bluuebunny/crossref_metadata_2025 huggingface dataset:
RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent
Authors: Wang Xin , Tian Linli , Li Yushan , Wang Jingting , Yan Bingrui , Yang Like , Li Qiuying , Zhao Rui , Liu Ming , Wang Peng , Sun Yanan
Published: February 2021

Background: Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood. Methods: The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability. Results: The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a “writer” of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent. Conclusion: Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.
mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus
Authors: Petrasek Tomas , Vojtechova Iveta , Klovrza Ondrej , Tuckova Klara , Vejmola Cestmir , Rak Jakub , Sulakova Anna , Kaping Daniel , Bernhardt Nadine , de Vries Petrus , Otahal Jakub , Waltereit Robert
Published: February 2021

Background: Tuberous Sclerosis Complex (TSC), a multi-system genetic disorder often associated with Autism Spectrum Disorder (ASD), is caused by mutations of TSC1 or TSC2, which lead to constitutive overactivation of mammalian Target of Rapamycin (mTOR). In several Tsc1+/- and Tsc2+/- animal models, cognitive and social behavior deficits were reversed by mTOR inhibitors. However, phase II studies have not shown amelioration of ASD and cognitive deficits in individuals with TSC during mTOR inhibitor therapy. We asked here if developmental epilepsy, common in the majority of individuals with TSC, but absent in most animal models, could explain the discrepancy. Methods: At postnatal day P12, developmental status epilepticus (DSE) was induced in male Tsc2+/- (Eker) and wild-type rats, establishing four experimental groups including controls. In adult animals (n = 36), behavior was assessed in the paradigms of social interaction test, elevated plus-maze, light-dark test, Y-maze and novel object recognition. The testing was carried out before medication (T1), during a 2-week treatment with the mTOR inhibitor everolimus (T2) and after an 8-week washing-out (T3). Electroencephalographic (EEG) activity was recorded in a separate set of animals (n = 18). Results: Both Tsc2+/- mutation and DSE caused social behavior deficits and epileptiform EEG abnormalities (T1). Everolimus led to persistent improvement of the social deficit induced by Tsc2+/-, while deficits related to DSE did not respond to everolimus (T2, T3). Conclusions: These findings may contribute to an explanation why ASD symptoms in individuals with TSC, where comorbid early-onset epilepsy is common, were in clinical studies not reliably ameliorated by mTOR inhibitors.
Sondheimer oscillations as a probe of non-ohmic flow in type-II Weyl semimetal WP2
Authors: Delft Maarten van , Wang Yaxian , Putzke Carsten , Oswald Jacopo , Varnavides Georgios , Garcia Christina , Guo Chunyu , Schmid Heinz , Süβ Vicky , Borrmann Horst , Diaz Jonas , Sun Yan , Felser Claudia , Gotsmann Bernd , Narang Prineha , Moll Philip
Published: February 2021

As conductors in electronic applications shrink, microscopic conduction processes lead to strong deviations from Ohm’s law. Depending on the length scales of momentum conserving (lMC) and relaxing (lMR) electron scattering, and the device size (d), current flows may shift from ohmic to ballistic to hydrodynamic regimes and more exotic mixtures thereof. So far, an in situ, in-operando methodology to obtain these parameters self-consistently within a micro/nanodevice, and thereby identify its conduction regime, is critically lacking. In this context, we exploit Sondheimer oscillations, semi-classical magnetoresistance oscillations due to helical electronic motion, as a method to obtain lMR in micro-devices even when lMR>>d. This gives information on the bulk lMR complementary to quantum oscillations, which are sensitive to all scattering processes. We extract lMR from the Sondheimer amplitude in the topological semi-metal WP2, at elevated temperatures up to T~50 K, in a range most relevant for hydrodynamic transport phenomena. Our data on μm-sized devices are in excellent agreement with experimental reports of the large bulk lMR and thus confirm that WP2 can be microfabricated without degradation. Indeed, the measured scattering rates match well with those of theoretically predicted electron-phonon scattering, thus supporting the notion of strong momentum exchange between electrons and phonons in WP2 at these temperatures. These results conclusively establish Sondheimer oscillations as a quantitative probe of lMR in micro-devices in studying non-ohmic electron flow.
The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations
Authors: Qi Song , Cross Logan , Wise Toby , Sui Xin , O'Doherty John , Mobbs Dean
Published: February 2021

