bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual dimorphism in the molecular mechanisms of insulin resistance during a critical developmental window in Wistar rats
Authors: Ortiz-Huidobro Rosa Isela , Larqué Carlos , Velasco Myrian , Chávez-Maldonado Juan Pablo , Sabido Jean , Sanchez-Zamora Yuriko Itzel , Hiriart Marcia 
Published: October 2022

AbstractBackgroundInsulin resistance (IR) is a condition in which the response of organs to insulin is impaired. IR is an early marker of metabolic dysfunction. However, IR also appears in physiological contexts during critical developmental windows. The molecular mechanisms of physiological IR are largely unknown in both sexes. Sexual dimorphism in insulin sensitivity is observed since early stages of development. We propose that during periods of accelerated growth, such as around weaning, at postnatal day 20 (p20) in rats, the kinase S6K1 is overactivated and induces impairment of insulin signaling in its target organs. This work aimed to characterize IR at p20, determine its underlying mechanisms, and identify whether sexual dimorphism in physiological IR occurs during this stage.MethodsWe determined systemic insulin sensitivity through insulin tolerance tests, glucose tolerance tests, and blood glucose and insulin levels under fasting and fed conditions at p20 and adult male and femaleWistarrats. Furthermore, we quantified levels of S6K1 phosphorylated at threonine 389 (T389) (active form) and its target IRS1 phosphorylated at serine 1101 (S1101) (inhibited form). In addition, we assessed insulin signal transduction by measuring levels of Akt phosphorylated at serine 473 (S473) (active form) in white adipose tissue and skeletal muscle through western blot. Finally, we determined the presence and function of GLUT4 in the plasma membrane by measuring the glucose uptake of adipocytes. Results were compared using two-way ANOVA (With age and sex as factors) and one-way ANOVA with post hoc Tukey’s tests or t-student test in each corresponding case. Statistical significance was considered forPvalues < 0.05.ResultsWe found that both male and female p20 rats have elevated levels of glucose and insulin, low systemic insulin sensitivity, and glucose intolerance. We identified sex- and tissue-related differences in the activation of insulin signaling proteins in p20 rats compared to adult rats.ConclusionsMale and female p20 rats present physiological insulin resistance with differences in the protein activation of insulin signaling. This suggests that S6K1 overactivation and the resulting IRS1 inhibition by phosphorylation at S1101 may modulate to insulin sensitivity in a sex- and tissue-specific manner.
Tumor necrosis factor inhibitors for pediatric patients with SAPHO syndrome associated with acne conglobata
Authors: Liu Shengyan , Wu Xia , Cao Yihan , Li Zhaohui , Liu Yuchen , Ma Mingwei , Li Chen 
Published: October 2022

AbstractSynovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.
Thymofibrolipoma: a case report and review of the literature
Authors: Jokoji Ryu , Tomita Emiko 
Published: October 2022

Abstract
Background
Thymofibrolipoma has been described as a variant of thymolipoma. To date, 3 cases have been reported, and the lesion have been described to consist of extensive areas of collagenous tissue interspersed with islands of mature adipose tissue and strands of thymic tissue.

Case presentation
A 43-year-old woman had an anterior mediastinal tumor. Macroscopically, the cut surface of the tumor was composed of a yellowish lipomatous component and a uniform whitish fibrous component with elastic stiffness. Microscopically, the tumor was composed of collagenous fibrous tissue with sparse spindle cells, mature adipocytes and strands or islands of thymic tissue. The spindle cells in the fibrous tissue had monoallelic deletion of the 13q14 region and corresponding loss of RB1 and FOXO1A protein expression.

Conclusions
This case report may strengthen the hypothesis that thymofibrolipoma is a neoplastic lesion and a variant of thymolipoma and that thymofibrolipoma and lipofibroadenoma are different names for the same lesion. The name “lipofibroadenoma” was given to the lesion because of its histological resemblance to fibroadenoma of the mammary gland. However, this name does not reflect the pathogenesis of this lesion, and the name “thymofibrolipoma” would be preferable. It will be necessary to discuss whether lipofibroadenoma should be listed as an independent entity in the WHO classification.
Establishment of a bipedal rat model of lumbar facet joint osteoarthritis using intraarticular injection of urinary plasminogen activator
Authors: Yang Di , Hu Wei , Li Hao , Shao Yin-chu , Shan Ji-chun , Xiong Xu , Shuang Feng 
Published: October 2022

Abstract
Background
Previous studies have demonstrated that by injecting uPA into the lumbar facet joints (LFJ) of normal rats, a rat LFJOA animal model can be successfully established. However, there is no evidence that intraarticular injection of uPA can induce or much serious osteoarthritis in bipedal rats, which biomechanics is much more similar to human than normal rats. To investigate whether intraarticular injection of urinary plasminogen activator (uPA) can induce LFJOA and low back pain symptoms in bipedal rats.

