bluuebunny/crossref_metadata_2025 huggingface dataset:
Change Detection in a Rural Landscape: A case study of processes and main driving factors along with its response to thermal environment in Farim, Iran
Authors: Estalkhsari Bonin Mahdavi , Mohammad Pir , Razavi Niloofar
Published: October 2022

This study aims to investigate the alteration of land use land cover (LULC) change and its response to change in land surface temperature (LST) and heat island phenomena of a rural district of Farim in the north of Iran from 1990 to 2020 using multi-date Landsat data. The LULC result suggests that most land cover type changes are dedicated to bare land with a 24.83 km2 gain (+80.87%). The result demonstrates that the main changing factors of the bare land are population/precipitation and temperature/population. Additionally, the effect of LULC change on seasonal LST and urban heat island (UHI) is also analyzed in this study. The result witnessed a significant rise of LST in both the summer and winter seasons of about 12.87 °C and 14.2 °C, respectively. The urban thermal field variance index (UTFVI) shows the strongest zone in the central area and no UTFVI zone in the surrounding region.
Unsupervised Restoration of a Complex Learned Behavior After Large-Scale Neuronal Perturbation
Authors: Lois Carlos , Wang Bo , Torok Zsofia , duffy alison , bell david , wongso shelyn , velho tarciso , Fairhall Adrienne
Published: October 2022

Reliable execution of behaviors requires that brain circuits correct for variations in neuronal dynamics. Genetic perturbation of the majority of excitatory neurons in a brain region involved in song production in adult songbirds with stereotypical songs triggered severe degradation of their songs. The song fully recovered within two weeks, and substantial improvement occurred even when animals were prevented from singing during the recovery period, indicating that offline mechanisms enable recovery in an unsupervised manner. Song restoration was accompanied by increased excitatory synaptic inputs to unmanipulated neurons in the same region. A model inspired by the behavioral and electrophysiological findings suggests that a combination of unsupervised single-cell and population-level homeostatic plasticity rules can support the observed functional restoration after large-scale disruption of networks implementing sequential dynamics. In the model the sequence is restored through a parallel homeostatic process, rather than regrown serially, and predicts that sequences should recover in a saltatory fashion. Correspondingly, we observed such recovery in the songs of manipulated animals, with syllables that rapidly alternate between abnormal and normal durations from rendition to rendition until eventually they permanently settled into their original length. These observations indicate the existence of cellular and systems-level restorative mechanisms that ensure behavioral resilience.
Optimization of the Culture of Chlorella Sorokiniana PA.91 by RSM: Effect of temperature, light intensity, and MgAC-NPs
Authors: Bisheh masoumeh panbehkar , Amini-rad hasan
Published: October 2022

The condition of the cultivation of newly isolated strains, Chlorella Sorokiniana PA.91, was optimized for the first time for magnesium Amino clay nanoparticles (MgAC-NPs) at various temperatures and light intensities in the culture medium of municipal wastewater (MWW) by Central Composite Design in the Response Surface Methodology (RSM-CCD). This study studied MgAC-NPs synthesized with their characteristics FE-SEM, EDX, XRD, and FT-IR. The synthesized MgAC-NPs were naturally stable, cubic-shaped, within the size range of 30–60 nm. The optimization results show that at culture conditions of 20°C, 37 µmol m− 2s− 1 and 0.05 g L− 1 microalga MgAC-NPs have the best growth productivity and biomass performance. Maximum dry biomass weight (55.41%), specific growth rate (30.26%), chlorophyll (81.26%), and carotenoids (35.71%) were achieved under the optimized condition. Experimental results displayed that C. S PA.91 has a high capacity for lipid extraction (1.36 g L− 1) and significant lipid efficiency (45.1%). Also, in 0.2 g L− 1 of the MgAC- NPs, COD removal efficiency (91.1%) from C.S PA.91 -MgAC-NPs showed. These results showed the potential of C.S PA.91 -MgAC-NPs for nutrient removal in wastewater treatment plants and their quality as sources of biodiesel.
Ionized carbon tracing the assembly of interstellar clouds
Authors: Schneider Nicola , Bonne Lars , Bontemps Sylvain , Kabanovic Slawa , Simon Robert , Ossenkopf-Okada Volker , Buchbender Christof , Stutzki Jürgen , Mertens Marc , Ricken Oliver , Csengeri Timea , Tielens Alexander
Published: October 2022

Molecular hydrogen clouds are a key component of the interstellar medium because they are the birthplaces for stars.
However, the details of how molecular clouds assemble and interact are still largely unknown. Thanks to new observations of the 158 micron line of ionized carbon [CII] in the Cygnus region within the FEEDBACK program on SOFIA, we present for the first time compelling evidence that [CII] unveils dynamic interactions between cloud ensembles. This process is neither a head-on collision of fully molecular clouds nor a gentle merging of only atomic clouds. Moreover, we demonstrate that the dense molecular clouds associated with the DR21 and W75N star-forming regions and a cloud at higher velocity are embedded in atomic gas and all components interact over a large range of velocities (~20 km/s). The atomic gas has a density of ~100 cm-3 and a
temperature of ~100 K. We promote that this type of interaction, solely traced in [CII], is the most common process of molecular cloud formation and anticipate further detections of this phenomenon in other regions.
Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer’s disease
Authors: Yoon Ki-Jun , Kim Mi-Yeon , Kim Mi Jeong , Lee Changyeob , Kim Hyoung Tae , Seo Jinsoo , Han Sungho
Published: October 2022