Humans, like many other animals, pre-empt danger by moving to locations that maximize their success at escaping future threats. Here, we test the idea that spatial margin of safety (MOS) decisions, a form of prospective avoidance, result in participants placing themselves closer to safer locations when facing more unpredictable threats. Using multivariate pattern analysis on fMRI data collected while subjects engaged in MOS decisions with varying attack location predictability, we show that while the hippocampus encodes MOS decisions across all types of threat, a vmPFC anterior-posterior gradient tracked threat predictability. The posterior vmPFC encoded for more unpredictable threat and showed functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings suggest that when pre-empting danger, the anterior vmPFC may provide a safety signal, possibly via predictable positive outcomes, while the posterior vmPFC drives prospective danger signals.
Engineered CRISPR/Cas12a Enables Rapid SARS-CoV-2 Detection
Authors: Nguyen Long , Rananaware Santosh , Pizzano Brianna , Stone Brandon , Jain Piyush
Published: February 2021

The coronavirus disease (COVID-19) caused by SARS-CoV-2 has swept through the globe at an unprecedented rate. CRISPR-based detection technologies such as DETECTR, SHERLOCK, and others have emerged as a rapid and affordable platform that can shape the future of diagnostics. Recently, we reported engineered crRNAs for Cas12a, called ENHANCE, that enables enhanced detection of nucleic acids. Here we report development, clinical validation, and advancement of ENHANCE platform for detecting SARS-CoV-2. With an RT-LAMP pre-amplification step, ENHANCE detects samples down to a single copy with 95% accuracy and shows high specificity towards various isolates of SARS-CoV-2 against 31 highly similar and common respiratory pathogens. Utilizing LbCas12a-mediated trans-cleavage activity, ENHANCE works robustly in a wide range of magnesium concentration (3 mM-13 mM), allowing for further assay optimization. Additionally, ENHANCEv2 is developed to further improve the previously reported ENHANCE. ENHANCEv2 employs mutated LbCas12aD156R, engineered chimeric DNA-extended crRNA, and a dual reporter for both fluorescence-based reporter assay and lateral flow assay. Both ENHANCE and ENHANCEv2 are validated in 62 clinical nasopharyngeal swabs, showing 60/62 (96.7%) agreement with RT-qPCR results, and using only 5 µL of sample and 20 minutes of CRISPR reaction. Lateral flow assay on paper strips displays 100% agreement with fluorescence-based reporter assay in the clinical validation. Following a 30-minute pre-amplification RT-LAMP step, the lyophilized ENHANCEv2 is shown to achieve high sensitivity and specificity while reducing CRISPR reaction time to as low as 3 minutes and maintaining its detection capability upon storage at room temperature for several weeks.
Population dynamics in the Japanese Archipelago since the Pleistocene
Authors: Mizuno Fuzuki , Gojobori Jun , Kumagai Masahiko , Baba Hisao , Taniguchi Yasuhiro , Kondo Osamu , Matsushita Masami , Matsushita Takayuki , Matsuda Fumihiko , Higasa Koichiro , Hayashi Michiko , Wang Li , Kurosaki Kunihiko , Ueda Shintaroh
Published: February 2021

The Japanese Archipelago is widely covered with acidic soil made of volcanic ash, an environment which is detrimental to the preservation of ancient biomolecules. More than 10,000 Palaeolithic and Neolithic sites have been discovered nationwide, but few skeletal remains exist and preservation of DNA is poor. Despite these challenging circumstances, we succeeded in obtaining a complete mitogenome sequence from Palaeolithic human remains. We also obtained those of Neolithic (hunting-gathering Jomon and the farming Yayoi cultures) remains, and over 2,000 present-day Japanese. The Palaeolithic mitogenome is potentially an ancestral type of haplogroup M, suggesting it is not only connected to present-day Japanese but also present-day East Asians. There were no changes in the gene pool from the hunting-gathering (Jomon) to the farming cultures (Yayoi), and this is different from in Europe, where there was no genetic continuity between hunter-gatherers and farmers. We also found that a vast increase of population size happened and has continued since the Yayoi period, characterized with paddy rice farming. It means that the cultural transition, i.e. rice agriculture, had significant impact on the demographic history of Japanese population.
New Series of Ternary Metal Chloride Superionic Conductors for High Performance All-Solid-State Lithium Batteries
Authors: Liang Jianwen , Maas Eveline van der , Luo Jing , Li Xiaona , Chen Ning , Adair Keegan , Li Weihan , Hu Yongfeng , Li Junjie , Zhang Li , Zhao Shangqian , Lu Shigang , Wang Jiantao , Huang Huan , Parnell Steven , Smith Ronald , Ganapathy Swapna , Wagemaker Marnix , Sun Xueliang
Published: February 2021

