bluuebunny/crossref_metadata_2025 huggingface dataset:
PMT Signal Transmission for Hard X-Ray Diagnostics of Future Tokamaks
Authors: Nowakowski Patryk Nowak vel , Makowski Dariusz , Walewski Wojciech
Published: April 2022

A pair of a scintillator and a Photomultiplier Tube (PMT) is often used as a Hard X-Ray (HXR) radiation detector in existing tokamaks such as JET, EAST, COMPASS or ASDEX-U. Future nuclear fusion reactors such as ITER or DEMO will use more powerful magnets and confine a larger volume of hot plasma. Placement of the detectors used for plasma diagnostic will be constrained by high temperatures, magnetic fields and ionizing radiation present near the tokamak vessel. It might be necessary to move detectors away from tokamak to a safer location. As a result, it might generate problems with pulse discrimination and transmission of the signal. In such scenario, a new approach to the design of plasma diagnostic systems such as HXR spectroscopy is required. In case of the ITER tokamak, sensitive electronics such as Field-Programmable Gate Arrays (FPGA) cannot be installed close to the reactor. The signal from the PMT will be transmitted via an over 100 m long cable to a digitizer located in the diagnostic building. Along the way, electromagnetic interferences can couple into the cable. Additional measures have to be taken to reduce the influence of noise on the signal. The paper presents issues with signal transmission in HXR diagnostic systems and includes a discussion on the methodology of PMT signal transmission in the conditions of the future tokamaks. A proposal of guidelines for selection of the signal chain components and design of a dedicated PMT amplifier is part of this paper.
Tumor suppression by Chinese cordyceps extract via anti-angiogenesis
Authors: Li Wenjia , Li Jing , Hu Xuefeng , Xu Linghua , Liu Xiaoyu , Qian Zhengming , Jin Liling , Zhang Yimin , Wei Jiangchun , Liu Xingzhong
Published: April 2022

Development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen is a novel strategy for tumor therapy. Chinese cordyceps (Ophiocordyceps sinensis), a traditional Chinese herb, has been widely reported to exhibit antitumor effects. In the present study, we tested suppression of Chinese cordyceps extract (CCE) on tumor angiogenesis in tube formation assay using human umbilical vascular endothelial cells (HUVECs) in vitro and Lewis carcinoma xenografts in mice. In addition, CCE was also investigated in an ex vivo angiogenesis assay using rat aortic rings. CCE could dose-dependently suppress capillary tube formation in HUVECs as well as in rat aortic ring. The antiangiogenesis activity of CCE was further verified in Lewis xenografted mice models where tumor volume was significantly decreased in the treatment of CCE at 100 mg/kg. The mean vascular density (MVD) in the tumor, measured by platelet endothelial cell adhesion molecule-1 (CD31) immune-histochemical staining, was also markedly inhibited by CCE at 100 mg/kg treatment. These results indicated that Chinese cordyceps may have antitumor activity through antiangiogenesis activity and could be used in prevention and/or therapy of angiogenesis related cancers.
Effects of void deck on the airflow and pollutant dispersion in 3D street canyons
Authors: Sin Chung Hyok , Luo Yang , Jon Kwang Song , Cui Peng-Yi , Huang Yuandong
Published: April 2022

In general, urban canyons are the areas most clearly affected by traffic pollutants since the ability of the canyon to self-ventilate is inhibited due to blockage of buildings or other urban structures. However, previous studies have aimed to improve the pedestrian-level wind speed with void deck in single buildings or short canyons. This study investigated the effects of void deck height and location, and building height on the airflow field and the traffic pollutant diffusion in a long canyon with L/H=10, validated by wind-tunnel experiment data. The results show that the void decks have a significant effect on the airflow and pollutant distribution inside the canyon. Air exchange rates (ACH) of the canyons with the void deck are much larger than that of regular canyons, and the perturbation changes of turbulence (ACH') decrease. When the void deck is at both buildings, the ACH is the highest, followed by the case where the void deck is at the leeward building. Also, for the canyons with the void deck, traffic pollutants are removed out of the canyon by the strong airflow through the void deck. Therefore, unlike the regular canyons, as the void deck and the building height increases, the strength of the airflow through the void deck becomes stronger, and as a result, the mean pollutant concentration is significantly reduced at both walls and the pedestrian respiration level. The mean pollutant concentration on the wall of the building with the void deck and on the pedestrian respiration plane close to it is near zero. These findings can help ease traffic pollution inside the street canyons composed of high-rise buildings, especially in tropical cities.
Mitochondrial transfer alters cell fate by remodeling metabolic processes to regulate bone homeostasis
Authors: Zhang Yufeng , Cai Wenjin , Zhang Jinglun , Yu Yiqian , Ni Yueqi , Wei Yan , Cheng Yihong , Han Litian , Xiao Leyi , Ma Xiaoxin , Wei Hongjiang , Ji Yaoting
Published: April 2022

Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, we examined mesenchymal stem cell (MSC) regulation by macrophages in the bone marrow environment. We found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes and metabolic statuses release oxidatively damaged mitochondria. The transfer of dysfunctional mitochondria to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. We showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.
Temperature measurement and transfer control of a supercritical hydrocarbon fluid
Authors: Zhang Lei , Zhang Ruoling , Wang Xiangyi , Jiang Jin
Published: April 2022

