoshi , Liu Anhao , Lin Peiya , Tsukahara Yuta , Iwata Takanori , Tohara Haruka
Published: August 2023

Enteral nutrition for children is supplied through nasogastric or gastrostomy tubes. Diet not only influences nutritional intake but also interacts with the composition and function of the gut microbiota. Homemade blenderized tube feeding has been administered to children receiving enteral nutrition, in addition to ready-made tube feeding. The purpose of this study was to evaluate the oral/gut microbial communities in children receiving enteral nutrition with or without homemade blenderized tube feeding. Among a total of 30 children, 6 receiving mainly ready-made tube feeding (RTF) and 5 receiving mainly homemade blenderized tube feeding (HBTF) were analyzed in this study. Oral and gut microbiota community profiles were evaluated through 16S rRNA sequencing of saliva and fecal samples. The α-diversity representing the number of observed features, Shannon index, and Chao1 in the gut were significantly increased in HBTF only in the gut microbiome but not in the oral microbiome. In addition, the relative abundances of the phylum Proteobacteria, class Gammaproteobacteria, and genus Escherichia-Shigella were significantly low, whereas that of the genus Ruminococcus was significantly high in the gut of children with HBTF, indicating HBTF altered the gut microbial composition and reducing health risks. Metagenome prediction showed enrichment of carbon fixation pathways in prokaryotes at oral and gut microbiomes in children receiving HBTF. In addition, more complex network structures were observed in the oral cavity and gut in the HBTF group than in the RTF group. In conclusion, HBTF not only provides satisfaction and enjoyment during meals with the family but also alters the gut microbial composition to a healthy state.
Effects of adult education on cognitive function and risk of dementia in older adults: a longitudinal analysis
Authors: Takeuchi Hikaru , Kawashima Ryuta
Published: August 2023

Introduction

Mid/late-life cognitive activities are associated with a lower rate of subsequent cognitive decline and lower subsequent dementia risk over time.

Methods

In this study, we investigated the association between adult education class participation and subsequent cognitive decline and dementia risk over time after adjusting for baseline cognitive function and genetic risk of dementia, correcting for several potential confounding variables, using a large prospective cohort data of participants from the UK Biobank study followed from 2006 to 2010.

Results

The results revealed that participation in adult education classes at baseline was associated with greater subsequent retention of fluid intelligence score. Cox proportional hazard models revealed that subjects who participated in adult education classes showed a significantly lower risk of incident dementia 5 years after baseline compared with those that did not at baseline.

Discussion

In this study, we show that participation in adult education classes preceded greater retention of subsequent fluid intelligence and a lower risk of developing dementia after 5 years: this association did not change after adjusting for cognitive function at baseline or genetic predisposition to dementia. Accordingly, participation in such classes could reduce the risk of developing dementia.
Animal-friendly behavioral testing in field studies: examples from ground squirrels
Authors: Nunes Scott
Published: August 2023

Field studies of behavior provide insight into the expression of behavior in its natural ecological context and can serve as an important complement to behavioral studies conducted in the lab under controlled conditions. In addition to naturalistic observations, behavioral testing can be an important component of field studies of behavior. This mini review evaluates a sample of behavioral testing methods in field studies to identify ways in which behavioral testing can be animal-friendly and generate ethologically relevant data. Specific examples, primarily from studies of ground squirrels, are presented to illustrate ways in which principles of animal-friendly behavioral testing can be applied to and guide testing methods. Tests conducted with animals in their natural habitat and that elicit naturally occurring behavioral responses can minimize stress and disturbance for animals, as well as disruption of the larger ecosystem, and can have high ethological validity. When animals are trapped or handled as part of a study, behavioral testing can be incorporated into handling procedures to reduce overall disturbance. When behavior is evaluated in a testing arena, the arena can be designed to resemble natural conditions to increase the ethological relevance of the test. Efforts to minimize time spent in testing arenas can also reduce disturbance to animals. Adapting a behavioral test to a species or habitat conditions can facilitate reduced disruption to subjects and increased ethological relevance of the test.
Morphological screens using aged primary adult neuronal, microglial, and astrocytic cultures to find novel neurotherapeutics
Authors: Sefiani Arthur
Published: August 2023