Understanding the relationship between structure, ionic conductivity, and synthesis is the key to the development of solid electrolytes for all-solid-state Lithium batteries. Here, we investigate chloride solid electrolytes with compositions Li3 − 3xM1+xCl6 (-0.14 < x ≤ 0.5, M = Tb, Dy, Ho, Y, Er, Tm). When x > 0.04, a trigonal to orthorhombic phase transition occurs in the isostructural Li-Dy-Cl, Li-Ho-Cl, Li-Y-Cl, Li-Er-Cl and Li-Tm-Cl solid electrolytes. The new orthorhombic phase shows a four-fold increase in ionic conductivity up to 1.3×10− 3 S cm− 1 at room temperature for Li2.73Ho1.09Cl6 (x = 0.09) when compared to the trigonal Li3HoCl6. For isostructural Li-Dy-Cl, Li-Y-Cl, Li-Er-Cl and Li-Tm-Cl solid electrolytes, about one order of magnitude increase in ionic conductivities are observed for the orthorhombic structure compared to the trigonal structure. Using the Li-Ho-Cl components as an example, detailed studies of its structure, phase transition, ionic conductivity, air stability and electrochemical stability have been made. Molecular dynamics simulations based on density functional theory reveal that the different cations arrangement in the orthorhombic structure leads to a higher lithium diffusivity as compared to the trigonal structure, rationalizing the improved ionic conductivities of the new Li-M-Cl electrolytes. All-solid-state batteries of In/Li2.73Ho1.09Cl6/NMC811 demonstrate excellent electrochemical performance at both room temperature and − 10°C. As relevant to the vast number of isostructural halide electrolytes, the present structure control strategy provides guidance for the design of novel halide superionic conductors.
Depression, Post-traumatic Stress, Anxiety, and Fear of COVID-19 in the General Population and Health-Care Workers: Prevalence, Relationship, and Explicative Model in Peru
Authors: Villarreal-Zegarra David , Copez-Lonzoy Anthony , Vilela-Estrada: Ana Lucia , Huarcaya-Victoria Jeff
Published: February 2021

Background: This study has two aims. First, determine the fit of the fear model to COVID-19, anxiety, and post-traumatic stress in the general population and health-care workers. Second, determine which model best explains the relationship between depression and the triad of fear, anxiety, and post-traumatic stress in both groups. Method: A cross-sectional study was conducted using self-reported questionnaires for anxiety, fear of COVID-19, depression, and post-traumatic stress. Information was collected from adults living in Lima, the capital and the most populous city in Peru. The explanatory models were evaluated using a structural regression model.Results: A high overall prevalence of depressive symptoms (16%), anxiety (11.7%), and post-traumatic stress (14.9%) were identified. A higher prevalence of depressive, anxious, or stress symptoms was identified in the general population (28.6%) compared to health-care workers (17.9%). The triad model of fear of COVID-19, anxiety, and stress presented adequate goodness-of-fit indices for both groups. A model was identified that manages to explain depressive symptoms in more than 70% of the general population and health-care workers, based on the variables of the triad (CFI=0.94; TLI=0.94; RMSEA=0.06; SRMR=0.06). Limitations: The prevalence estimates relied on self-reported information. Other variables of interest, such as intolerance to uncertainty or income level, could not be evaluated. Conclusions: Our study proposes and tests one model that explains more than 70% of depressive symptoms. This explanatory model can be used in health contexts and populations to determine how emotional factors can affect depressive symptoms. Keywords: Depression, post-traumatic stress, anxiety, fear of COVID-19, Peru
Regional cerebral blood flow decline can predict atrophy in Alzheimer’s disease spectrum
Authors: Nabizadeh Fardin , Rostami Mohammad Reza , Balabandian Mohammad
Published: February 2021

According to MRI findings, brain atrophy and structural changes play important roles as valid biomarkers for Alzheimer’s Disease (AD) and can support the clinical diagnosis of AD. A decline in the regional cerebral blood flow (rCBF) is believed to be one of the initial changes in the AD continuum. Some studies revealed an association between the amyloid beta (Aβ) and rCBF pattern and suggested that reduced rCBF is an early consequence of neural death prior to considerable grey matter loss. Therefore, in the present study, we investigated the association between rCBF and brain structural changes in three groups of individuals, that is, control (CN), MCI, and AD groups. Our findings revealed a wide spread significant correlation between the rCBF and structural changes, including cortical volume, subcortical volume, surface area, and thickness in all groups after adjusting for age, sex, and APOE genotyping status. According to the present results, CBF might predict future structural changes and cause neurodegeneration associated with AD development, regardless of Aβ or tau accumulation.
Management of Enterococcal Catheter-associated Bloodstream Infections in Patients with Cancer
Authors: Awadh Hesham , Chaftari Anne-Marie , Khalil Melissa , Fares Johnny , Jiang Ying , Deeba Rita , Ali Shahnoor , Hachem Ray , Raad Issam
Published: February 2021