Enhancing adult neurogenesis in the brain has been suggested as a potential therapeutic for AD. We developed a screening platform ATRIVIEW® for molecules activating neuronal differentiation of adult mouse NSCs. Among FDA-approved drugs, the most potent hit was SNR1611 (trametinib), a selective MEK1/2 inhibitor. We found that trametinib increases the level of P15INK4b and Neurog2, suggesting a mechanism for how MEK1/2 inhibition induces neuronal differentiation. Oral administration of trametinib increased adult neurogenesis in the dentate gyrus and subventricular zone of the AD model mouse 5XFAD. Surprisingly, we also found that trametinib enhanced adult neurogenesis in the brain cortex. Consequently, trametinib rescued AD pathologies such as neuronal loss or cognitive impairment of 5XFAD mice. Finally, trametinib induced neurogenic differentiation of NSCs derived from AD patient iPSCs, which suggests its potential therapeutic application. Altogether, we suggest that restoration of endogenous adult neurogenesis by trametinib may be a promising therapeutic approach to AD.
The Influence of Shielding Gases on Keyhole-Induced Porosity and Nitrogen Absorption in SS 304 Stainless Steel Fiber Laser Welds
Authors: Hafez Khalid Mohamed
Published: October 2022

As regards porosity formation and gas content, choosing the appropriate shielding gas for laser welding is essential for achieving high-quality joints. Keyhole-induced porosity formation tendency and, nitrogen content in fiber laser SS 304 stainless steel welds were investigated based on shielding gas nitrogen contents in fiber laser welding. Beads-on-plate autogenous welds were made at 5 kW continuous wave (CW) fiber laser in N2 and Ar mixtures. Optical metallography, Micro-focused X-ray, X­ray radiography, and High-speed images of the molten pool were used to investigate the porosity formation. In addition, a gas analyzer was used to study the weld metal nitrogen content. The results show that nitrogen has a significant impact on the reduction of porosity in the melting zone, increases the dissolved nitrogen in the solidified weld metal, while almost no significant effect on the keyhole mode.
Extracellular Matrix Viscoelasticity Drives Liver Cancer Progression in Pre-Cirrhotic NASH
Authors: Török Natalie , Fan Weiguo , Adebowale Kolade , Li Yuan , Rabbi Md Foysal , Vancza Lorand , Chen Dongning , Kunimoto Koshi , Mozes Gergely , Li Yisi , Tao Junyan , Monga Satdarshan , Charville Gregory , Wells Rebecca , Dhanasekaran Renu , Kim Taeyoon , Chaudhuri Ovijit
Published: October 2022

Type 2 diabetes mellitus (T2DM) is a major risk factor for hepatocellular carcinoma (HCC). Changes in extracellular matrix (ECM) mechanics contribute to cancer development, and increased stiffness is known to promote HCC progression in cirrhotic conditions. T2DM is characterized by an accumulation of advanced glycation end products (AGEs) in the ECM; however, how this affects HCC in non-cirrhotic conditions is unclear. Here, we find that in patients and animal models AGEs promote changes in collagen architecture and enhance ECM viscoelasticity, with greater viscous dissipation and faster stress relaxation, but not changes in stiffness. High AGEs and viscoelasticity combined with oncogenic β-catenin signaling promote HCC induction, while inhibiting AGEs production, reconstituting the clearance receptor AGER1, or breaking AGE-mediated collagen crosslinks reduce viscoelasticity and HCC growth. Matrix analysis and computational modeling demonstrate that lower interconnectivity of AGEs-bundled collagen matrix, marked by shorter fiber length and greater heterogeneity, enhances viscoelasticity. Mechanistically, animal studies and 3D cell cultures show that enhanced viscoelasticity promotes HCC cell proliferation and invasion through integrin β1–Tensin 1–YAP mechanotransduction pathway. These results reveal for the first time that AGEs-mediated structural changes enhance ECM viscoelasticity, and that viscoelasticity can drive cancer progression in vivo, independent of stiffness.
The role of surgery in relieving calcified shunt site related pain in patients with functioning VP shunt
Authors: Baig Rehman Ali , Davis James , Rodrigues Desiderio , Lo William , Kaliaperumal Chandrasekaran , Gallo Pasquale
Published: October 2022

Purpose

Shunt calcification is a known late sequela of ventriculoperitoneal (VP) shunt insertion and is associated with shunt malfunction. However, in some patients, while shunt functionality is preserved despite calcification of the catheters, they experience nociceptive symptoms. In this paper, the authors present their surgical experience in managing patients with a functional VP shunt and experiencing pain secondary to shunt calcification.