The measurement method of the fluid temperature suitable for small channel is given, and a fluid transfer control scheme of the area of injecting holes is designed using the balance equations of fluid mass, energy and entropy. A convective heat transfer experiment is conducted to evaluate the temperature measurement and fluid transfer control methods of the heat absorbing supercritical hydrocarbon fluid. The result shows during the heating process the injecting pressure meets the requirement, and the fluid transfer control system works well. The result can be useful for the design of regenerative cooling for hypersonic propulsion system.
Plant-soil feedbacks buffer plant communities from extinction risks in unpredictable environments
Authors: Caruso Tancredi , Rillig Matthias C
Published: April 2022

Theory and experiments have demonstrated that negative plant-soil feedback promotes coexistence between plant species. Plants and soils, however, face the challenge of an increasingly unpredictable environment due to multiple global change factors, including but not limited to climate change. Environmental stochasticity generally reduces the space for coexistence between competing species and it induces fluctuations that increase the variability and unpredictability of community properties such as total productivity. In this paper, we formulate a stochastic version of a classical plant-soil feedback deterministic model, which describes the outcome of plant species competition in the presence of soil feedback. If the soil feedback is negative, the deterministic expectation is that pulse perturbations to the system (e.g. a drought episode) cause plants and soil to move away from their equilibrium to eventually return to it through periodic and exponentially decaying fluctuations. Environmental stochasticity alters this expectation: the system can either settle into a fluctuation regime around the deterministic expectation, or some components of the system may go extinct. Our model results show that while the probability of extinction predictably increases with environmental stochasticity, the more negative the soil feedback, the more it can counteract the increase in extinction probability caused by increased environmental stochasticity, which can be empirically tested. The impact of plant-soil feedback, however, depends on the type of interactions that link soil to plants. These results suggest that plant communities in which strong negative soil feedbacks operate are better placed to withstand the risk posed by increased environmental stochasticity.
Tobacco smoking in men and women with different perceptions of social well- being: Findings of a large population-based study
Authors: Masihay-Akbar Hasti , Mehrabi Fahimeh , Mardi Neda , Amiri Parisa , Cheraghi Leila , Eini-Zinab Hassan , Azizi Fereidoun
Published: April 2022

Background: This study aimed to investigate cigarette and hookah smoking in a population of Eastern-Mediterranean adults in relation to their perceived social well-being. Methods: Data of 2592 adults who participated in the 6th phase (2014-2016) of the Tehran Lipid and Glucose Study (TLGS) was used. After excluding those with missing data (n=235), 2357 remained for the sex-specific logistic regression to investigate the association between social well-being and current smoking (cigarette and hookah). The final model was adjusted for age, marital status, education, occupation, physical activity, and chronic disease history. Results: Compared to cigarette and hookah smokers, the mean scores of social well-being and all its dimensions were higher in non-smokers. While in men, cigarette smoking was significantly related to social well-being and all its dimensions, only women with higher social well-being, social integration, and coherence, were further at risk of cigarette smoking. Unlike men, whose hookah smoking was not at all related to their social well-being, women's hookah consumption was associated with social well-being, social integration and acceptance; one unit increase in the mean scores of social integration and acceptance in women reduced the risk of hookah use by 8%. Conclusion: Social well-being and tobacco smoking are related, and evident sex differences in this relationship should not be ignored in future tobacco control efforts.
Experimental study on residual stress in high-speed grinding of noncircular equidistant profile
Authors: Liu Wei , Yuan Houcai , Shi Xinyu , Liu Tao , Du Shishuai
Published: April 2022

To explore the formation mechanism of residual stress in the high-speed grinding of noncircular equidistant profile, the orthogonal experiments were designed with three grinding parameters including the grinding wheel speed, workpiece speed and grinding depth. A ceramic bond CBN grinding wheel was used for the high-speed grinding of noncircular equidistant profile by the X-C axis linkage. The effects of the three grinding parameters on the grinding temperature, surface roughness and residual stress were analyzed. The results show that with the increase of grinding wheel speed, the grinding temperature and residual stress increase, and the surface roughness decreases. As the increase of workpiece speed, the grinding temperature and residual stress decrease, and the surface roughness increases. As the increase of grinding depth, the grinding temperature, residual stress and surface roughness increase. Besides, the grinding depth has the greatest influence on the residual stress, followed by the grinding wheel speed and workpiece speed.
Gastroprotective effect of 8-alkylberberine derivatives on ethanol-induced gastric ulcer in rats
Authors: Shang Yuanhong , Tian Jinfeng F.
Published: April 2022

