bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal dominant STAT6 gain of function causes severe atopy associated with lymphoma
Authors: Minskaia* Ekaterina , Maimaris* Jesmeen , Jenkins Persephone , Albuquerque Adriana S. , Grace Richard , Moreira Fernando , Grimbacher Bodo , Morris Emma C. , Burns Siobhan O. 
Published: October 2022

Abstract
The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis.
Synergistic effect of sulfonation followed by precipitation of amorphous calcium phosphate on the bone-bonding strength of carbon-fiber-reinforced polyetheretherketone
Authors: Takaoka Yusuke , Fujibayashi Shunsuke , Yabutsuka Takeshi , Yamane Yuya , Ishizaki Chihiro , Goto Koji , Otsuki Bungo , Kawai Toshiyuki , Shimizu Takayoshi , Okuzu Yaichiro , Masamoto Kazutaka , Shimizu Yu , Hayashi Makoto , Ikeda Norimasa , Matsuda Shuichi 
Published: October 2022

Abstract
Sulfonation and applications of amorphous calcium phosphate are known to make polyetheretherketone (PEEK) bioactive. Sulfonation followed by precipitation of amorphous calcium phosphate (AN-treatment) may provide PEEK with further bone-bonding strength. Herein, we prepared a carbon-fiber-reinforced PEEK (CPEEK) with similar tensile strength to cortical bone and a CPEEK subjected to AN-treatment (CPEEK-AN). The effect of AN-treatment on the bone-bonding strength generated at the interface between the rabbit's tibia and a base material was investigated using a detaching test at two time-points (4 and 8 weeks). At 4 weeks, the strength of CPEEK-AN was significantly higher than that of CPEEK due to the direct bonding between the interfaces. Between 4 and 8 weeks, the different bone forming processes showed that, with CPEEK-AN, bone consolidation was achieved, thus improving bone-bonding strength. In contrast, with CPEEK, a new bone was absorbed mainly on the interface, leading to poor strength. These observations were supported by an in vitro study, which showed that pre-osteoblast on CPEEK-AN caused earlier maturation and mineralization of the extracellular matrix than on CPEEK. Consequently, AN-treatment, comprising a combination of two efficient treatments, generated a synergetic effect on the bonding strength of CPEEK.
Effects of Corn oligopeptide on Dexamethasone-induced muscle atrophy in Sprague-Dawley rats
Authors: Wang Yunfeng , Yan Jiuming , Shi Lei , Zhou Zhengming , Guo Jiankui , Wei Yaoyao , Hu Wen 
Published: October 2022

Abstract
Corn oligopeptide (COP) derived from corn gluten meal (CGM) was proved to possess plenty of biological properties. However, there is no scientific evidence to support that COP can ameliorate muscle atrophy. To find a new therapeutic nutritional substrate of muscle atrophy, we investigated the anti-myopathy effects of COP in DEX-inducted rat muscle atrophy model and tried to explore the underlying mechanisms. Co-administration of COP (2.0g/kg.bw) with DEX for 5 weeks reversed DEX-induced reduction in gastrocnemius (Gas) and plantaris (Pla) muscles weight, grip strength, exercise tolerance and myofiber cross sectional area (CSA) of soleus (Sol), up-regulated the protein levels of Phospho-Akt and mTOR that are closely relate to protein synthesis, and down-regulated the expression of FoxO3a, NF-κBp65, Atrogin-1, MuRF-1, LC3 and ULK1 that are the key components of Ubiquitin–proteasome system and Autophagy that activate proteolysis. In addition, according to muscles weight, grip strength, exercise tolerance changing over experiment time, we found the three indexes were all improved at 3rd week. Therefore, we conclude that the optimal duration for COP to improve DEX-induced muscle atrophy might be 3 weeks, and mechanistically, COP activates protein synthesis through Akt/mTOR pathway, while inhibits proteolysis by inactivating the expression of Ubiquitin proteasome system (UPS) and Autophagy.
Beneficial Effects of Anti-Apolipoprotein A-2 on an Animal Model for Coronary Arteritis in Kawasaki Disease
Authors: Ito Fuyu , Oharaseki Toshiaki , Tsukui Daisuke , Kimura Yoshitaka , Yanagida Tamiko , Kishi Fukuko , Yamakawa Yoshio , Kameoka Yosuke , Suzuki Shoichi , Uno Kazuko , Suzuki Osamu , Miura Noriko N , Ohno Naohito , Takahashi Kei , Kono Hajime , Suzuki Kazuo 
Published: October 2022