Methods

We analysed outcomes of patients presenting with pain at the level of a calcified shunt who underwent surgical untethering of the calcified catheter from the soft tissues. This procedure was commenced by the senior author in 2015. Patients were collected prospectively from the databases of two institutions. Evidence of shunt calcification was confirmed on neuroimaging.

Results

Seven patients, two male and five female were included. The mean age at untethering was 13.5 years. The mean time interval between primary shunt surgery and symptoms onset was twelve years (range 6–16 years). The commonest site of tethering was the neck (50%) followed by abdomen and chest (both 25%). Six patients underwent untethering of the catheter from soft tissues. One patient had removal of a redundant segment of calcified shunt left in situ during a previous revision. All patients experienced pain relief following shunt untethering.

Conclusion

Untethering of calcified VP shunt catheters from soft tissue can be considered an effective treatment of shunt site pain and offered to patients presenting with a functional VP shunt.
D2d Self-Organization in IOT Via Triple Modular Redundancy Based MDS Code
Authors: Ramamoorthi S , B Muthu Kumar.
Published: October 2022

Device-to-Device (D2D) communication is a key enabling technology to replace base station-to-device(B2D) communication. D2D with IoT realization has spectral and energy-efficient features for on-time quality data transfer. However, the rapid growth of such networks and the dynamic quality of service demands of user equipment require robust and efficient service quality in disasters, outages, and adversarial conditions. To address this challenge, this paper proposes a triple modular redundancy based on the maximum distance separable (TMR-MDS) technique has been proposed, which modifies the repair bandwidth by utilizing more storage occupation and improving the D2D link availability in the system. The proposed TMR-MDS technique will be used, which is composed of two phases: trust management modules and triple modular redundancy storage modules. As part of the initial stage of trust management, a fuzzy logic model is employed to determine the user's trust value after the user's behavior is examined. Second, using the majority voting scheme to improve triple modular redundancy storage. Furthermore, if any problem occurs in the node, then it will self-organize. MATLAB is used to evaluate the performance of the proposed system. The overall system performance is evaluated in terms of the network’s trust level, and the communication cost of the proposed strategy. As per the experimental results, the proposed TMR-MDS method has a better performance of 12.67%, 23.68%, and 25.87% than HBP [4], DR-MDS [5], and URL-RFC [6].
Antifungal activities of vineyard-habitat wild yeast for grape gray-mold disease and its initial promotion of alcohol fermentation in spontaneous winemaking
Authors: Hudagula Hu , Maeno Naoko , Minami Noriko , Takahashi Soichiro , Yoshida Kuniko , Ohtani Katsuki , Funatsu Yasuhiro , Kondo Ryosuke , Yamaguchi Akihiro
Published: October 2022

Microorganisms, including native yeasts, are abundant in vineyard fields. Herein, we studied the possibility of using vineyard-derived wild yeast as a microbial pesticide against Botrytis cinerea, a pathogen that causes grape gray mold disease, to boost the initial alcohol production of spontaneously fermented wine. We identified the Saccharomyces cerevisiae strain KONDO170908, which showed the most effective antifungal activity in an ex vivo yeast dripping experiment on grape berries. This strain was utilized in an in vivo spray test on grape bunches in vineyard fields and was proven to significantly suppress gray mold disease on the grape berries in test plot #16 when the yeast was sprayed during both the flowering and ripening periods (morbidity 11.2% against 15.3% of the control plot, χ2 test, P < 0.0001). However, in test plot #17, spraying the yeast during only the ripening period had no effect (morbidity 16.3%). The grapes from each test plot were also submitted for spontaneous wine fermentation. Alcoholic fermentation of the grapes from test plot #16 provided the most active bubbling of CO2 gas and the highest ethanol production and colony counts over seven days of fermentation. Unique changes in the different strains of S. cerevisiae among the plots were observed throughout the early fermentation stage. Thus, yeast spraying during the flowering period might trigger modification of the entire microbiota and could ultimately contribute to promoting alcohol production in the spontaneously fermented wine.
An Algorithm for Real-Time Sub-Nanosecond Level Time Synchronization Based on RTK Timing Inverse Correction and Kalman Filtering
Authors: Fang Yunlong
Published: October 2022