Objective
Enterococcus species are the third most common organisms causing central line-associated bloodstream infections (CLABSIs). The management of enterococcal CLABSI, including the need for and timing of catheter removal, is not well defined. We therefore conducted this study to determine the optimal management of enterococcal CLABSI in cancer patients.
Methods
We reviewed data for 542 patients diagnosed with Enterococcus bacteremia between September 2011 to December 2018. After excluding patients without an indwelling central venous catheter, we classified the remaining 397 patients into 3 groups: Group 1 consisted of patients with CLABSI with mucosal barrier injury (MBI), Group 2 included patients with either CRBSI or CLABSI without MBI, and Group 3 consisted of patients who did not meet the CDC criteria for CLABSI. The impact of early (< 3 days after bacteremia onset and late (3–7 days) catheter removal was compared. The composite primary outcome included absence of microbiologic recurrence, 90-day infection-related mortality, and 90-day infection-related complications.
Results
Among patients in Group 2, those whose catheters were removed within 3 days of bacteremia onset was associated a better overall outcome than those whose catheters were removed later between days 3 to 7 (success rate 88% vs 63%). However, those who had catheters retained beyond 7 days had a similar successful outcome than those who had early catheter removal. Early CVC removal in in non-CLABSI cases (group-3) was not associated with higher success rates.
Conclusion
If removal of central venous catheters is clinically indicated in patients with enterococcal CLABSI earlier removal in less than 3 days may be associated with better outcomes.
Pre-Operative Fluid Resuscitation in the Emergency General Surgery Septic Patient: Does it Really Matter?
Authors: Moran Benjamin J , Major Erin , Kufera Joseph A , Tisherman Samuel A , Diaz Jose
Published: February 2021

Objective: Emergency general surgery (EGS) patients presenting with sepsis remain a challenge. The Surviving Sepsis Campaign recommends a 30 mL/kg fluid bolus in these patients, but recent studies suggest an association between large volume crystalloid resuscitation and increased mortality. The optimal amount of pre-operative fluid resuscitation prior to source control in patients with intra-abdominal sepsis is unknown. This study aims to determine if increasing volume of resuscitation prior to surgical source control is associated with worsening outcomes. Methods: We conducted an 8-year retrospective chart review of EGS patients undergoing surgery for abdominal sepsis within 24 hours of admission. Patients in hemorrhagic shock and those with outside hospital index surgeries were excluded. We grouped patients by increasing pre-operative resuscitation volume in 10 ml/kg intervals up to >70 ml/kg and later grouped them into <30ml/kg or ≥30ml/kg. A relative risk regression model compared amounts of fluid administration. Mortality was the primary outcome measure. Secondary outcomes were time to operation, ventilator days, and length of stay (LOS). Groups were compared by quick Sequential Organ Failure Assessment (qSOFA) and SOFA scoring systems. Results: Of the 301 patients included, the mean age was 55, 51% were male, 257 (85%) survived to discharge. With increasing fluid per kg (<10 to <70ml/kg), there was an increasing mortality per decile, 8.8% versus 31.6% (p=0.004). Patients who received <30 mL/kg had lower mortality (11.3 vs 21%) than those who received >30 ml/kg (p=0.02). These groups had median qSOFA scores (1.0 vs. 1.0, p=0.06). There were no differences in time to operation (6.1 vs 4.9 hours p=0.11), ventilator days (1 vs 3, p=0.08), or hospital LOS (8 vs 9 days, p=0.57). Relative risk regression correcting for age and physiologic factors showed no significant differences in mortality between the fluid groups. Conclusions: Greater pre-operative resuscitation volumes were initially associated with significantly higher mortality, despite similar organ failure scores. However, fluid volumes were not associated with mortality following adjustment for other physiologic factors in a regression model. The amount of pre-operative volume resuscitation was not associated with differences in time to operation, ventilator days, ICU or hospital LOS.
Relaparotomy Post Cesarean Delivery: Characteristics and Risk Factors.
Authors: Weissmann-Brenner Alina , Eran Barzilay , Raanan Meyer , Gabriel Levin , Danielle Harmatz , Amal Alakeli , Noam Domniz , Israel Yoles
Published: February 2021

Purpose: Relaparotomy following cesarean delivery (CD) is performed at a rate of 0.2-1% of CD. The objective of the present study was to identify risk factors for relaparotomy following CD, and to examine whether there is a difference in the risk of relaparotomy between CD performed during different daytimes. Methods: A retrospective study including all CD over ten years. Cases that underwent laparotomy within one week following CD were compared to those that did not. CDs for placenta accreta were excluded.Results: Sixty-four patients underwent relaparotomy following CD. In univariate analysis relaparotomy was significantly higher pregnancies following assisted-reproductive technologies (39.1%vs. 16.9%), hypertensive disorders of pregnancy (18.8%vs. 7%), twin pregnancies (29.7%vs. 10%), preterm deliveries (34.4%vs. 17.6%), low birthweight (2815gr vs. 3047gr), placenta previa (7.8% vs. 1.3%) low body mass index (22.4 vs. 24.5) and urgent CD (54.7% vs. 40.8%), especially during the second stage of labor. In a multivariate regression analysis, the adjusted odds ratio for relaparotomy was 10.24 in CD due to placenta previa, and 5.28 in CD performed at the second stage of delivery.At relaparotomy, active bleeding was found in 50 patients (78.1%), nearly half received packed cells, 12.5% developed consumptive coagulopathy, and 17.2% needed hospitalization in the intensive care unit. 6.3% underwent a second relaparotomy, mainly due to bleeding.Conclusion: Hypertensive disease, placenta previa, and urgent CDs mainly those performed at the second stage of labor are risk factors for relaparotomy after CD.
Physical reality in asymmetrical double-slit experiments
Authors: Van Thuan Vo
Published: February 2021