Abstract
Background
Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required.
Melatonin regulates the mitogen-activated protein kinase ( MAPK ) pathway via the circMPP5-miR-211-MAPK3 axis to induce secondary hair follicle differentiation and development in newborn Cashmere goat kids
Authors: Diao Xiaogao , Yao Lingyun , Duan Tao , Qin Jiaxin , He Liwen , Zhang Wei 
Published: October 2022

Abstract
Background
The quality and yield of Cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of Cashmere goats. The higher the density of secondary hair follicles, the higher the quality and yield of Cashmere from the fleece. Development of secondary hair follicles commences in the embryonic stage of life and is completed six months after birth. Preliminary experimental results from our laboratory showed that melatonin (MT) treatment of goat kids after their birth could increase the density of secondary hair follicles and, thus, improve the subsequent yield and quality of Cashmere. These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein, and from a reduction in apoptosis. The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.
Results
MT had no adverse effect on the growth performance of Cashmere kids but significantly improved the character of the secondary hair follicles and the quality of Cashmere, and this dominant effect continued to the second year. Melatonin promotes the proliferation of secondary hair follicle cells at an early age. Secondary hair follicles in the MT group formation was earlier than in the control group in the second year. The genome-wide data results involved KEGG analysis of 1044 DEmRNAs, 91 DElncRNAs, 1054 DEcircRNAs, and 61 DEmiRNAs which revealed that the MAPK signaling pathway is involved in the development of secondary hair follicles, with key genes (FGF2, FGF21, FGFR3, MAPK3 (ERK1)) being up-regulated and expressed. We also found that the circMPP5 could combine with miR-211 and regulate the expression of MAPK3.
Conclusions
We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5-miR-211-MAPK3 axis to induce the differentiation and proliferation of secondary hair follicle cells. In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells. Collectively, these events increase the numbers of secondary hair follicles, thus improving the production of Cashmere from these goats.
Design -assisted spectrofluorometric method utilizing carbon quantum dots for the quantitation of some calcium channel blockers
Authors: roshdy aya , Salam Randa Abdel , Hadad Ghada , Belal Fathallah , Elmansi Heba 
Published: October 2022

Abstract
Based on their reaction with highly fluorescent carbon quantum dots (CQDts), a precise and reliable spectrofluorometric approach was developed for the determination of three calcium channel blockers. The studied drugs are: lercanidipine, nimodipine and nifedipine. (CQDts) were produced using a one-step hydrothermal method with ascorbic acid as the carbon source. The produced CQDts were capped by alcohol to create yellow emitters displaying a high fluorescence emission at 524 nm when excited at 325 nm. The fluorescence intensity of CQDts was noticeably quenched by each of the three calcium channel blockers. The relation between their concentrations and fluorescence quenching is linear over the concentration range of 0.5–20 µg/mL for each of the three drugs. Full factorial design was used to optimize the effect of variable factors. Therefore, under optimum experimental design conditions, the detection limits for lercanidipine, nimodipine, and nifedipine were 0.11, 0.10, and 0.12 µg/mL, respectively. The LOQ were 0.33, 0.30 and 0.37 µg/mL respectively. The quenching of fluorescent CQDts occurred through inner filter effect (IFE) for nimodipine, while it was mixed with dynamic quenching for lercanidipine and nifedipine. The proposed method was effectively used to determine the cited drugs in their pharmaceutical products and had an acceptable level of precision. The selectivity of the CQDts system towards the studied drugs was examined indicating no interference from interfering species.
Computational Study of the Mechanical Behavior of the Astrocyte Network and Axonal Compartments in the Mouse Optic Nerve Head
Authors: Ling Yik Tung Tracy , Korneva Arina , Quigley Harry , Nguyen Thao 
Published: October 2022