This article proposes a new algorithm for real-time sub-nanosecond level time synchronization based on GNSS RTK technique and the Kalman Filtering. It is able to improve the performance of time synchronization system as well as a sub-nanosecond level, with a real time response. Although the IGS products theoretically improve the accuracy up to a sub-nanosecond or even higher level, the weakness of more pool performance in a shorter duration and of a lower update rate make us scarcely possibly get an accurate timekeeping upper than nanosecond level only relying on the IGS products. The RTK TIC algorithm uses the RTK position results of (xrtk, yrtk, zrtk) to inversely and iteratively update the time keeping results from pseudorange PVT equations to a high level accuracy. Meanwhile, in order to suppress the error coming from ephemeris change, the FS725 Stanford Rubidium Atomic Clock are used as a compensation equipment for coupling the GNSS timekeeping results via the Kalman Filtering. Then, this paper gives the validation of the RTK TIC algorithm with a two-channel system and compares mean values and standard deviations between our system and two SYN4505As, the results shows our system has a better timekeeping accuracy than the SYN4505As. At last, this paper calibratesthe accuracy of our system via the standard clock source in the NTCS, and gives the results that our system has an excellent performance on the real-time sub-nanosecond level time synchronization.
Predictive value of noninvasive peripheral atherosclerosis measurement for coronary artery disease in patients with long T2DM duration
Authors: Chen Wanjiao , Wang Li , Hu Bin , Zheng Ying , Zhang Shuya , Zhou Zhong , Mai Yifeng
Published: October 2022

Background
Vascular ultrasound is a commonly used tool to predict the existence and severity of coronary artery disease (CAD) by detecting the atherosclerosis of peripheral arteries. However, most studies on atherosclerosis are based on the general population, and the predictive efficacy of carotid or femoral ultrasound in type 2 Diabetes mellitus (T2DM) and its correlation with CAD severity are less elucidated. This study aimed to compare the predictive value of carotid or femoral artery ultrasound for CAD in T2DM patients free from known CAD, and to assess the relationship with the severity of coronary artery stenosis.
Methods
Cross-sectional study in adults with a T2DM duration of at least 5 years and without established CAD. All participants underwent carotid and femoral ultrasound and underwent coronary angiography for the first time. The carotid plaque score (CPS) was calculated by the sum of the maximum thickness of plaques on three segments of the carotid arteries on both sides. The Gensini score was used to assess the severity of coronary stenosis, and patients were divided into no or mild group, moderate group and severe group according to the tertile of the score.
Results
Multiple regression analysis showed that carotid plaque score, femoral plaque and smoking were independently and positively correlated with CAD. Carotid plaque score yielded the highest area under the curve for detecting significant coronary disease (AUC = 0.7323). In contrast, the area under the curve of femoral artery plaque and carotid intima-media thickness was lower than 0.7, which was at a lower prediction level. In the no or mild, moderate and severe groups, the CPS value gradually increased, and the difference between the groups was statistically significant (p < 0.05). The positive rate of femoral artery plaque in patients with moderate and severe CAD was significantly higher than that in the no or mild group (p < 0.0001).
Conclusion
In patients with long T2DM duration, carotid plaque score has a higher ability to predict the occurrence and severity of CAD. However, femoral artery plaque has special value in predicting moderate to severe coronary artery disease in patients with long-term T2DM.
Randomized in situ evaluation of surface polishing protocols on the caries-protective effect of resin Infiltrant
Authors: Esteves-Oliveira Marcella , Passos Vanara Florencio , Russi Tereza M.A.Z.C. , Fernandes Argus R. R. , Terto Caroline N.N. , Mendonça Juliano S. , Campus Guglielmo , Wierichs Richard J. , Meyer-Lückel Hendrik , Lima Juliana P.M.
Published: October 2022

The aim of this placebo-controlled randomized in situ study was to evaluate the effect of different surface polishing protocols on enamel roughness, bacterial adhesion and caries-protective effect of a resin infiltrant. Eighty-four bovine enamel samples having artificial caries lesions were treated with a resinous infiltrant and afterwards randomly dividided into five polishing protocols: aluminum oxide flexible disks (Al2O3-Disks), silicon carbide tips (SIC-Tips), silicon carbide brush (SIC-Brush), silicon carbide polyester strips (SIC-Strips) or no polishing [negative control (NC)]. Average surface roughness (Ra) was assessed by profilometry. Samples were mounted in palatal appliances under a mesh for biofilm accumulation. Fifteen volunteers wore the intraoral appliances (14-days) and cariogenic challenge was triggered by sucrose solutions. Biofilm formed was collected for microbiological analysis of caries-related bacteria (Streptococcus mutans, Lactobacillus acidophilus) and demineralization was assessed by cross-sectional microhardness. Mean Knoop hardness numbers (Kg/mm2) were plotted over lesion depth (µm) and area under the lesion curve was subtracted from sound enamel to determine demineralization (ΔS, Kg/mm2xµm). Data were analyzed by ANOVA and post-hoc comparisons (α=0.05). NC resulted in significantly higher Ra means than Al2O3-Disks and SIC-Strips. Bacterial counts were not significantly different between the groups (p>0.05). Regards ΔS means, however none of the groups were significantly different to NC (6,983.3 Kg/mm2xµm /CI:4,246.1–9,720.5, p>0.05). Conclusions: Polishing protocols (Al2O3-Disks, SIC-Strips) significantly decreseased roughness of infiltrated-enamel, however none of the polishing protocols could signicantly decrease bacterial counts nor resulted in significant less demineralization.
Surgical treatment versus non-surgical treatment for Carpal Tunnel Syndrome: A Systematic Review
Authors: Cao Manting , Hu Hantong , Chen Jing
Published: October 2022