Berberine (BBR) is an isoquinoline alkaloid which protects the acute gastroenteritis and inhibits gastric ulcers, and 8-Alkylberberine (8-BBR-Cn, n=4, 8, 12 and 16) with a long aliphatic chain are synthesized have been reported. This paper investigated the possible mechanisms underlying the gastroprotective effect of 8-BBR-Cn derivatives at dose of 25, 50 and 100 mg/kg body weight on enthanol-induced gastric mucosal injury in rats. The ulcer index and percentage inhibition were evaluated. The stomachs tissues were chosen for determination of nitric oxide synthase (NOS) activity and prostaglandin E2 (PEG2) levels, and assay kit were used for the above two assays. Compared with model control group, the ulcer indexes of 8-BBR-Cn (25, 50 and 100 mg/kg, i.g.) treatment groups decreased significantly. Additionally, 8-BBR-Cn could enhance PEG2 concentration in mucosal tissue of gastric ulcer rats. Moreover, in mucosal tissue, activities of total NOS (TNOS) and constitutive NOS (cNOS) were increased, but inducible NOS (iNOS) was decreased by 8-BBR-Cn. 8-BBR-Cn derivatives had protective effect on gastric mucous membrane, and 8-BBR-C16 displayed stronger gastroprotective effect as carbon chain at C8 position lengthens, which was related to prostaglandin E2 and nitric oxide synthase pathways.
Identification of a Novel Pathogenic LDLR Mutation in a Chinese Family with Familial Hypercholesterolemia
Authors: Zha Ling-Feng , Wang Jing-Lin , Chen Qian-Wen , Dong Jiang-Tao , Xie Tian , Jiao Jiao , Nie Shao-Fang , Tu Xin , Cheng Xiang
Published: April 2022

Background: Familial hypercholesterolemia (FH) as the most common risk factor for premature coronary artery disease (CAD), results in huge economic burden on families and society, but it could be significantly under-diagnosed. Methods: In this study, we identified a pathogenic frame shift insertion mutation in LDLR (c.2517_2518insCA, p.C839fs) from a Chinese FH family through whole exome sequencing (WES) and sanger sequencing, which hasn't been reported before. According to the 2015 ACMG/AMP, the nonsense pathogenic mutation on LDLR (c.2517_2518insCA, p.C839fs) was classified as “pathogenic”. Results: This LOF mutation was estimated to change the free energy dynamic of RNA molecule, thus its stability and protein structure were predicted to eliminate an essential LDLR functional domain. Conclusions: This finding expanded our understanding of Phenotype–Genotype correlations of FH with LDLR gene mutations and emphasized the important role of genetic testing and genetic screening in the diagnosis and intervention of FH.
Rhizobium alarensis sp. nov., and Rhizobium halophilensis sp. nov., isolated from the nodule and rhizosphere of Lotus japonicus
Authors: Wan Chuanxing , Shen Hongling , Luo Xiaoxia , Xia Zhanfeng
Published: April 2022

Two strains (TRM95111T and TRM95001T) of Gram-stain-negative, aerobic, rod-shaped mycrobacteria were isolated from the nodule and rhizosphere of Lotus japonicus grown in the campus of Tarim University in Alar, Xinjiang, China. Strain TRM95111T and strain TRM95001T shared 93.1% 16S rRNA gene sequences similarity with each other and had 98.2% and 97.9% 16S rRNA gene sequence similarity to the closest species Rhizobium subbaraonis JC85T and Rhizobium halotolerans AB21T, respectively. Phylogenetic analyses based on 16S rRNA gene sequences, two housekeeping gene sequences (recA, atpD) and core genes showed that two strains belonged to the genus Rhizobium. The values of digital DNA-DNA hybridization (dDDH) between strain TRM95111T and the closest strains R. subbaraonis JC85T and R. azooxidifex Po 20/26T were 21.8% and 21.4%, respectively. The dDDH values between strain TRM95001T and the closest strains R. halotolerans AB21T and R. flavum YW14T were 22.6% and 26.7%, respectively. Whole genome average nucleotide identity (ANI) values of the strain TRM95111T were 75.6%-77.5% and strain TRM95001T were 79.2%-79.6%, compared to their closely related strains. The G + C content values of strain TRM95111T and TRM95001T were 65.1 mol% and 60.7 mol%, respectively. Two isolates contained predominant quinone of Q-10 and the major fatty acids was C18:1ω7c and they were sensitive to 1 µg of amikacin and kanamycin. The polar lipids of strain TRM95111T included unidentified aminophospho lipids (APL1-3), unidentified phospholipids (PL1-2), phosphatidylcholine (PC), unidentified lipids (L1-5) and phospholipids of phospholipids of unknown structure containing glucosamine (NPG), compared to the polar lipids of strain TRM95001T including unidentified aminophospho lipids (APL1-3), unidentified phospholipids (PL1-2), phosphatidylcholine (PC), unidentified lipids (L2-5), hydroxy phosphatidy ethanolamine (OH-PE) and phospholipids of phospholipids of unknown structure containing glucosamine (NPG). Nodulation tests showed that two strains could induce nodules formation in L. japonicus. Based on genomic, phenotypic and phylogenetic analyses, strain TRM95111T and strain TRM95001T are suggested to represent two new species of the genus Rhizobium, whose names are proposed as Rhizobium alarensis sp. nov. and Rhizobium halophilensis sp. nov. The type strains are TRM95111T (= CCTCC AB 2021116T = JCM34826T) and TRM950011T (= CCTCC AB 2021095T = JCM34967T), respectively.
Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals
Authors: Hong Yun Jeong , Kim Chanmi , Lee Jae Hong , Sepulcre Jorge
Published: April 2022