Abstract
Glaucoma is a blinding disease characterized by the degeneration of the retinal ganglion cell (RGC) axons at the optic nerve head (ONH). A major risk factor for glaucoma is the intraocular pressure (IOP). However, it is currently impossible to measure the IOP-induced mechanical responses in the axons of the ONH. The objective of this study was to develop a computational model to estimate the IOP-induced strains and stresses in the axonal compartments in the mouse astrocytic lamina (AL) of the ONH, and to investigate the effect of the structural features on the mechanical behavior.
We developed experimentally-informed finite element (FE) models of six mouse AL to investigate the effect of structure on the stress and strain response of the astrocyte network and axonal compartments to pressure elevation. The specimen-specific geometries of the FE models were reconstructed from confocal fluorescent images of cryosections of the mouse AL acquired in a previous study that measured the structural features of the astrocytic processes and axonal compartments. The displacement fields obtained from digital volume correlation in prior inflation tests of the mouse AL were used to determine the in-plane boundary conditions of the FE models. We applied a machine learning algorithm, Gaussian process regression, to analyze the effects of the structural features on the strains and stresses simulated for each axonal compartment.
The axonal compartments experienced, on average, 5 times higher maximum principal strain but 1800 times lower maximum principal stress compared to that experienced by the astrocyte processes. The mechanical responses in the axonal compartments were most sensitive to variations in the area and orientation of the axonal compartments. Larger axonal compartments that were more vertically aligned, closer to the AL center, and with lower local actin area fraction had higher strains. Understanding the factors affecting the deformation and stress state in the axonal compartments will provide insights into mechanisms of glaucomatous axonal damage.
Ho:YAG laser at 2097 nm pumped by a narrow linewidth tunable 1.91 μm laser
Authors: Tian Juntao , Zhao Lili , Li Zhiyong , Bian Jintian , Ye Qing , Wang Hai , Tan Rongqing 
Published: October 2022

Abstract
This study presents a high efficiency Ho:YAG laser based on a narrow linewidth tunable 1.91 µm laser. A tunable Tm:YLF laser is the pump source and the wavelength continuous tunability ranges from 1906.04 to 1908.83 nm, corresponding to a linewidth of less than 0.41 nm. The tunable Tm:YLF laser is achieved by changing the operating temperature of the VBG. The output power of the Ho:YAG laser is between 21.04–23.53 W and the slope efficiency is between 64.08% − 68.26% at the pump power of 39.8 W. The output power and slope efficiency corresponding to the pump wavelength of 1907.36 nm are 23.53 W and 68.26%, respectively. This study illustrates that fine-tuning the pump wavelength is an effective way to improve the slope efficiency and output power of the Ho:YAG laser at room temperature.
Transcriptomic and enzymatic analysis reveals the roles of glutamate dehydrogenase in Corynebacterium glutamicum
Authors: Ge Fanglan , Sun Jingkun , Ren Yao , He Bing , Li Jiao , Yang Sen , Li Wei 
Published: October 2022

Abstract
Glutamate dehydrogenase (Gdh), catalyzing the reversible conversion between 2-oxoglutarate and glutamate, plays an important role in the connection of nitrogen and carbon metabolism. Yet little is known about these enzymes in the amino acid-manufacturing Corynebacterium glutamicum. In the present study, we firstly identified the enzymatic characteristics of two Gdhs (GdhA and GdhB). The results showed that both GdhA and GdhB prefers NADPH as a coenzyme and have higher affinity for 2-OG than glutamate. The growth characteristics of gdhAΔ mutant and gdhBΔ mutant, gdhABΔ mutant showed GdhA serves as the main conduit for ammonium assimilation, and GdhB is the main glutamate- metabolizing enzyme in C. glutamicum. The full-genome transcriptomic analysis was used to investigate physiological response of C. glutamicum to the glutamate as nitrogen source, and gdh deletion. The results showed that the nitrogen starvation response was elicited when glutamine served as the sole nitrogen source. gdhAΔBΔ double deletion trigger a partially deregulated nitrogen starvation response, in which genes involved in nitrogen assimilation showed obviously up-regulated in a certain extent. On the other hand, the genes of phosphotransferase system (PTS) and glycolysis pathway, most genes in pentose phosphate pathway were significantly up-regulated, indicating that gdh deficiency initiated the enhancement of the absorption and metabolism of carbon sources. we believed that our results in this study will give new insights on the molecular mechanism of Gdh activity cross-talks with carbon and nitrogen metabolism, also setting a new background for further flux redistribution applied research of biotechnological interest.
ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis
Authors: De Vitis Claudia , Battaglia Anna Martina , Pallocca Matteo , Santamaria Gianluca , Mimmi Maria Chiara , Sacco Alessandro , De Nicola Francesca , Gaspari Marco , Salvati Valentina , Ascenzi Francesca , Bruschini Sara , Esposito Antonella , Ricci Giulia , Sperandio Eleonora , Prestagiacomo Licia Elvira , Cavaliere Rosy , Vecchione Andrea , Ricci Alberto , Sciacchitano Salvatore , Salerno Gerardo , French Deborah , Aversa Ilenia , Cereda Cristina , Fanciulli Maurizio , Chiaradonna Ferdinando , Cuda Giovanni , Costanzo Francesco , Ciliberto Gennaro , Mancini Rita , Biamonte Flavia 
Published: October 2022