Study design: Systematic review.
Introduction: Carpal tunnel syndrome (CTS) is a common and painful compressive peripheral neuropathy with complex symptoms, caused by pressure on the median nerve as it travels through the carpal tunnel.
Purpose of the Study: This review aimed to develop a critical systematic review of the research evidence to evaluate the effectiveness of non-surgical intervention compared to surgical intervention in the treatment of patients with CTS.
Methods: Four electronic databases (PEDro, PubMed/MEDLINE, Cochrane Library, and Web of Science) and two grey literature databases (US ClinicalTrials. gov, and OpenGrey) were used to perform a comprehensive search of the relevant data.
Results: A total of 686 potentially related studies were found in the four databases, and no relevant studies were found in the two gray literature databases. 10 studies finally met the inclusion criteria and were included in this review.Five studies compared the effect of local steroid injection and surgical treatment on patients with CTS. Two studies compared manual therapy with surgical treatment.; One study compared splinting with surgical treatments; One study make a comparison between a combined non-surgical treatment program and non-surgical treatment; One study compared the effectiveness of splinting, splinting combined with local steroid injection and surgical treatment.
Conclusion:In conclusion, critical analysis of the findings shows that both surgical treatment and non-surgical treatment are effective for the management of patients with CTS. Indeed, surgical treatment shows better effectiveness.
Critical analysis of the findings showed that both surgical and non-surgical treatments are effective for the management of patients with CTS. Thus, surgical treatment is more effective.
Clinical significance of mutational variants in beta and alpha genes in patients with hemoglobinopathies from two large greek centres: a complex interplay between genotype and phenotype
Authors: Diamantidis Michael D. , Karanikola Rebecca-Anastasia , Polyzoudi Chrysoula , Delicou Sophia , Manafas Achilles , Savera Helen , Xydaki Aikaterini , Kotsiafti Angeliki , Tsangalas Evangelos , Ikonomou Georgia , Mani Eirini , Ntoulas Konstantinos , Alexiou Evangelos , Koskinas John , Fotiou Paraskevi
Published: October 2022

Hemoglobinopathies affect patients in the wider Mediterranean area and consist of 4 distinct subgroups: beta thalassemia major (TM), beta thalassemia intermedia (TI), sickle cell disease syndromes (SCD) (homozygous SCD, SCD/beta thalassemia trait) and hemoglobinopathy H (alpha thalassemia). The clinical spectrum of these syndromes varies from mild to severe. Complex interactions between genes and environmental factors form the clinical manifestations in hemoglobinopathies. There is an unmet need to clarify these multifactorial mechanisms. This is the first Greek study, describing mutational alleles (variants in the HBB and HBA1/HBA2 genes, type of mutation and prevalence) in 217 patients with hemoglobinopathies of two large centers in Greece (Larissa and Athens) and associating particular genotypes or gene variants with clinical manifestations (transfusion frequency, complications). Thus, the complex interplay between corresponding genotypes and phenotypes was investigated. The present study results are in accordance with previous national studies with limited variations, due to regional prevalence of specific gene variants, as expected. The type and prevalence of variants in beta and alpha globin genes differ significantly among countries. In the beta thalassemic or SCD patients of our cohort, co-inheritance of variants in the alpha globin genes, leading to absence or reduction of alpha globin synthesis were associated with milder clinical course, whereas the inheritance of additional alpha genes (triplication) led to a more severe clinical phenotype. In cases in whom the genotype and phenotype did not correlate, other factors such as the function or modification of possible regulatory genes or additional nutritional or environmental effects should be investigated.
Does joint-sparing tumor resection jeopardize oncologic and functional outcomes in non-metastatic high-grade osteosarcoma around the knee?
Authors: Huang Mengquan , Ma Ziyang , Yu Jie , Lu Yajie , Chen Guojing , Fan Jian , Li Minghui , Ji Chuanlei , Xiao Xin , Li Jing
Published: October 2022