The recent state-of-the-art double-slit experiments with single electrons and single photons seem to emphasize contradictable dilemma concerning the ontological physical reality in quantum physics. Because of the importance of this problem, we propose and perform another modified laser-beam asymmetrical double-slit experiment. In the results, a Feynman condition with closing mask allows to assess qualitatively the interference contributions of photons passing through one or another slit. Moreover, a definite "which-way" phenomenon has been identified with a high experimental confidence. This would be the simplest way without any disturbance of the photon beam to observe simultaneously both their path and momentum in consistency with the quantum statistical concept.
The effect of urban green roof design on beetle biodiversity
Authors: Gonsalves Sydney , Starry Olyssa , Szallies Alexander , Brenneisen Stephan
Published: February 2021

The value of urban green spaces to biodiversity conservation depends on the design and management. The importance of habitat quality and complexity to species diversity has led to the suggestion that habitat design elements—varied substrate depth, greater plant diversity, logs or stones—would support invertebrate diversity on green roofs. To evaluate this possibility, we conducted pit-fall trap sampling on three green roofs of simple design (intended primarily for stormwater management), three habitat roofs, and five ground-level green spaces, in the Portland, Oregon metropolitan area. Beetles (Coleoptera) were sampled as representatives of total invertebrate diversity. Diversity was compared using sample coverage and Hill numbers to account for differences in sample intensity and fundamental differences in species diversity. Both habitat roofs and ground sites consisted of just over 20% native species, while stormwater roofs had about 5% native species, all of which were considered pests. We collected a greater abundance of beetles on the ground compared to roof sites like others have shown. However, when sample completeness is taken into account, habitat roofs had greater Shannon diversity compared to both ground and stormwater roof sites. Habitat roofs had the fewest dominant species representing 5% or more of total abundance, but also the lowest percent of species represented by singletons (27%). These results indicate that green roofs can support different beetle communities compared to those present at ground-level urban green spaces; our results also support previous findings that biodiverse design can reliably increase green roof diversity compared to more simply designed roofs.
Detection of Plasmodium Falciparum in Laboratory and Naturally Infected Mosquitoes Using Near-infrared Spectroscopy
Authors: Da Dari F. , McCabe Ruth , Somé Bernard M. , Esperança Pedro M. , Sala Kasia , Blight Josua , Blagborough Andrew M. , Dowell Floyd , Yerbanga Serge R. , Lefèvre Thierry , Mouline Karine , Dabiré Roch K. , Churcher Thomas S.
Published: February 2021

There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
Study on the Mechanism of Salvia Miltiorrhiza Polysaccharides in Relieving Liver Injury of Broilers Induced by Fluorophenicol
Authors: Geng Yumeng , Lu Chunyu , Jin Guozhong , Li Shuying , Cui Yuqing , Han Chao , Shi Wanyu , Bao Yongzhan
Published: February 2021