Methods
An experimental study on the construction of a modified animal model of lumbar facet joints osteoarthritis (LFJOA) which biomechanics is similar to human. Sprague–Dawley rats were treated with intraarticular injection of uPA in the L5–L6 facet joints (uPA group, n = 15) or saline (saline group, n = 15). The forelimbs of both two group rats were amputated. Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin–eosin staining, and immunohistochemical examination of the LFJ was performed.

Results
The saline group rats have not demonstrated significant osteoarthritis in rats LFJ after surgery. The uPA group has not been induced significantly higher mechanical and thermal hyperalgesia in comparison with the saline group. But intraarticular injection of uPA in biped rats induced significantly stronger articular cartilage damage, synovitis, and proliferation of synovial cells in the LFJ. Inflammatory factors such as iNOS, IL-1β, and TNF-a were more significantly expressed in bipedal rat injected with uPA (p < 0.05).

Conclusions
Intraarticular injection of uPA can induce LFJOA in bipedal rats, while upright posture does not induce osteoarthritis in rats LFJ in the short term.
Transcriptomic profiling of sporadic Alzheimer’s disease patients
Authors: Caldwell Andrew B. , Anantharaman Balaji G. , Ramachandran Srinivasan , Nguyen Phuong , Liu Qing , Trinh Ivy , Galasko Douglas R. , Desplats Paula A. , Wagner Steven L. , Subramaniam Shankar 
Published: October 2022

AbstractAlzheimer’s disease (AD) manifested before age 65 is commonly referred to as early-onset AD (EOAD) (Reitz et al. Neurol Genet. 2020;6:e512). While the majority (> 90%) of EOAD cases are not caused by autosomal-dominant mutations in PSEN1, PSEN2, and APP, they do have a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%) (Wingo et al. Arch Neurol. 2012;69:59–64, Fulton-Howard et al. Neurobiol Aging. 2021;99:101.e1–101.e9). Although the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). This heterogeneity, leading to temporally distinct age at onset (AAO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes (Caldwell et al. Sci Adv Am Assoc Adv Sci. 2020;6:eaba5933, Mertens et al. Cell Stem Cell. 2021;28:1533–1548.e6, Caldwell et al. Alzheimers Demen. 2022). Further, analyses of large postmortem brain cohorts demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected and, therefore, may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology (Haroutunian et al. Neurobiol Aging. 2009;30:561–73). To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD) using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AAO may not directly correlate with the identity and severity of AD endotypes.
Parents, health professionals and footwear stakeholders' beliefs on the importance of different features of young children's footwear: a qualitative study
Authors: Williams Cylie M. , Banwell Helen A. , Paterson Kade L. , Gobbi Katherine , Burton Sam , Hill Matthew , Harber Emma , Morrison Stewart C. 
Published: October 2022

AbstractBackgroundA small but building pool of evidence of the impact of footwear on children's function means understanding the different beliefs of stakeholders about footwear key features and flexibility is critical for translation into recommendations and to support parents and caregivers in purchasing footwear for their children. Therefore, this research aimed to describe how different stakeholders (health professionals, parents, and footwear industry representatives) described the importance of flexibility and other footwear features for young children.MethodsThis qualitative study was nested within an international modified Delphi online survey. Participants responded to open‐ended questions about footwear component flexibility and asked if and why flexibility in these areas were important. Participants also described any other important footwear features. Inductive thematic analysis was used to generate themes.ResultsThere were 121 responses from three stakeholder groups including health professionals (n = 90), parents of young children (n = 26) and footwear industry representatives (n = 5). Overarching themes described by participants included developmental impacts of footwear, therapeutic impact and how footwear may play a role in function.ConclusionThere were key differences in how stakeholders viewed footwear and any perceived benefits of footwear components, much of which was not backed with empirical evidence. It was also identified that health professionals are using footwear within treatment recommendations. This work highlights the importance of understanding circumstances in which footwear may have a therapeutic impact or be the first line of treatment for children with complex foot needs. This is the first step in developing contemporary footwear recommendations for parents and caregivers.
A low-cost genomics workflow enables isolate screening and strain-level analyses within microbiomes
Authors: Sanders Jon G. , Yan Weiwei , Mjungu Deus , Lonsdorf Elizabeth V. , Hart John A. , Sanz Crickette M. , Morgan David B. , Peeters Martine , Hahn Beatrice H. , Moeller Andrew H. 
Published: October 2022