Background:The correlations between apolipoprotein epsilon 4 (APOE4) status and regional amyloid, tau, and cortical thickness in cognitively normal elderly are not fully understood. Our cross-sectional study aimed to compare regional amyloid/tau burden, and cortical thickness according to APOE4 carrier status and assess correlations between APOE4 and Alzheimer’s disease (AD)-related biomarker burdens.Methods:We analyzed 185 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Participants aged 55–90 with normal cognitive function were divided into amyloid ꞵ-positive (Aß+) APOE4 carriers (group 1, n=27), Aß+ APOE4 non-carriers (group 2, n=29), and Aß- normal controls (group 0, n=129). We compared amyloid depositions, tau depositions, and cortical thickness among the 3 groups and assessed correlations between APOE4 existence and imaging biomarkers adjusted for age and sex. Results:The participants in group 2 were older than those in the other groups. The regional amyloid/tau standardized uptake value ratios (SUVRs) did not differ between groups 1 and 2, but the amyloid/tau SUVRs in most regions were numerically higher (especially in the younger (<70) participants) in group 1 than group 2 after adjusting for age difference. APOE4 allele had robust correlations with increased amyloid burden in the fronto-temporo-parietal cortical areas after adjustment for age and sex, but it had weaker and mixed correlations with the regional tau burden and did not have significant correlation with cortical thickness.Conclusions:We identified that the presence of APOE4 allele might be more highly associated with amyloid deposition than with other AD-related biomarkers such as tau or cortical thickness, especially in the younger group below 70 in cognitively normal elderly.
Peripheral CD8+CD28- T cell level reflects tumor immunity and could predict anti- HER2 based therapy response in metastatic breast cancer
Authors: Li Hui-Ping , Liu Xiao-Ran , Cheng Xiang-Ming , Xie Feng , Li Kun , Shi Yong-Can , Shao Bin , Liang Xu , Wan Feng-Ling , Liu Yi-Qiang
Published: April 2022

Purpose: Despite recent clinical improvements, HER2-positive metastatic breast cancer (MBC) is still incurable. A robust biomarker is needed in predicting the efficacy of anti-HER2 based therapy. Experimental Design: A total of 252 HER-positive MBC patients received first-line therapy were retrospectively recruited at two medical centers. Peripheral lymphocyte levels of baseline and subsequent follow-up visits were detected using flow-cytometer. The cutoff value of peripheral CD8+CD28-T cell (pTCD8+CD28-) was determined by X-tile software. The levels of TILs, immune cytokines and mutation prevalence were compared between pTCD8+CD28-high (≥18.0%) and pTCD8+CD28-low. Results: The median follow-up time was 29.6 months. pTCD8+CD28-high at baseline indicates a better PFS in patients received anti-HER2 based therapy (11.1 vs. 18.9 months, P = 0.001). During the therapeutic course, patients who maintained or regain pTCD8+CD28-high had a better PFS than those maintained pTCD8+CD28-low (15.5 vs. 11.1 vs. 7.7 months, P < 0.001). The higher IL-2 level (P = 0.034) and lower TGF-β level (P = 0.016) in the serum were connected to pTCD8+CD28-high. Highly infiltrated TILs including CD8 + CD28-T cell and higher prevalence of PD-L1 deletion (P = 0.041) were associated with pTCD8+CD28-high. The elevated pTCD8+CD28-level induced by anti-PD1 therapy was also observed in triple-negative MBC patients.Conclusions: The pTCD8+CD28-level at baseline and its dynamic change are predictive for anti-HER2 based therapy. Higher pTCD8+CD28-level is associated with an enhanced tumor immunity in HER2-positive MBC. Adding anti-PD1 therapy to HER2-targeted therapy according to pTCD8+CD28-level could be a promising alternative.
Optimization of Furrow Irrigation Decision Variables: The case of Wonji Shoa Sugarcane Plantation, Ethiopia
Authors: Adamu Tokuma , Ayana Mekonen , Aregay Gebremeskel
Published: April 2022

Surface irrigation type is one of the most widely used in the world due to its low cost investment. However it is complex method of applying water to soil, because of extreme difficult to achieve good control over the highly variable nature of the movement of water across a soil surface and its infiltration into the soil over a season. This study is attempted to optimize furrow irrigation decision variables at Wonji sugar estate using field experiment and two simulation models. The field data of experimental site was measured as input for models and simulated using the SIRMOD software and WinSRFR software package. Furrow lengths of 32m, 48m and 64m, slopes of 0.05%, 0.075% and 0.1%and flow rates of 3l/sec, 4l/sec and 5l/sec were analyzed with three replication using volume balance method and two simulation models. The study found optimum decision variables that gave maximum application efficiency and distribution uniformity were slope of 0.1%, furrow length of 32m and inflow rate of 4 l/sec at cut-off time of 15.79 minutes. Thus, to improve the performance of furrow irrigation practice, optimal furrow length, inflow rates and cut-off time found by this study should be adopted. Findings from the study would serve as a source of information for use by policy makers and planners during the design and Operation of irrigation development programs. It does not focus on yield related optimization. So, it is open for the future research to conduct yield related optimization of the decision variables. The authors sincerely declare that this study is the product of their own efforts.
Radiographic analysis of dynamic lumbar motion during the five-repetition sit-to-stand test in degenerative lumbar spondylolisthesis
Authors: jiang Jiang , Hu Jun , Cai Hai-ping , Niu Lei , Zheng Meng-long , Chen Xi , Zhang Wen‑zhi
Published: April 2022