The average age of a patient with neurotraumatic injuries or neurodegenerative diseases has been increasing worldwide. The preclinical live animal models used for neurotrauma and neurodegenerative diseases are typically young adults, failing to represent the age of humans in the clinic. This dichotomy in age between human populations and animal models is likely to impede the understanding of the pathological mechanisms of most neurological disorders and the translation of their respective promising therapies. This lack of cohesion between animal models and patients in the clinic begins prior to in vivo testing, it starts during the in vitro drug screening phase. Conventional screening methods typically involve the use of stem cell derived neural cells, with some researchers using embryonic derived neural cells instead. These cells lack the fundamental characteristics present in aged neural cells, such as age-induced changes in process length and branching in microglia and how astrocytes respond to various insults. Various technologies and techniques have been developed recently that can help researchers use age-appropriate neural cells for their drug discovery endeavors. The use of age-appropriate neural cells during screening phases is hypothesized to significantly increase the translation rate of the hits to the geriatric patients suffering from neurotraumatic and neurodegenerative diseases.
The role of electrocochleography and the caloric test in predicting short-term recurrence of benign paroxysmal positional vertigo
Authors: Zhang Yanmei , Wang Yueqi , Zhen Zhen , Zhang Junbo , Zeng Zhengang , Zhong Zhen , Wang Quangui
Published: August 2023

Objective

The study aimed to assess the value of physiological tests for evaluating inner ear function in predicting the short-term recurrence of benign paroxysmal positional vertigo (BPPV).

Materials and methods

The clinical information of all idiopathic BPPV patients who were treated in our clinic between February 2021 and December 2022 were reviewed. All patients included in the study had completed audiology examinations including pure tone audiometry, electrocochleography (EcochG), auditory brainstem response, and vestibular function examination such as the vestibular caloric test. The relationships between the results of the above tests and short-term recurrent BPPV were analyzed.

Results

A total of 96 patients with unilateral idiopathic BPPV were included for analysis. The numbers of non-recurrent patients and recurrent patients were 57 (59.4%) and 39 (40.6%), respectively. Only the results of EcochG and the caloric test showed significant differences between non-recurrent and recurrent patients (both P < 0.05). The results of these two tests were also found to be independently predictive of short-term recurrence (both P < 0.05). The non-recurrence rate for patients with normal results in both tests reached up to 78.3%, which was significantly higher than that for patients with abnormal results in both tests, 28.6% (P < 0.05).

Conclusion

Endolymphatic hydrops and canal paresis were independent risk factors for short-term recurrent BPPV. Additional treatments should be considered to reduce the recurrence rate, including dehydration treatment and vestibular rehabilitation.
Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane
Authors: Xu Hongliang , Lv Hanyu , Chen Xin , Lian Yajun , Xing Guolan , Wang Yingzi , Hu Ruimin
Published: August 2023

Introduction

Wilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition.

Methods

A total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated.

Results

We identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study.

Discussion

Our work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.
Differential working memory function between phonological and visuospatial strategies: a magnetoencephalography study using a same visual task
Authors: Onishi Hayate , Yokosawa Koichi
Published: August 2023

Previous studies have reported that, in working memory, the processing of visuospatial information and phonological information have different neural bases. However, in these studies, memory items were presented via different modalities. Therefore, the modality in which the memory items were presented and the strategy for memorizing them were not rigorously distinguished. In the present study, we explored the neural basis of two working memory strategies. Nineteen right-handed young adults memorized seven sequential directions presented visually in a task in which the memory strategy was either visuospatial or phonological (visuospatial/phonological condition). Source amplitudes of theta-band (5–7 Hz) rhythm were estimated from magnetoencephalography during the maintenance period and further analyzed using cluster-based permutation tests. Behavioral results revealed that the accuracy rates showed no significant differences between conditions, while the reaction time in the phonological condition was significantly longer than that in the visuospatial condition. Theta activity in the phonological condition was significantly greater than that in the visuospatial condition, and the cluster in spatio-temporal matrix with p < 5% difference extended to right prefrontal regions in the early maintenance period and right occipito-parietal regions in the late maintenance period. The theta activity results did not indicate strategy-specific neural bases but did reveal the dynamics of executive function required for phonological processing. The functions seemed to move from attention control and inhibition control in the prefrontal region to inhibition of irrelevant information in the occipito-parietal region.
The interplay between macronutrients and sleep: focus on circadian and homeostatic processes
Authors: Gangitano Elena , Baxter Matthew , Voronkov Maria , Lenzi Andrea , Gnessi Lucio , Ray David
Published: August 2023

Sleep disturbances are an emerging risk factor for metabolic diseases, for which the burden is particularly worrying worldwide. The importance of sleep for metabolic health is being increasingly recognized, and not only the amount of sleep plays an important role, but also its quality. In this review, we studied the evidence in the literature on macronutrients and their influence on sleep, focusing on the mechanisms that may lay behind this interaction. In particular, we focused on the effects of macronutrients on circadian and homeostatic processes of sleep in preclinical models, and reviewed the evidence of clinical studies in humans. Given the importance of sleep for health, and the role of circadian biology in healthy sleep, it is important to understand how macronutrients regulate circadian clocks and sleep homeostasis.
Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation
Authors: Janilkarn-Urena Isis , Idrissova Alina , Zhang Mindy , VanDreal Masha , Sanghavi Neysa , Skinner Samantha G. , Cheng Sydney , Zhang Zeyu , Watanabe Junji , Asatryan Liana , Cadenas Enrique , Davies Daryl L.
Published: August 2023

Introduction

Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity.

