bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Efficient System for Intestinal On-site Butyrate Production Using Novel Microbiome-Derived Esterases
Authors: Jung Dah Hyun , Yong Ji Hyun , Hwang Wontae , Yoon Mi Young , Yoon Sang Sun 
Published: February 2021

Abstract
Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5,760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned Escherichia coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.