Background
To investigate the mechanisms of low back pain (LBP) triggered by the five-repetition sit-to-stand test (5R-STS test) in degenerative lumbar spondylolisthesis (DLS) from radiographic perspective, as well as to determine the most useful diagnostic modalities in the evaluation of segmental instability.
Methods
We retrospectively performed a study of 78 patients (23 men and 55 women) with symptomatic DLS at L4/5 in our institution between April 2020 and December 2021. Each patient was assessed by using the 5R-STS test and received a series of radiographs including the upright standing, natural sitting, standing flexion-extension radiographs, and supine sagittal MRI. Enrolled patients were divided into two groups based on the 5R-STS test score: severe group and mild group. Translational and angular motion was determined by comparing nature sitting radiograph (S) with upright standing radiograph (N) (Combined, SN), flexion/extension radiographs (FE) as well as nature sitting radiograph (S) with a supine sagittal MRI image (U) (Combined, SU).
Results
Overall, 78 patients were enrolled, and there were 31(39.7%) patients in group S and 47(60.3%) patients in group M, with an average age of 60.7 ± 8.4 years. The natural sitting radiograph demonstrated the maximum slip percentage (SP) and the highest kyphotic angle both in group S and group M. Compared with group M, group S revealed significantly higher SP in the natural sitting position (24.1 vs 19.6; p = 0.002). The lumbar slip angular in group S with a sitting position was significantly higher than that in group M (-5.2 vs -1.3; p < 0.001). All patients in group S had OFI and 28 patients of them were diagnosed with lumbar instability by using the combination of nature sitting radiograph (S) and supine sagittal MRI image (U) (Combined, SU).
Conclusion
DLS patients with positive sign of the 5R-STS test is a distinct subgroup associated with lumbar instability. The modality of the combination of nature sitting radiograph (S) and supine MRI (U) had a significant advantage in terms of the ability to identify segmental instability.
Existence of Weakly Quasisymmetric Magnetic Fields in Asymmetric Toroidal Domains with Non-Tangential Quasisymmetry
Authors: Sato Naoki
Published: April 2022

A quasisymmetry is a special symmetry that enhances the ability of a magnetic field to trap charged particles. Quasisymmetric magnetic fields may allow the realization of next generation fusion reactors (stellarators) with superior performance when compared with classical (tokamak) designs. Nevertheless, the existence of such magnetic configurations lacks mathematical proof due to the complexity of the governing equations. Here, we prove the existence of weakly quasisymmetric magnetic fields by constructing explicit examples. This result is achieved by a tailored parametrization of both magnetic field and hosting toroidal domain, which are optimized to fulfill quasisymmetry. The obtained solutions hold in a toroidal volume, are smooth, possess nested flux surfaces, are not invariant under continuous Euclidean isometries, have a non-vanishing current, exhibit a direction of quasisymmetry that is not tangential to the toroidal boundary, and fit within the framework of anisotropic magnetohydrodynamics.
Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models of autism spectrum disorders
Authors: Chan Andrew Man-Lok , Cheung Stanley Kwok-Kuen , Kwok Jacinda , Or Penelope Mei-Yu , Wong Chi Wai , Feng Bo , Choy Kwong Wai , Chang Raymond C.C. , Burbach J. Peter H. , Cheng Alfred Sze-Lok
Published: April 2022

Background: PTEN Hamartoma Tumor Syndrome (PHTS) is characterized by frequent mutation in PTEN gene. PHTS patients have numerous neurological defects including macrocephaly and autism spectrum disorder. While clinical features of PHTS are likely the result of PTEN haploinsufficiency, the role of PTEN gene dosage in driving transcriptomic changes in specific neural cell types is not known. Methods: We performed transcriptomic and proteomic analysis on neural tissues and primary cultures from Pten heterozygous and homozygous knockout mice. Results: We found that somatosensory cortex (SSC) of Pten heterozygous mice are enriched with immune response and oligodendrocyte development Gene Ontology (GO) terms. Parallel proteomic analysis reveals differentially expressed proteins (DEPs) related to dendritic spine development, keratinization and hamartoma signatures. The lack of concordance between transcriptomic and proteomic data prompted us to profile the transcriptomes of specific neural cell types. Overall, Pten homozygous knockout cells have much greater differential expressed genes (DEGs) than Pten heterozygous knockout cells. Pten heterozygous knockout primary astrocytes (AST) are enriched in Extracellular Matrix GO terms while primary cortical neurons (PCN) are enriched with immediate-early genes. In Pten homozygous knockout AST, cilium-related activity is enriched while PCN exhibited downregulation of forebrain neuron generation and differentiation which may lead to disruption of excitatory/inhibitory balance in brain. By integrating DEPs with a pre-filtered DEGs, we identified traits of intelligence and cognitive function, and schizophrenia being enriched, and DEP from AST is significantly associated with intelligence and depression.Limitations: First, bulk tissues were used for transcriptomic and proteomics analysis. Cell type specific expression changes may not be revealed. Second, primary neural cell cultures were used for transcriptomic analysis, which may not reflect the normal physiological conditions.Conclusions: We have uncovered transcriptomic alterations and molecular pathways that may explain neurological disorders associated with PHTS.
Analyzing the role of reoperation in recurrent glioblastoma: A 15-year retrospective study in a single institution
Authors: Jiménez Víctor González , Doval Marta Brell , Domínguez Javier Ibáñez , Salvá José Fuster , Ferrero Lesmes Moratinos , Ruano Daniel Alegre , Lage Sofía López
Published: April 2022