In order to explore the transcriptomics and proteomics targets and pathways of Salvia miltiorrhiza polysaccharides (SMPs) alleviating florfenicol (FFC)-induced liver injury in broilers,60 1-day-old broilers were randomly divided into 3 groups: control group ( GP1) was fed tap water, FFC model (GP2) was given tap water containing FFC 0.15 g/L, and SMPs treatment group (GP3) was given tap water containing FFC 0.15 g/L and SMPs 5 g/L.Starting from 1 day of age, the drug was administered continuously for 5 days. On the 6th day, blood was collected from the heart and the liver was taken. Then 3 chickens were randomly taken from each group, and their liver tissues were aseptically removed and placed in an enzyme-free tube. Using high-throughput mRNA sequencing and TMT-labeled quantitative proteomics technology, the transcriptome and proteome of the three groups of broiler liver were analyzed respectively. The results of the study showed that the liver tissue morphology of the chicks in the GP1 and GP3 groups was complete, and there were no obvious necrotic cells in the liver cells. The liver tissue cells in the GP2 group showed obvious damage, the intercellular space increased, and the liver cells showed extensive vacuolation and steatosis. Compared with the GP1 group, the daily gain of chicks in the GP2 group was significantly reduced (P < 0.0 5 or P < 0.01). Compared with the GP2 group, the GP3 group significantly increased the daily gain of chicks (P <0.0 5 or P <0.01). Compared with the GP1 group, the serum levels of ALT, AST, liver LPO, ROS and IL-6 in the GP2 group were significantly increased (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4 and IL-10 in the liver were significantly decreased (P < 0.0 5 o r P < 0.01). After SMPs treatment, the serum levels of ALT, AST, liver LPO, ROS and IL-6 were significantly reduced (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4 and IL-10 in the liver were significantly increased (P < 0.0 5 or P < 0.01). There were 380 mRNA and 178 protein differentially expressed between GP2 group and GP3 group. Part of DEGs was randomly selected for QPCR verification, and the expression results of randomly selected FABP1, SLC16A1, GPT2, AACS and other genes were verified by QPCR to be consistent with the sequencing results, which demonstrated the accuracy of transcriptation-associated proteomics sequencing. The results showed that SMPs could alleviate the oxidative stress and inflammatory damage caused by FFC in the liver of chicken and restore the normal function of the liver. SMPs may alleviate the liver damage caused by FFC by regulating the drug metabolism - cytopigment P450, PPAR signaling pathway, MAPK signaling pathway, glutathione metabolism and other pathways.
Model-Free Adaptive Nonlinear Control of the Absorption Refrigeration System
Authors: Dong Na , Lv Wenjin , Zhu Shuo , Gao Zhong-ke , Grebogi Celso
Published: February 2021

Based on the model-free adaptive control (MFAC) theory, the temperature tracking control problem of single-effect LiBr/H 2 O absorption chiller is explored. Due to the complex nonlinearity and strong coupling characteristics of the absorption refrigeration system, model-free adaptive control strategy is designed for its temperature tracking control. Nevertheless, the traditional model-free adaptive control has a slow tracking speed and poor denoising ability. In order to improve its control effect, output error rate is added to the objective function and new control laws of model-free adaptive control with output error rate (MFAC-OER) have been derived through an exhaustive convergence and stability analysis. The input and output information of the absorption refrigeration system, namely the hot water pump frequency and frozen water outlet water temperature, are combined. The data model of the absorption refrigeration system is subsequently deduced using a compact format dynamic linearization method. Next, based on the single effect absorption chiller experimental platform in our laboratory, its sixth-order dynamic model is built. Finally, the effectiveness and practicability of the improved control strategy are validated by numerical simulations and experimental operating data from our laboratory as well as by the dynamical model of the absorption chiller.
One-year Incidence and Standardized Mortality Rates for Esophageal Squamous Cell Carcinoma in Uganda
Authors: Okello Samson , BYARUHANGA Emmanuel B. , LUMORI Boniface Amanee Elias , AKELLO Suzan Joan , DWOMOH Emmanuel , OPIO Christopher Kenneth , OCAMA Ponsiano , MUYINDIKE Winnie R. , DAVID Christiani C. , COREY Kathleen E.
Published: February 2021

Background: Little is known about the survival of patients with esophageal squamous cell cancer in resource limited settings.Objectives: We sought to determine the incidence of one-year all-cause mortality and age-standardized mortality rates for esophageal squamous cell carcinoma in Uganda.Methods: Prospective cohort of 92 participants with histologically confirmed esophageal squamous cell cancer at Mbarara Regional Referral Hospital, southwestern Uganda. Participants were enrolled between January 2018 and March 2020 and followed until death. We used Kaplan-Meier methods to determine all-cause mortality and median survival time; Cox regression to determine predictors of survival; and determined age-standardized mortality rates (SMR) using the WHO standard population. Results: All 92 participants contributed a total 353.8 months at risk, 89 (96.7%) died representing an incidence rate of 251.5 (95% CI 204.3, 309.6) per 1000 person-months. The difference in the one-year risk of all-cause mortality among men and women was negative 6.4 percentage points. The overall SMR was 9.96 (95%CI 7.63, 12.29) per 100,000 and median survival time was 3.03 (95% CI 2.60, 3.47), shortest (1.77 months) among men younger than 45 and longest (7.77 months) among women aged 75 years or greater. In a fully adjusted model, high socioeconomic status predicted longer survival while increasing age and low socioeconomic status predicted shorter survival.Conclusion: After diagnosis, the one-year incidence rates of all-cause mortality and age-standardized mortality rates among ESCC patients in rural Uganda are high. Initiatives to improve access to oncology care for diagnosis and treatment should be prioritized to improve overall survival.
Phase-Separating Peptides for Direct Cytosolic Delivery and Redox-Activated Release of Macromolecular Therapeutics.
Authors: Sun Yue , Lau Sze Yi , Lim Zhi Wei , Chang Shi Chieh , Ghadessy Farid , Partridge Anthony , Miserez Ali
Published: February 2021