Background:We previously reported joint-sparing tumor resection for osteosarcoma with epiphyseal involvement in which transepiphyseal osteotomy went through the in situ ablated epiphysis. However, we do not know whether this is a safe approach when compared with joint-sacrificed tumor resection. Our objective was to compare oncologic and functional outcomes between patients who underwent joint preservation (JP) and joint replacement (JR) tumor resection. Furthermore, we identified the risk factors of local recurrence, metastasis and survival.
Methods: Eighty-nine patients with non-metastatic high-grade osteosarcoma around the knee were treated with limb-salvage surgery (JP in 47 and JR in 42). Age, gender, tumor location, pathologic fracture, plain radiographic pattern, limb diameter change, perivascular space alteration, surgical margin, local recurrence, metastasis, death and the Musculoskeletal Tumor Society (MSTS)-93 scores were extracted from the records. Univariate analysis was performed to compare oncologic and functional outcomes. Binary logistic and cox regression models were used to identify predicted factors for local recurrence, metastasis, and survival.
Results:Local recurrence, metastasis and overall survival were similar in the JP and JR group (p =0.3; p=0.211; p=0.143). Major complications and limb survival were also similar in the JR and JP group (p=0.14; p=0.181). The MSTS score of 27.06 ±1.77 in the JP group was higher than that of 25.88±1.79 in the JR group (p=0.005). The marginal margin of soft tissue compared with a wide margin was the only independent predictor of local recurrence (p=0.006). Limb diameter increase and perivascular fat plane disappearance during neoadjuvant chemotherapy were independent predictors for metastasis (p=0.002; p=0.000) and worse survival (p=0.000; p=0.001).
Conclusions: Joint-sparing tumor resection with the ablative bone margin offers advantage of native joint preservation with favorable functional outcomes while not jeopardizing oncologic outcomes compared with joint-sacrificed tumor resection. Surgeon should strive to obtain adequate soft tissue surgical margin decreasing risk of local recurrence. Novel drug regimens might be reasonable options for patients with obvious limb diameter increase and perivascular fat disappearance during chemotherapy.
Genome-wide analysis of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: Complementing in vitro and human data from the INMA cohort.
Authors: D’Cruz Shereen Cynthia , Hao Chunxiang , Labussiere Martin , Mustieles Vicente , Freire Carmen , Legoff Louis , Magnaghi-Jaulin Laura , Olivas-Martinez Alicia , Rodriguez-Carrillo Andrea , Jaulin Christian , David Arthur , Fernández Mariana F. , Smagulova Fatima
Published: October 2022

Objective: To assess the genetic and epigenetic effects promoted by Bisphenol A(BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, as well as in human cells.
Methods: DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). All experiments were performed with material extracted from whole blood of adolescents from INMA. The epidemiological study was complemented by in vitro assessments of human (HeLa) cells exposed to BPA, specifically, immunofluorescence evaluation of histone modification levels, gene expression analysis and ChIP‒qPCR analysis.
Results: Adolescents in the high urinary BPA group presented higher genetic instability of Satellite A (SATA) repetitive region compared to those in the low BPA group. We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2; at LINE1 retroelements; and at the ARID2, EGFR1 and ESRRA genes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. These results were supported by studying HeLa cells exposed to 10 nMBPA in vitro. Exposure of cells to BPA caused a global increase in histone H4 acetylation and a decrease in H3K9me3 levels. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2) were observed, and the expression of several genesencoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) increased. Moreover, increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding at the RARA promoter were observed.
Conclusion: Genome-wide analysis of histone trimethylation and BPA exposure in the in adolescents from the INMA cohort revealed a global impact of BPA on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors, which showed parallels with HeLa cells exposed to a human-relevant dose.
FORWARDS-1; An adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment; a pharmacokinetic-pharmacodynamic study.
Authors: Paterson Louise M , Barker Dominic , Cro Suzie , Mozgunov Pavel , Phillips Rachel , Smith Claire , Nahar Limon K , Paterson Susan , Lingford-Hughes Anne R
Published: October 2022

Background

Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid dependent individuals receiving methadone.

Methods

Opiate dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or Type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60 or 90mg) based on the incidence of ‘dose-limiting toxicity’ (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 hour later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone) and adverse events will be obtained using validated questionnaires and examinations periodically for 5 hours after dosing.

Discussion

Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30mg of baclofen in patients receiving ≤ 60mg/d methadone based on clinical experience of baclofen’s use in alcoholism and guidelines for the management of opiate dependence.
Trial registration: Clinicaltrials.gov: NCT05161351, registration date: 16 Dec 2021.
Pre-T cell receptor signaling drives leukemogenesis and is a therapeutic target in T-cell acute lymphoblastic leukemia
Authors: Meter Michael Van , Gao Jie , Wang Wei , Kunz Arthur , Bay Andres Perez , Nittoli Thomas , Thurston Gavin , Kuhnert Frank
Published: October 2022

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive lymphoid neoplasm resulting from the malignant transformation of T-cell progenitors. T-ALL leukemogenesis is strongly influenced by its developmental origins.NOTCH1, a critical regulator of early thymocyte development, is mutated in ~ 60% of T-ALL. Less is known about how other determinants of thymocyte development participate in T-ALL leukemogenesis. Using a thymus transplantation-based model of T-ALL, we found that multiple β-selection checkpoint factors were upregulated in leukemic T cells, including Ptcra, a subunit of the pre-T cell receptor (pre-TCR). Genetic ablation ofPtcradramatically reduced the occurrence of T-ALL in this model. In human T-ALL cell lines, knockout ofPTCRAreduced proliferative capacity and the ability to form tumors in vivo, supporting a driver oncogenic role. T-cell antigen-directed immunotherapies face the potential hurdle of inducing severe immunosuppression due to depletion of normal T cell populations. Analysis of clinical T-ALL samples demonstrated thatPTCRAis highly and specifically expressed in leukemic T cells but not in normal, mature T cells. Finally, we demonstrate that PTCRA-directed antibody-drug conjugates have anti-leukemic activity in vitro and in vivo. Cumulatively, our findings highlight an important role for pre-TCR in driving T-ALL and support further evaluation of PTCRA-directed therapies.
Efficacy of radiofrequency ablation versus ethanol ablation for Morton's neuroma: a clinical trial using patient recorded outcome measures
Authors: Silvester Renee , Nargahi Reza , Woods John , Schoen Deborah
Published: October 2022