Background: Multiple treatment options at glioblastoma progression exist, including reintervention, reirradiation, additional systemic therapy, and novel strategies. No alternative has been proven to be superior in terms of postprogression survival (PPS). A second surgery has shown conflicting evidence in the literature regarding its prognostic impact, possibly affected by selection bias, and might benefit a sparse subset of patients with recurrent glioblastoma. The present study aims to determine the prognostic influence of salvage procedures in a cohort of patients treated in the same institution over 15 years.Methods: Patients with confirmed primary glioblastoma diagnosed and treated between 2005 and 2019 were selected. To examine the role of reoperation, we intended to create comparable groups, previously excluding all diagnostic biopsies and patients who were not actively treated after the first surgery or at disease progression. Uni-and multivariate Cox proportional hazards regression models were employed, considering reintervention as a time-fixed or time-dependent covariate. The endpoints of the study were overall survival (OS) and PPS.Results: At progression, (n=33) patients received a second surgery, and (n=84) were treated with chemotherapy only. Clinical variables were similar among groups. OS, but not PPS, was superior in the reintervention group. Treatment modality had no impact in our multivariate Cox regression models considering OS or PPS as the endpoint.Conclusions: The association of reoperation with improved prognosis in recurrent glioblastoma is unclear and may be influenced by selection bias. Regardless of our selective indications and high gross total resection rates in second procedures, we could not observe a survival advantage.
Analysis of Fixed and Variable Operating Room (OR) Time Point Efficiency in Partial Nephrectomies: Open Versus Robotic-assisted
Authors: Geldmaker Laura E. , Hasse Christopher H. , Baird Bryce A. , Ericson Christian A. , Myers Amanda A. , Haehn Daniela A. , Anyane-Yeboah Abena N. , Wieczorek Mikolaj A. , Ball Colleen T. , Lyon Timothy D. , Pak Raymond W. , Thiel David D.
Published: April 2022

Objective: To analyze operating room (OR) efficiency by evaluating fixed and variable OR times for open (OPN) and robotic-assisted partial nephrectomies (RAPN).Methods: We analyzed consecutive OPN and RAPN performed by one surgeon over a 24-month period. All patients were placed in the lateral decubitus position and secured with a beanbag regardless of approach. Fixed (nonprocedural) OR times were prospectively collected and defined as: in room to anesthesia release time (IRAT), anesthesia release to cut time (ARCT), and close to wheels out time (CTWO). Variable OR time was procedural cut to close time (CTCT). Comparison of fixed and variable OR time points between OPN and RAPN were performed using the Wilcoxon rank sum test. Results: 146 RAPN and 31 OPN were evaluated from 2019-2020. Median IRAT was similar for RAPN versus OPN [20 min (IQR: 16-25) vs. 20 min (IQR: 16-26), P=0.57]. Median ARCT was longer for RAPN than it was for OPN [40 min (IQR: 36-46) vs. 34 min (IQR: 30-39), P<0.001]. Median CTWO was similar for OPN (12 min, IQR: 9-14) and RAPN (11 min, IQR: 7-15) (P=0.89). Median CTCT was longer for RAPN (202 min, IQR: 170-236) compared to OPN (164 min, IQR: 154-184) (P<0.001).Conclusions: In a single surgeon partial nephrectomy series with the same patient positioning, utilization of robotic technology was associated with longer surgeon operating time as well as less efficient fixed OR times, specifically ARCT.
Human PMSCs derived exosomes alleviate neuropathic pain through miR-26a-5p/Wnt5a in SNI mice model
Authors: Lu Yitian , Zhang Jintao , Zeng Fanning , Wang Peng , Guo Xiangna , Wang Haitao , Qin Zaisheng , Tao Tao
Published: April 2022

Background: Mesenchymal stem cell (MSCs)-derived exosomes are considered as a new cell-free therapy for pain caused by nerve injury, but whether human placental mesenchymal stem cell-derived exosomes relieve pain in sciatic nerve injury and its possible mechanism are still unclear. In this study, we investigated the roles of hPMSCs-derived exosomes and related mechanisms in neuropathic pain.Methods: The spared nerve injury (SNI) mouse model was employed. Intrathecal injection of exosomes or miR-26a-5p agomir was performed on the seventh day of modeling, to study its anti-nociceptive effect. Exosomes’ miRNA sequencing (miRNA-Seq) and bioinformatics analysis were performed to study the downstream mechanisms of miRNAs. RT-qPCR, protein assay and immunofluorescence were used for further validation.Results: A single intrathecal injection of exosomes durably reversed mechanical hypersensitivity in the left hind paw of mice with partial sciatic nerve ligation. Immunofluorescence studies found that PKH26-labeled exosomes were visible in neurons and microglia in the dorsal horn of the ipsilateral L4/5 spinal cord and more enriched in the ipsilateral. According to miRNA-seq results, we found that intrathecal injection of miR-26a-5p agomir, the second high counts microRNA in hPMSCs derived exosome, significantly suppressed neuropathic pain and neuroinflammation in SNI mice. Bioinformatics analysis and dual-luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR-26a-5p. The results showed that overexpression of miR-26a-5p in vivo could significantly reduce the expression level of Wnt5a. In addition, Foxy5, a mimetic peptide of Wnt5a, can significantly reverse the inhibitory effect of miR-26a-5p on neuroinflammation and neuropathic pain, and at the same time, miR-26a-5p can rescue the effect of Foxy5 by overexpression. Conclusion: In conclusion, we reported that hPMSCs derived exosomes as a promising therapy for nerve injury induced neuropathic pain. And we showed that the miR-26a-5p in the exosomes regulated Wnt5a/Ryk/CaMKII/NFAT partly take part in the analgesia through anti-neuroinflammation, which suggests an alleviating pain effect through non-canonical Wnt signaling pathway in neuropathic pain model in vivo.
Prospects of thermotolerant Kluveromyces marxianus for high solids ethanol fermentation of lignocellulosic biomass
Authors: Sengupta Priya , Mohan Ramya , Wheeldon Ian , Kisailus David , Wyman Charles E. , Cai Charles M.
Published: April 2022