Biomacromolecules are highly promising therapeutic modalities to treat various diseases. However, they suffer from poor cellular membrane permeability, limiting their access to intracellular targets. Strategies to overcome this challenge employ nanoscale carriers that often get trapped in endosome compartments. Here, we report on conjugated peptides forming pH- and redox-responsive coacervate microdroplets by liquid-liquid phase separation (LLPS) that readily cross the cell membrane. A wide range of macromolecules can be quickly recruited within the microdroplets, from small peptides to enzymes as large as 430 kDa to mRNAs. The therapeutic-loaded coacervates bypass endocytosis to directly enter in the cytosol, where they undergo glutathione-mediated release of payload whose bioactivity is retained in the cell, whereas mRNAs exhibit a high transfection efficiency. These peptide coacervates represent a promising platform for intracellular delivery of a large palette of macromolecular therapeutics that have potential in the treatment of various pathologies (e.g. cancers and metabolic diseases), or as carriers for mRNA-based vaccines.
Macaque Neuron Instance Segmentation only with Point Annotations based on Multiscale Fully Convolutional Regression Neural Network
Authors: YOU Zhenzhen , Jiang Ming , Shi Zhenghao , Shi Cheng , Du Shuangli , Liang Jimin , Hérard Anne-Sophie , Jan Caroline , Souedet Nicolas , Delzescaux Thierry
Published: February 2021

In the field of biomedicine, instance segmentation / individualization is important in analyzing the number, the morphology and the distribution of neurons for the whole slide images. Traditionally, biologists apply stereology technique to manually count the number of neurons in the regions of interest and estimate the number in anatomical regions or the entire brain. This is very tedious and time-consuming. In this paper, we propose a multiscale fully convolutional regression neural network combined with competitive region growing technique to individualize size-varying and touching neurons in major anatomical regions of macaque brain. Given that neuron instance or contour annotations are infeasible to obtain in certain regions, such as dentate gyrus where thousands of touching neurons are present, we ask expert to perform point annotations in the center location of neurons (noted as neuron centroids) for training. Thanks to the multiscale resolution achieved by parallel multiple receptive fields and different network depths, our proposed network succeeds in detecting the centroids of size-varying and touching neurons. Competitive region growing is then applied on these centroids to achieve neuron instance segmentation. Experiments on macaque brain data suggest that our proposed method outperform the state-of-the-art methods in terms of neuron instance segmentation performance. To our knowledge, this is the first deep learning research work to individualize size-varying and touching neurons only using point annotations in major anatomical regions in the macaque brain. The cartographic representation of the number and the average orientation of neurons illustrates the synthesis of multi-gigabyte image information in the form of cartography, and shows the characteristics of different anatomical regions from mesoscopic level.
Multi-biological Classification for the Diagnosis of Schizophrenia Using Multi-classifier, Multi-feature Selection and Multi-cross Validation: an Integrated Machine Learning Framework Study
Authors: Ke Peng-fei , Xiong Dong-sheng , Li Jia-hui , Li Shi-jia , Song Jie , Chen Xiao-yi , Zhou Jing , Li Gui-xiang , Chen Jun , Li Xiao-bo , Ning Yu-ping , Wu Feng-chun , Wu Kai
Published: February 2021

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. However, there is relatively little work on multi-biological data for the diagnosis of schizophrenia. This was a cross-sectional study in which we extracted multiple features from three types of biological data including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning, consisting of five classifiers, three feature selection algorithms, and four cross-validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results showed that the performance of the classifier using multi-biological data was better than that of the classifiers using single biological data, with 91.7% accuracy and 96.5% AUC. The most discriminative features (top 5%) for the classification include gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), blood features (superoxide dismutase, monocyte-lymphocyte ratio, and neutrophil), and electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal areas).The proposed integrated framework may be help in understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.
Stromal Interaction Molecule 1 (STIM1) Knock-down Attenuates Migration and Proliferation and Enhances the Expression of Thyroid Specific Proteins in Human Follicular Thyroid Cancer Cells.
Authors: Asghar Muhammad Yasir , Lassila Taru , Paatero Ilkka , Nguyen Van Dien , Kronqvist Pauliina , Zhang Jixi , Slita Anna , Löf Christoffer , Zhou You , Rosenholm Jessica , Törnquist Kid
Published: February 2021

Stromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remained elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared with primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced migration, and expression of promigratory sphingosine 1-phosphate (S1P) and vascular endothelial growth factor-2 (VEGFR2) receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared with normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor (TSHR), thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated migration and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.
Meta-analysis of unipolar and bipolar hemiarthroplasty for femoral neck fractures
Authors: Dong Xiaoming , Li Wei , Qu Wenrui , Xu Meng
Published: February 2021