Abstract
Earth’s environments harbor complex consortia of microbes that affect processes ranging from host health to biogeochemical cycles. Understanding their evolution and function is limited by an inability to isolate genomes in a high-throughput manner. Here, we present a workflow for bacterial whole-genome sequencing using open-source labware and the OpenTrons robotics platform, reducing costs to approximately $10 per genome. We assess genomic diversity within 45 gut bacterial species from wild-living chimpanzees and bonobos. We quantify intraspecific genomic diversity and reveal divergence of homologous plasmids between hosts. This enables population genetic analyses of bacterial strains not currently possible with metagenomic data alone.
Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases
Authors: Lee Seonghyun , Lee Hyunji , Baek Gayoung , Namgung Eunji , Park Joo Min , Kim Sanghun , Hong Seongho , Kim Jin-Soo 
Published: October 2022

AbstractWe present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.
Effect of intermittent fasting 5:2 on body composition and nutritional intake among employees with obesity in Jakarta: a randomized clinical trial
Authors: Witjaksono Fiastuti , Prafiantini Erfi , Rahmawati Anni 
Published: October 2022

Abstract
Objective
This study aimed to determine the effect of intermittent fasting 5:2 on body composition in employees with obesity in Jakarta.

Results
Fifty participants were included; 25 were allocated to the fasting group and 25 to the control group. There was no significant change in fat mass, fat-free mass, skeletal muscle, and BMI (p > 0.05). Significant in-group changes were observed in body weight (p = 0.023) and BMI (p = 0.018) in the fasting group. Dietary intake was similar before and during the intervention. The reduction in macronutrient intake resulted in a statistically significant difference in carbohydrate, protein, and fat intake in the two groups (p < 0.05). Intermittent fasting 5:2 results in weight loss but does not affect fat mass and fat-free mass reductions. None of the between-group differences were clinically relevant.

Trial registration:
ClinicalTrials.gov with ID: NCT04319133 registered on 24 March 2020.
The important role of NLRP6 inflammasome in Pasteurella multocida infection
Authors: Wu Xingping , Zeng Zheng , Tian Hongliang , Peng Lianci , Xu Dongyi , Wang Yu , Ye Chao , Peng Yuanyi , Fang Rendong 
Published: October 2022

AbstractPasteurella multocida (P. multocida) can cause severe respiratory disease in cattle, resulting in high mortality and morbidity. Inflammasomes are multiprotein complexes in the cytoplasm that recognize pathogens and play an important role in the host defense against microbial infection. In this study, the mechanism of P. multocida-induced NLRP6 inflammasome activation was investigated in vitro and in vivo. Firstly, P. multocida induced severe inflammation with a large number of inflammatory cells infiltrating the lungs of WT and Nlrp6−/− mice. Nlrp6−/− mice were more susceptible to P. multocida infection and they had more bacterial burden in the lungs. Then, the recruitment of macrophages and neutrophils in the lungs was investigated and the results show that the number of immune cells was significantly decreased in Nlrp6−/− mice. Subsequently, NLRP6 was shown to regulate P. multocida-induced inflammatory cytokine secretion including IL-1β and IL-6 both in vivo and in vitro while TNF-α secretion was not altered. Moreover, NLRP6 was found to mediate caspase-1 activation and ASC oligomerization, resulting in IL-1β secretion. Furthermore, NLRP6 inflammasome mediated the gene expression of chemokines including CXCL1, CXCL2 and CXCR2 which drive the activation of NLRP3 inflammasomes. Finally, NLRP3 protein expression was detected to be abrogated in P. multocida-infected Nlrp6−/− macrophages, indicating the synergic effect of NLRP6 and NLRP3. Our study demonstrates that NLRP6 inflammasome plays an important role in the host against P. multocida infection and contributes to the development of immune therapeutics against P. multocida.
RNA binding protein HuR protects against NAFLD by suppressing long noncoding RNA H19 expression
Authors: Wang Yanyan , Tai Yun-Ling , Way Grayson , Zeng Jing , Zhao Derrick , Su Lianyong , Jiang Xixian , Jackson Kaitlyn G. , Wang Xuan , Gurley Emily C. , Liu Jinze , Liu Jinpeng , Chen Weidong , Wang Xiang-Yang , Sanyal Arun J. , Hylemon Phillip B. , Zhou Huiping 
Published: October 2022

Abstract
Background
NAFLD has become the most common chronic liver disease worldwide. Human antigen R (HuR), an RNA-binding protein, is an important post-transcriptional regulator. HuR has been reported as a key player in regulating lipid homeostasis in the liver and adipose tissues by using tissue-specific HuR knockout mice. However, the underlying mechanism by which hepatocyte-specific HuR regulates hepatic lipid metabolism under metabolic stress remains unclear and is the focus of this study.

Methods
Hepatocyte-specific HuR deficient mice (HuRhKO) and age-/gender-matched control mice, as well as long-noncoding RNA H19 knockout mice (H19−/−), were fed a Western Diet plus sugar water (WDSW). Hepatic lipid accumulation, inflammation and fibrosis were examined by histology, RNA transcriptome analysis, qRT–PCR, and Western blot analysis. Bile acid composition was measured using LC–MS/MS.