Methods

Female c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant.

Results

Dihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17.

Discussion

Dihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology.
Anti-U1RNP-70kD-positive case of neonatal lupus presenting with seizure and incomplete heart block: a case report and literature review
Authors: Alfalasi Maryam , ElGhazali Gehad , Fathalla Waseem , Khawaja Khulood
Published: August 2023

Neonatal lupus erythematosus (NLE) is an autoimmune disease caused by the transplacental passage of anti-Ro/SS-A and anti-La/SS-B. This can be less commonly seen with U1-ribonucleoprotein (U1RNP). Our patient is a 7-day-old male, who first presented with seizures. In addition, during an electroencephalogram, he was found to have an irregular heart rhythm. Looking further into the history, we found that the mother was aware that she had systemic lupus erythematosus (SLE). However, she had not been followed up with a rheumatologist. The workup for NLE found a negative anti-Ro/SS-A and anti-La/SS-B, with a positive U1RNP-70kD. U1RNP-70kD is a diagnostic test for mixed connective tissue disease in adults, but no research has been done on its significance in NLE. Despite having SLE, the infant’s mother did not receive surveillance during her pregnancy, as the current guidelines are tailored for mothers with anti-Ro/SS-A and anti-La/SS-B. As a result, this calls for the extension of these guidelines to include the U1RNP-70kD antibody. In this case, the 70kD subtype of U1RNP was positive, which may have had a role to play in this unusual presentation. However, further research is needed to improve the care of mothers and babies with U1RNP-70kD.
Bioanalytical method validation and application to a phase 1, double-blind, randomized pharmacokinetic trial of a standardized Centella asiatica (L.) Urban water extract product in healthy older adults
Authors: Wright Kirsten M. , Bollen Melissa , David Jason , Mepham Bridgette , Alcázar Magaña Armando , McClure Christine , Maier Claudia S. , Quinn Joseph F. , Soumyanath Amala
Published: August 2023

Introduction:Centella asiatica is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that C. asiatica aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from C. asiatica in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults.

Methods: High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used for detecting triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. Validation parameters including linearity, precision, accuracy, recovery and thermal stability were evaluated. The method was applied to a Phase I, randomized, double-blind, crossover trial of two doses (2 or 4 g) of a standardized C. asiatica water extract product (CAP) in eight healthy older adults. Pharmacokinetic parameters were measured over a 12-h post administration period and acute safety was assessed.

Results: The method satisfied US Food & Drug Administration criteria for linearity and recovery of the analytes of interest in human plasma and urine. The method also satisfied criteria for precision and accuracy at medium and high concentrations. Single administration of 2 and 4 g of CAP was well tolerated and safe in healthy older adults. The parent triterpene glycosides, asiaticoside and madecassoside, were not detected in plasma and in minimal amounts in urinary excretion analyses, while the aglycones, asiatic acid and madecassic acid, showed readily detectable pharmacokinetic profiles. Similarly, the di-caffeoylquinic acids and mono-caffeoylquinic acids were detected in low quantities, while their putative metabolites showed readily detectable pharmacokinetic profiles and urinary excretion.

Discussion: This method was able to identify and calculate the concentration of triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. The oral absorption of these key compounds from CAP, and its acute safety in healthy older adults, support the use of this C. asiatica product in future clinical trials.
Multisystem inflammatory syndrome drug treatment in countries with different income profiles: a scoping review
Authors: Nagem Lopes Luis Phillipe , da Cunha Lidiane Gomes , Silva Alice Ramos Oliveira , Land Marcelo Gerardin Poirot , Fonseca Adriana Rodrigues , Lopes Luciane Cruz , Lima Elisangela Costa
Published: August 2023

Objective: The purpose of this study was to map and describe the studies that have investigated therapeutic alternatives for the management of paediatric multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Considering the origin of the studies performed (low-, middle- and high-income countries), a systematic scoping review was conducted with primary studies that reported the use of medications for the treatment of patients with MIS-C.

Sources: The searches were performed in MEDLINE, Embase, Lilacs, Epistemonikos, CINAHL, and CENTRAL, in the grey literature (theses and dissertations from CAPES, ProQuest, and PROSPERO) and in clinical trial databases until May 2022. The selection and extraction of studies were performed independently by two reviewers.

Summary of the findings: A total of 173 studies were included, most of which were published as case reports or series. No randomized controlled clinical trials (RCTs) were identified. The investigated drugs were immunoglobulins, glucocorticoids, monoclonal antibodies, anticoagulants, and antiplatelet agents.

Conclusion: The dosages, when reported, were heterogeneous among the studies. The ethnicity and comorbidity of the participants were poorly reported. Monoclonal antibodies, drugs with higher costs, were mostly described in studies of high-income countries.