Background

Femoral neck fracture is a common fracture in the elderly. Improper treatment seriously impacts the patient and could potentially shorten their lifespan. Hemi-arthroplasty is a common treatment for femoral neck fractures, but the selection of unipolar prosthesis or bipolar prosthesis is still a controversial issue. Therefore, we conducted this comprehensive meta-analysis to compare the outcomes of unipolar and bipolar prostheses.
Methods

We searched the PubMed, EMbase, The Cochrane Library, and Web of Science databases for randomized controlled trials and cohort studies comparing unipolar hemiarthroplasty and bipolar hemiarthroplasty. The revised Jadad scale or Newcastle-Ottawa Scale was used to assess the quality of the included studies. After data extraction, continuous data were expressed as standardized mean differences and binary data were expressed as odds ratio. The postoperative infection, mortality, acetabular erosion rate, dislocation rate, and Harris hip score were compared and analyzed with Stata software.
Results

Nineteen studies that compared unipolar and bipolar replacement were included in the meta-analysis. We found no significant differences in the postoperative infection, mortality, dislocation rate, or Harris hip score between unipolar and bipolar replacement. The rate of acetabular erosion in the unipolar group was slightly higher than that in the bipolar group.
Conclusions

Existing studies have revealed that bipolar hemiarthroplasty is superior to unipolar hemiarthroplasty for femoral neck fractures in terms of acetabular erosion.
High-dose Radiation Associated with Improved Survival in IDH-wildtype Low-grade Glioma
Authors: Liu Shuai , Liu Yanwei , Li Guanzhang , Feng Jin , Chen Li , Qiu Xiaoguang
Published: February 2021

PurposeAs molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG.MethodsIn the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy.ResultsIn total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival.ConclusionIn conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.
Regulation Mechanism of Graphene Oxide on the Structure and Mechanical Properties of Bio-Based Gel-Spun Lignin/Poly (Vinyl Alcohol) Fibers
Authors: Jin Yanhong , Jing Yuanyuan , Hu Wenxin , Lin Jiaxian , Cheng Yu , Yang Xiaona , Zhang Kun , Lu Chunhong
Published: February 2021

Lignin has been used as a sustainable and eco-friendly filler in composite fibers. However, lignin aggregation occurred at high lignin content, which significantly hindered the further enhancement of fiber performance. The incorporation of graphene oxide (GO) enhanced the mechanical properties of the lignin/poly(vinyl alcohol) (PVA) fibers and affected their structure. With the GO content increasing from 0 to 0.2%, the tensile strength of 5% lignin/PVA fibers increased from 491 MPa to 631 MPa, and Young's modulus increased from 5.91 GPa to 6.61 GPa. GO reinforced 30% lignin/PVA fibers also showed the same trend. The tensile strength increased from 455 MPa to 553 MPa, and Young's modulus increased from 5.39 GPa to 7 GPa. The best mechanical performance was observed in PVA fibers containing 5% lignin and 0.2% GO, which had an average tensile strength of 631 MPa and a Young’s modulus of 6.61 GPa. The toughness values of these fibers are between 9.9-15.6 J/g, and the fibrillar and ductile fracture microstructure were observed. Structure analysis of fibers showed that GO reinforced 5% lignin/PVA fibers had higher crystallinity, and evidence of hydrogen bonding among GO, lignin, and PVA in the gel fibers was revealed. Further, water resistance and swelling behavior of composite PVA fibers were studied to further evidence the structure change of composite fibers.
Study of The Biomass, Sand, and Biochar Fluidization in A Typical Bed of Fast Pyrolysis
Authors: Vasconcelos David , Júnior José Ferreira , Simonelli George , Santos Luiz Carlos , Pires Carlos Augusto de Moraes
Published: February 2021

Biomass pyrolysis usually occurs in a fluidized bed reactor formed by sand, biomass, and biochar. Dynamics this fluidization differs from that of literature because the biomass is converted continually in biochar. In this study, a series of experiments have been carried out for ternary mixtures of sand, sisal residue, and biochar, varying the compositions and particle size. The tests were based on two simplification hypotheses (steady state and room temperature) due to fast biomass transformation in bed and low Van der Waals force to large particles. The dynamic characteristics determined included the bed pressure drop and bed fluctuation. The single and combined effects of particle size and composition on the final fluidization velocity (Uff) and particle segregation (S) have been analyzed using response surface (RSM). The Uff and S minimum values were found when the variables were in the smallest particle size and composition levels. New correlations were developed for predicting the values of Uff. The error from measured values when using the new correlation was 7.6%, while the literature equation was 9.7%. The present correlations predicted reasonably well predicted the Uff of ternary mixtures in the fast pyrolysis bed.