Background Morton’s neuroma is a common cause of forefoot pain and can be difficult to treat. Ethanol ablation (ETA) and Radiofrequency ablation (RFA) are increasingly used for treatment of chronic Morton's neuroma. However, there is limited evidence on the effectiveness of these guided ablation therapies in relation to broad-ranging patient recorded outcome measures (PROMs), and prospective studies directly comparing the two interventions are lacking. In this pragmatic clinical trial, we aimed to compare the efficacy of Ethanol ablation (ETA) and Radiofrequency ablation (RFA) on patient recorded outcome measures (PROMs) in pain, function, and ability in patients with Morton's neuroma.
Methods Participants with chronic Morton's neuroma were randomly assigned to either ETA or RFA. Outcome measures were the Visual Analogue Scale (VAS), the eight-domain Foot Health Status Questionnaire (FHSQ) and the Foot and Ankle Ability Measure (FAAM). These were assessed at baseline, three, and six months after treatment.
Results Sixty-three participants were allocated to either RFA (n=35) or ETA (n=28). A slight decrease in pain ascertained through VAS scores was observed in both intervention groups over six months relative to baseline. FAAM scores moderately improved in both groups over six months, with ETA showing a marginally greater mean change compared to RFA (3.8 points; p=0.004). FHSQ scores improved from baseline to six months in both groups, across all domains except vigour, which decreased in both interventions over three months and then stabilised in the ETA group at six months. Between-group differences of minor clinical importance favouring the ETA group were reported in improvement from baseline to six months of foot pain (3.7 points on 100 point scale; p<0.005), foot function (3.3 points; p=0.017), general health (2.5 points; p=0.013), and physical activity (11.0 points; p<0.001).
Conclusion In the treatment of chronic Morton’s neuroma, ETA and RFA appear to confer comparable six-month improvements in pain, foot health, function, and ability. Multi-dimensional scales such as the FHSQ and the FAAM potentially elicit substantial treatment-related improvements that are not evident from VAS. Accordingly, incorporation of diverse PROMs into clinical assessments may enhance therapeutic decision-making and research in this context.
Trial registration Australian New Zealand Trials Registry (ANZCTR) ACTRN12622000912785 (retrospectively registered on 27/06/2022
Naturally Selected CD7 CAR-T Therapy without Genetic editing Exerts Significant Antitumor Efficacy against Relapsed and Refractory Acute Myeloid Leukemia(R/R-AML)
Authors: Lu Yu , liu Ying , Zhang Xuejun , Kuang Na , wen shupeng , Wang Fuxu
Published: October 2022

Background Survival time for patients with relapsed and refractory acute myeloid leukemia (R/R-AML) remains threatened and treatment appears challenging. Chimeric antigen receptor T cell (CAR-T) has been widely used for hematologic malignancies. Current CAR-T therapies for acute myeloid leukemia mostly target myeloid-lineage antigens such as CD123 and CD33, which may have potential hematopoietic toxicity. CD7, as a lineage-specific receptor, is expressed in acute myeloid leukemia cells and T cells, while not expressed in myeloid cells. Methods In this report, Immunohistochemistry and flow cytometry were used to analyze CD7 expression in clinical samples from R/R-AML patients and healthy donors. we designed naturally selected CD7 CAR-T to analyze various functions and in vitro anti-leukemic efficacy by flow cytometry, while xenograft models were used to validate in vivo tumor dynamics Results we calculated the percentage of CD7 expression in our institution's AML patients with minimal residual disease (MRD) (5/16, 31.25%) and tested CD7 in myeloid and lymphoid lineage cells of R/R-AML patients, concluding that CD7 is expressed in T cells and not in myeloid cells, similar to previous studies. Subsequently, we constructed and designed a naturally selected CD7 CAR-T (CD7 CAR). We did not perform CD7 antigen knockdown on CD7 CAR-T cells, but it naturally eliminated CD7 molecule expression at the end of the culture cycle and then evaluated its ability to target and kill the acute myeloid leukemia cell line MOLM-13 in vitro and in vivo. CD7 CAR-T cells efficiently murder acute myeloid leukemia cells in vitro and significantly inhibit the growth of leukemia cells in xenograft model mice. Conclusion Naturally Selected CD7 CAR-T cells were proven to be an effective and safe treatment strategy for relapsed refractory acute myeloid leukemia in preclinical studies.
Original Research Chaihu-Guizhi-Ganjiang Decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis
Authors: Li Mingming , Zhu Jiawei , Liu Xuan , Dong Zhiyin , Tang Jigui , Zhang Cian , Jiao Jianpeng , Chen Jiani , Yin Fenghao , Qiu Shi , Zhang Feng , Gao Shouhong , Wang Zhipeng , Tao Xia , Yue Xiaoqiang , Sun Lianna , Chen Wansheng
Published: October 2022

Background

Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza in China. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment are not known.