Results
Hepatocyte-specific deletion of HuR not only significantly increased hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also markedly induced inflammation by increasing immune cell infiltration and neutrophil activation under metabolic stress. In addition, hepatic deficiency of HuR disrupted bile acid homeostasis and enhanced liver fibrosis. Mechanistically, HuR is a repressor of H19 expression. Analysis of a recently published dataset (GSE143358) identified H19 as the top-upregulated gene in liver-specific HuR knockout mice. Similarly, hepatocyte-specific deficiency of HuR dramatically induced the expression of H19 and sphingosine-1 phosphate receptor 2 (S1PR2), but reduced the expression of sphingosine kinase 2 (SphK2). WDSW-induced hepatic lipid accumulation was alleviated in H19−/− mice. Furthermore, the downregulation of H19 alleviated WDSW-induced NAFLD in HuRhKO mice.

Conclusions
HuR not only functions as an RNA binding protein to modulate post-transcriptional gene expression but also regulates H19 promoter activity. Hepatic HuR is an important regulator of hepatic lipid metabolism via modulating H19 expression.
Surface fungal diversity and several mycotoxin-related genes’ expression profiles during the Lunar Palace 365 experiment
Authors: Yang Jianlou , Hao Zikai , Zhang Lantao , Fu Yuming , Liu Hong 
Published: October 2022

AbstractBackgroundChinese Lunar Palace 1 (LP1) is a ground-based bio-regenerative life support system (BLSS) test bed integrating highly efficient plant cultivation, animal protein production, urine nitrogen recycling, and bioconversion of solid waste. To date, there has been no molecular method-based detailed investigation of the fungal community and mycotoxin potential in BLSS habitats. To ensure safe BLSS design for actual space missions, we analyzed the LP1 surface mycobiome and mycotoxin potential during the Lunar Palace 365 project through internal transcribed spacer region 1 (ITS1) amplicon sequencing and quantitative polymerase chain reaction (qPCR) with primers specific foridh,ver1,nor1,tri5, andITS1.ResultsThe LP1 system exhibited significant differences in fungal community diversity compared to other confined habitats, with higher fungal alpha diversity and different community structures. Significant differences existed in the surface fungal communities of the LP1 habitat due to the presence of different occupant groups. However, there was no significant difference between fungal communities in the plant cabin with various occupants. Source tracker analysis shows that most of the surface fungi in LP1 originated from plants. Regardless of differences in occupants or location, there were no significant differences in mycotoxin gene copy number.ConclusionsOur study reveals that plants are the most crucial source of the surface fungal microbiome; however, occupant turnover can induce significant perturbations in the surface fungal community in a BLSS. Growing plants reduced fungal fluctuations, maintaining a healthy balance in the surface fungal microbiome and mycotoxin potential. Moreover, our study provides data important to (i) future risk considerations in crewed space missions with long-term residency, (ii) an optimized design and planning of a space mission that incorporates crew shifts and plant growth, and (iii) the expansion of our knowledge of indoor fungal communities with plant growth, which is essential to maintain safe working and living environments.
Metaverse through the prism of power and addiction: what will happen when the virtual world becomes more attractive than reality?
Authors: Bojic Ljubisa 
Published: October 2022

AbstractNew technologies are emerging at a fast pace without being properly analyzed in terms of their social impact or adequately regulated by societies. One of the biggest potentially disruptive technologies for the future is the metaverse, or the new Internet, which is being developed by leading tech companies. The idea is to create a virtual reality universe that would allow people to meet, socialize, work, play, entertain, and create.Methods coming from future studies are used to analyze expectations and narrative building around the metaverse. Additionally, it is examined how metaverse could shape the future relations of power and levels of media addiction in the society.Hype and disappointment dynamics created after the video presentation of meta’s CEO Mark Zuckerberg have been found to affect the present, especially in terms of certainty and designability. This idea is supported by a variety of data, including search engine n-grams, trends in the diffusion of NFT technology, indications of investment interest, stock value statistics, and so on. It has been found that discourse in the mentioned presentation of the metaverse contains elements of optimism, epochalism, and inventibility, which corresponds to the concept of future essentialism.On the other hand, power relations in society, inquired through the prism of classical theorists, indicate that current trends in the concentration of power among Big Tech could expand even more if the metaverse becomes mainstream. Technology deployed by the metaverse may create an attractive environment that would mimic direct reality and further stimulate media addiction in society.It is proposed that future inquiries examine how virtual reality affects the psychology of individuals and groups, their creative capacity, and imagination. Also, virtual identity as a human right and recommender systems as a public good need to be considered in future theoretical and empirical endeavors.