Simultaneous Saccharification and Fermentation (SSF) is effective for minimizing sugar inhibition during high solids fermentation of biomass solids to ethanol. However, fungal enzymes used during SSF are optimal between 50–60°C, whereas most fermentative yeast, such as Saccharomyces cerevisiae, do not tolerate temperatures above 37°C. Kluveromyces marxianus variant CBS 6556 is a thermotolerant eukaryote that thrives at 43°C, thus potentially serving as a promising new host for SSF operation in biorefineries. Here, we demonstrate the application of CBS 6556 in SSF configuration to understand its capabilities and limitations as compared to a proven SSF strain, S. cerevisiae D5A. For this study, we first pretreated hardwood poplar chips using Co-Solvent Enhanced Lignocellulosic Fractionation (CELF) to remove lignin and hemicellulose and to produce cellulose-enriched pretreated solids for SSF. Our results demonstrate that although CBS 6556 could not directly outperform D5A, it demonstrated superior growth rates at higher temperatures and higher early stage ethanol productivity. We discovered that CBS 6556’s membrane was particularly sensitive to higher ethanol concentrations causing it to suffer earlier fermentation arrest than D5A. Cross-examination of metabolite data between CBS 6556 and D5A and cell surface imaging suggests that the combined stresses of high ethanol concentrations and temperature to CBS 6556’s cell membrane was a primary factor limiting its ethanol productivity. Hence, we believe K. marxianus to be an excellent host for future genetic engineering efforts to improve membrane robustness in order to achieve higher ethanol productivity and titers, serving as a viable alternative to D5A.
Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy
Authors: Huang Jing , Yu Xin , Liu Yue , Du Chengchao , Zhou Honggui , Yang Yamei , Qu Dacheng
Published: April 2022

Objective: To evaluate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women who underwent hysteroscopic polypectomy.Methods: We conducted a retrospective observational cohort study in a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence, including endometriosis and previous polypectomy history were excluded. A total of 233 women were enrolled in this study, including 64 cases (27.5%) with CE and 169 cases (72.5%) without CE. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. Result(s): The EPs recurrence rates at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8%–37.4%) and 9.5% (95% CI 5.0%–14.0%), respectively, with an overall cure rate of 14.2% (95% CI 9.7%–18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P=0.001). Similarly, the EPs recurrence rate was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6, and 9 months). CE and multiple EPs were risk factors for polyp recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of polyps.Conclusion(s): CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE are needed, and unlike unchangeable factors, CE can be changed by antibiotics treatment. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence.
Workflow to develop 3D designed personalized neonatal CPAP masks using iPhone structured light facial scanning
Authors: Kamath Amika A. , Kamath Marielle J. , Ekici Selin , Stans Anna Sofia , Colby Christopher E. , Matsumoto Jane M. , Wylam Mark E.
Published: April 2022

Background
Continuous positive airway pressure (CPAP) is a common mode of respiratory support used in neonatal intensive care units. In preterm infants, nasal CPAP (nCPAP) therapy is often delivered via soft, biocompatible nasal mask suitable for long-term direct-skin contact and held firmly against face. Limited sizes of nCPAP mask contribute to mal-fitting related complications and adverse outcomes in this fragile population. We hypothesized that custom-fit nCPAP masks will improve the fit with less skin pressure and strap tension improving efficacy and reducing complications associated with nCPAP therapy in neonates.
Methods
After IRB approval and informed consent we evaluated several methods to develop 3D facial models to test custom 3D nCPAP masks. These methods included camera-based photogrammetry, laser scanning and structured light scanning using a Bellus3D Face Camera Pro and iPhone X running either Bellus3D FaceApp for iPhone, or Heges application. This data was used to provide accurate 3D neonatal facial models. Using CAD software nCPAP inserts were designed to be placed between proprietary nCPAP mask and the model infant’s face. The resulted 3D designed nCPAP mask was form fitted to the model face. Subsequently, nCPAP masks were connected to a ventilator to provide CPAP and calibrated pressure sensors and co-linear tension sensors were placed to measures skin pressure and nCPAP mask strap tension.
Results
Photogrammetry and laser scanning were not suited to the neonatal face. However, structured light scanning techniques produced accurate 3D neonatal facial models. Individualized nCPAP mask inserts manufactured using 3D printed molds and silicon injection were effective at decreasing surface pressure and mask strap pressure in some cases by more than 50% compared to CPAP masks without inserts.
Conclusions
We found that readily available structured light scanning devices such as the iPhoneX are a low cost, safe, rapid, and accurate tool to develop accurate models of preterm infant facial topography. Structured light scanning developed 3D nCPAP inserts applied to commercially available CPAP masks significantly reduced skin pressure and strap tension at clinically relevant CPAP pressures when utilized on model neonatal faces. This workflow maybe useful at producing individualized nCPAP masks for neonates reducing complications due to malfit.
Effect of postbiotic supplementation containing heat-killed Lactobacillus salivarius modulates on body weight associated with gut microbiota in a pig model
Authors: Ryu Sangdon , Kyoung Hyunjin , Park Kyeong Il , Oh Sangnam , Song Minho , Kim Younghoon
Published: April 2022