Methods

Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. Efficacy and changes in metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis undertaken.

Results

Efficacy was measured by two systems: the Rome IV criteria and TCM theory. Irrespective of whether the Rome IV criteria or TCM theory were used, CGGD showed significantly better efficacy than Dicetel against IBS. CGGD also had a greater influence on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD use led to increased carnitine metabolism, with increased levels of L-carnitine and acylcarnitine. Such changes in these metabolites could suppress IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation.

Conclusions

CGGD appeared to be more efficacious than Dicetel in treating IBS. Metabolomics analysis helped to reveal the biomolecular basis of this beneficial effect.
Clonal outbreak of Trichophyton tonsurans causing tinea capitis among a wrestling team in Beijing, China
Authors: Wang Qiqi , Chen Wei , Wan Zhe , Liu Wei
Published: October 2022

Trichophyton tonsurans, an anthropophilic dermatophyte, mostly causes tinea capitis and tinea corporis and often associates with outbreaks among athletes involving in combat sports. Here, we report an outbreak of tinea capitis caused by T. tonsurans among five juvenile athletes aged ten to fourteen in a wrestling team in Beijing, China. Scrapings from the lesions of the five patients were performed by direct microscopic examination and fungal culture. The fungal pathogens were all identified as T. tonsurans by morphology and sequencing of the internal transcribed spacer (ITS) regions. Multilocus genotyping analysis was performed by sequencing of the five gene loci including the ITS and non-transcribed spacer (NTS) of the ribosomal RNA (rRNA) locus, alkalineprotease-1 (ALP1), metalloprotease-5 (MEP5), carboxypeptidases Y (CarbY). The sequences of these markers were identical among the five isolates, revealing a single genotype. Antifungal susceptibilities of terbinafine (TBF), itraconazole (ITC), fluconazole (FLC), ketoconazole (KTC), and amphotericin B (AMB) against T. tonsurans was determined by broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 document and the minimum inhibitory concentrations (MICs) were 0.015 µg/mL, 0.015 µg/mL, 8 µg/mL, 0.06 µg/mL, and 0.5 µg/mL, respectively. In conclusion, we report an outbreak of tinea capitis caused by T. tonsurans among wrestlers in Beijing, China. Multilocus genotyping analysis revealed that all isolates consisted of a single genotype, suggesting the outbreak may be caused by a single strain of T. tonsurans. The isolates were all susceptible to the common antifungal drugs treating tinea capitis.
EMI shielding and strain-sensitive tape based on ultraprecise 3D printed graphene oxide aerogel microlattices
Authors: Chen Qian , Shen Junting , Estevez Diana , Chen Yanlin , Zhu Zihao , Yin Jun , Qin Faxiang
Published: October 2022

3D printed graphene aerogels hold promise for multifunctional applications due to their elasticity, low density and adjustable conductivity. However, low printing accuracy/fidelity and stochastic porous networks have hindered both research and applications. Here we formulate printable graphene oxide (GO) inks through modulating oxygen functional groups and trace addition of Ca2+ ions as gelators. Self-standing 3D graphene aerogel microlattices (GOALs) were thus printed with minimal shrinkage and ultra-high printing resolution of 70 μm. The improved resolution facilitated customizable 3D structure and inner pore architecture which was exploited for EMI shielding by modulating the lattice aperture and layers in the scaffold. The GOALs were then replicated into adhesive tape as a simple and large-scale strategy to adapt their functionalities into target applications. The GOAL tape is highly durable displaying not only excellent shielding (SSE/t=5714.3 dB cm2/g) but outstanding resistive bending sensitivity (gauge factor=90) making it promising for stealth and flexible sensing electronics.
Non-Rectangular Neurostimulation Waveforms Elicit Varied Sensation Quality and Perceptive Fields on the Hand
Authors: Collu Riccardo , Earley Eric J. , Barbaro Massimo , Ortiz-Catalan Max
Published: October 2022

Electrical stimulation of the nerves is known to elicit distinct sensations perceived in distal parts of the body. The stimulation is typically modulated in current with charge balance rectangular shape that, although they are easily generated by the stimulators available on the market, they are not able to cover the entire range of somatosensory experiences required in daily life. In this regard, we have investigated the effect of electrical neurostimulation with four non-rectangular waveforms in an experiment involving 11 healthy able-bodied subjects. Weiss curves were estimated for different subjects, showing different charges required to elicit a sensation based on the shape. The localization and dimensions of the sensations reported in the hand also differed between waveforms showing larger areas for non-rectangular waveforms. Finally, the possibility of distinguishing different charge- and amplitude-matched stimuli was demonstrated through a two-alternative-forced-choice (2AFC) task, showing the ability of participants to successfully distinguish between waveforms. This study shows that by using different waveforms to stimulate nerves, it is possible to affect not only the required charge to elicit sensations, but also the quality of sensation and its dimension, in terms of area and location.