Abstract
Background
Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions.
Methods
3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2D to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines.
Results
We found that the transition from 2D to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production and cell viability. Furthermore, both the number and size of spheroids produced by H460, HCC827, MCF7, and T47D cell lines were significantly reduced upon ALDOC and ENO2 knockdown.
Conclusions
Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid regardless of the tumor type and nutrient environmental availability, thus suggesting the possible general involvement of this mechanism in cancer metastasis. The pan-cancer validation of this vulnerability could potentially help to slow or prevent cancer progression.
Sensor-based assessment of social isolation incommunity-dwelling older adults: A scopingreview
Authors: Khan Shehroz S. , Gu Tiancheng , Spinelli Lauren , Wang Rosalie H. 
Published: October 2022

Abstract
Social isolation (SI) is a state of low social interaction with peers associated with various adverse healthconsequences in older adults living in the community. SI is most often assessed through retrospective self-reports, which can be prone to recall or self-report biases and influenced by stigma. Ambient and wearable sensors have been explored to objectively assess SI based on interactions of a person within the environment and physiological data. However, because this field is in its infancy, there is a lack of clarity regarding the application of sensors and their data in assessing SI and the methods to develop these assessments. To understand the current state of research in sensor-based assessment of SI in older adults living in the community and to make recommendations for the field moving forward, we conducted a scoping review. The aims of the scoping review were to 1. Map the types of sensors (and their associated data) that have been used for objective SI assessment, 2. Identify the methodological approaches used to develop the SI assessment, and 3. Synthesize current understandings and knowledge gaps to be addressed in future research. Using an established scoping review methodology, we identified eight relevant articles. Data from motion sensors and actigraph were commonly applied and compared and correlated with self-report measures in developing objective SI assessments. Variability exists in defining SI, feature extraction and the use of sensors and self-report assessments. Inconsistent definitions and use of various self-report scales for measuring SI create barriers to studying the concept and extracting features to build predictive models. Recommendations include establishing a consistent definition of SI for sensor-based assessment research and development and consider capturing its complexity through innovative domain-specific features.
Case Report on Recurrent Dermatofibrosarcoma Protuberans
Authors: Brian Ssenkumba , Mitala Yekosani , Birungi Abraham , Ekuk Eddymond , Kaggwa Sadic 
Published: October 2022

Abstract
Background: Dermatofibrosarcoma protuberans (DFSP) is a potentially malignant soft tissue tumor that if not accurately diagnosed and managed, has a high recurrence rate.
Case presentation: A 35 years old man presented with 5 years history of slowly enlarging, initially painless anterior abdominal wall mass. He had a similar mass at the same location 10 years ago that was excised and diagnosed as a benign fibrous neoplasm. CT scan revealed a soft tissue density well-circumscribed mass that blended with the surrounding soft tissues. Excision was done and histology revealed dermatofibrosarcoma protuberans with atrophy of the overlying skin, positive margins, and areas of fibrosarcomatous change. The tumor was positive for Vimentin and negative for erythroblastosis transcription variant related gene (ERG) and S100. A repeat excision was advised until clear margins were achieved.
Conclusion: Tumor size and herringbone growth pattern do not necessarily imply fibrosarcomatous transformation. Also, accurate diagnosis is key in preventing the recurrence of DFSP. Pathologists need to be aware of such rare cancers since they can easily be missed.
Understanding consumer preferences for integration between mobility-as-a-service (MaaS) and tourism transport in China
Authors: LI Wanying , Guan Hongzhi , Han Yan , Wang Hongfei , Liang Weiwei 
Published: October 2022

Abstract
Mobility-as-a-Service can be customized in various forms depending on the regional and activity travel contexts. Unlike the previous studies dealing with the daily trip and general characteristics of MaaS, this study focuses on more specific contexts like MaaS in tourism transport. An online survey and stated preference experiments were conducted for the first time in China to evaluate consumer preference for different MaaS packages bundled with tourism service, and six discrete choice models were constructed which reflects the interaction of propensity to consume with other attributes. Survey results indicate that MaaS in tourism will find a promising market in China, and more than 50 percent of respondents would choose to use MaaS packages. MaaS consumers can be divided into three categories based on average propensity to consume that conservative consumer group has the highest proportion of the sample, followed by moderate consumer group and aggressive consumer group. Model estimations illustrate those factors affecting whether to subscribe to the MaaS package mainly include MaaS app-related attributes, social environment, and the living location of the respondents; individual socio-demographics, tour preference, and daily travel habits have influences on their choice behaviors of MaaS service pattern. It also reveals that the interaction items of propensity to consume and package-related attributes (i.e., subscription price, period of validity, and tourism preferential price) play significant and heterogeneous roles to consumer interests and preferences for MaaS in tourism.