For decades, Lactobacillus has been extensively used as beneficial probiotics because it positively effects on the intestinal health of the host and has been studying its possible serve to treat obesity as well as various diseases. This research aimed to investigate the effects of heat-killed Lactobacillus salivarius 189 (HK LS 189) supplementation on anti-obesity and gut microbiota. A total of 48 pigs were fed either a basal diet or a diet supplemented with HK LS 189 for 4 weeks. The impact of HK LS 189 supplementation on the composition and function of the intestinal microbiota was revealed by 16S rRNA gene sequencing. HK LS 189 supplementation significantly decreased growth performance. Moreover, HK LS 189 supplementation altered the gut microbiota of the pigs by decreasing the proportion of Prevotella and increasing the proportion of Parabacteroides. Beta-diversity analysis showed a significant difference between the two groups. The results support the potential use of HK LS 189 for its anti-obesity effect in pigs through modulation of the gut microbiota. Furthermore, we found changes in the functional pathways of the gut microbiota. The functional pathway study indicated that metabolism and lipid metabolism differed between the two groups. Our data may contribute to understanding the potential use of HK LS 189 for improving the anti-obesity effects.
AIM2 is an potential biomarker associated with the Immune-active Tumor Microenvironment Remodeling and PANoptosis in skin cutaneous melanoma
Authors: Long ShengYong , Zhang Xuan Fen
Published: April 2022

Backgrounds:Absent in melanoma 2 (AIM2) is a crucial developmental regulator for innate immune responses and recent reports suggest its vital function in the process of cancer development and progression, however, the mutations, copy number variations (CNV), methylation, and relationship with the tumor microenvironment (TME), along with the underlying molecular biological processes, remain unclear. Methods: the mutations, CNVs, and methylation patterns of AIM2 in patients with skin cutaneous melanoma (SKCM) were systematically analyzed in this study. Its effects on TME, immunotherapy, and prognoses of SKCM patients were also investigated. According to the findings of the multifactorial Cox regression analysis, a prognostic alignment diagram-based model was constructed. Results: The findings showed that AIM2 expression differed significantly in patients with SKCM. The CNVs and gene methylation patterns affected the level of AIM2 expression, and genetic alterations could influence the tumor immunophenotype. The prognostic alignment diagram model had better predictive efficacy and may improve survival rates in patients. The elevated expression of AIM2 led to enhanced immune responses in SKCM patients and could induce cellular pyroptosis, apoptosis, and necrosis. AIM2 could promote CD8+ T-cell infiltration by activating the PANoptosis pathway and M1 macrophage polarization., and this may be a possible mechanism of its action. In addition, significant associations of AIM2 expression with hot tumor, tumor mutational burden (TMB), immune checkpoint-related genes, and microsatellite instability (MSI), were observed. Conclusions:AIM2 is associated with increased abundance of effector CD8+ T-cells, positive responses to immune checkpoint blockade (ICB) treatment, and improved prognoses. Therefore, it could be a putative enhancer and prognostic biomarker for the treatment of SKCM.
Machine Learning-based ABA treatmentrecommendation and personalization for AutismSpectrum Disorder: An exploratory study
Authors: kohli Manu , AP Prathosh , Kar Arpan Kumar , BANGALORE Anjali
Published: April 2022

Autism spectrum is a brain development conditionthat impairs an individual’s capacity tocommunicate socially and manifests itself throughstrict routines and obsessive-compulsive behavior.Applied behavior analysis (ABA) is thegold-standard treatment for autism spectrumdisorder (ASD). However, as the number of ASDcases increases, there is a substantial shortage oflicensed ABA practitioners, limiting the timelyformulation, revision, and implementation oftreatment plans and goals. Additionally, thesubjectivity of the clinician and a lack ofdata-driven decision-making affect treatmentquality. We address these obstacles by applying twomachine learning algorithms to recommend andpersonalize ABA treatment goals for 29 studyparticipants with ASD. The patient similarity andcollaborative filtering methods predicted ABAtreatment with an average accuracy of 81-84percent, with a normalized discounted cumulativegain of 79-81 percent (NDCG) compared toclinician-prepared ABA treatmentrecommendations. Additionally, we assess the twomodels’ treatment efficacy (TE) by measuring thepercentage of recommended treatment goalsmastered by the study participants. The proposedtreatment recommendation and personalizationstrategy are generalizable to other interventionmethods in addition to ABA and for other braindisorders. This study has been registered as aclinical trial on November 5, 2020 with trailregistration number CTRI/2020/11/028933