Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation at the Polymerase Active Site of Mouse DNA Polymerase (cid:2) Increases Genomic Instability and Accelerates Tumorigenesis (cid:1)

Mammalian DNA polymerase (cid:1) (Pol (cid:1) ) is believed to replicate a large portion of the genome and to synthesize DNA in DNA repair and genetic recombination pathways. The effects of mutation in the polymerase domain of this essential enzyme are unknown. Here, we generated mice harboring an L604G or L604K substitution in highly conserved motif A in the polymerase active site of Pol (cid:1) . Homozygous Pold1 L604G/L604G and Pold1 L604K/L604K mice died in utero. However, heterozygous animals were viable and displayed no overall increase in disease incidence, indicative of efﬁcient compensation for the defective mutant polymerase. The life spans of wild-type and heterozygous Pold1 (cid:2) /L604G mice did not differ, while that of Pold1 (cid:2) /L604K mice was reduced by 18%. Cultured embryonic ﬁbroblasts from the heterozygous strains exhibited comparable increases in both spontaneous mutation rate and chromosome aberrations. We observed no signiﬁcant increase in cancer incidence; however, Pold1 (cid:2) /L604K mice bearing histologically diagnosed tumors died at a younger median age than wild-type mice. Our results indicate that heterozy- gous mutation at L604 in the polymerase active site of DNA polymerase (cid:1) reduces life span, increases genomic instability, and accelerates tumorigenesis in an allele-speciﬁc manner, novel ﬁndings that have implications for human cancer.
Board Demographics, Ownership Structure, Intellectual Capital and Company Value

: This study investigates the impact of board demographics (board demographics), ownership structure, and intellectual capital on firm value. Using 120 samples taken proportionally from each industrial sector in the Indonesia Stock Exchange, this study uses balanced-panel data with the GLS (generalized least square) regression method of Random-Effects analysis. The study results found that Board demographics (gender, age, and ethnicity of the director) affect firm value. On the other hand, the ownership structure (managerial ownership, institutional ownership, and community ownership) has no significant impact on firm value. The insignificant result for this variable could be due to the two-tier board system used in Indonesia. This system distinguishes the responsibility between directors and commissioners; thus, the possibility of a conflict of interest arises. Intellectual capital also has a positive and significant impact on firm value (Tobins' Q). and 2009) some on how impacts value in in and and (2007) examined in More research investigating the part of by Weisbach (1991), Yermack (1996), and Wells (1998), Mak and Kusnadi (2005), and the
Efficacy and Safety of Traditional Chinese Medicine Based on the Method of “Nourishing Kidney and Clearing Heat” as Adjuvant in the Treatment of Diabetes Mellitus Patients with Periodontitis: A Systematic Review and Meta-Analysis

Objective The aim of this systematic review and meta-analysis was to assess the efficacy and safety of traditional Chinese medicine based on the method of “nourishing kidney and clearing heat” as an adjuvant in the treatment of diabetes mellitus patients with periodontitis. Methods An electronic literature search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, EMBASE, Web of Science, and Cochrane Library databases for articles published until October 2021. The primary outcomes were probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PLI), and sulcular bleeding index (SBI), while the secondary outcomes were tooth mobility (TM), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), total effective rate, and adverse effects. Results Eleven randomized controlled trials (RCT) were included in the meta-analysis. The pooled results showed PPD (WMD = 1.07, 95%CI: (0.82, 1.33), P < 0.00001, I2 = 89%), CAL (WMD = 0.78, 95%CI: (0.62, 0.93), P < 0.00001, I2 = 58%), PLI (WMD = 0.44, 95%CI: (0.09, 0.79), P=0.01, I2 = 97%), SBI (WMD = 0.87, 95%CI: (0.79, 0.95), P < 0.00001, I2 = 37%), TM (WMD = 0.26, 95%CI: (0.21, 0.30), P < 0.00001, I2 = 31%), HbA1c (WMD = 0.48, 95%CI: (0.28, 0.67), P < 0.00001, I2 = 26%), FBG (WMD = 1.34, 95%CI: (0.96, 1.72), P < 0.00001, I2 = 52%), total effective rate (RR = 1.24, 95%CI: (1.14, 1.34), P < 0.00001, I2 = 0%), and adverse effects (RR = 0.78, 95%CI: (0.20, 3.03), P=0.72, I2 = 0%) in the traditional Chinese medicine based on the method of “nourishing kidney and clearing heat” + routine western medicine treatment (periodontal basic treatment, PBT, with or without antibiotic) group were significantly improved compared to control group, but no significant difference was observed for PLI at 2–3 months and 6 months. Conclusions This review supports traditional Chinese medicine based on the method of “nourishing kidney and clearing heat” as an adjuvant to routine western medicine treatment in the management of diabetes mellitus patients with periodontitis. Within the limits of the evidence, the well-designed, long-term efficacy, and high-quality multicenter RCTs need to be further confirmed.
jDIII/DIAGNOSTIC NUCLEAR MEDICINE Diagnosis of Cirrhosis and Hepatitis by Quantitative Hepatic and Other ReticuIoendotheiiai Clearance Rates

and spleen are usually attempted by qualitative visual assessment of scans: actually, one estimates the rela tive distribution of radioactivity in the reticuloen dothelial (RE ) tissues ( 1) . Measurement of colloid clearance rates was first attempted with blood clear ance curves (2,3) , but more recently external count ing techniques have been employed (4,5). Increased uptake in the spleen relative to the liver, as determined by visual assessment of scans, has been correlated with cirrhosis, carcinoma, ane mia, and diabetes mellitus (6). Decreased splenic uptake, by the same method, has been correlated with RE and hematopoietic neoplasia (6,7). Quan titative techniques have been used to document a reduction in RE clearance in cirrhosis (3â€”5). To our knowledge, no effort has been made to quantitate colloid clearance rates individually for the liver, spleen, and other RE tissues and to categorize dis eases systematically with this information. This paper describes a kinetic radionuclide tech nique for quantitative assessment of colloid clear ance-rate constants for the liver, spleen, and other RE tissues and reports preliminary results that seem to differentiate cirrhosis, fatty metamorphosis, hepa titis, and normal function.
HT_BIM: Parametric modelling for the assessment of risk in historic centers 7HT_BIM: La modellazione parametrica per l’analisi del rischio nei centri storici

The Italian historical centers are “environmental monuments” to protect and preserve. These centers are particularly vulnerable both in terms of seismic and environmentally but also due to the their modification over time. Their management is very complex because of the heterogeneous data both of the unit building and the structural aggregate that the entire urban center. In recent years the parametric system BIM, has been of great help in the design, planning and construction of new buildings. Lately similar models are developed for the analysis and management of heritage buildings. The aim of the research is the design of Historical Town Building Information Modeling (HT_BIM), able to analyze the architectural features, to define the kinematic collapse of structural aggregates and to identify the degradation by wind and sun exposures.
Correlation Between sST2, IL-34 and Mortality in CHF Egyptian Patients

Novel biomarkers such as soluble ST2 (sST2), Interleukin-34 (IL34), some traditional biomarkers as BNP, and TNF-α, could be used in diagnosis and prognosis of patients with chronic heart failure (CHF). This study aimed at evaluating the clinical effect and economic impact values of these above-mentioned biomarkers in CHF patients. 41 CHF stage III patients with LVEF ≤ 40 and thirty healthy control volunteers were recruited and accessed via clinical examination, echocardiography, lipid profile, serum electrolytes, and serum biomarkers. Data showed that, serum levels of the four studied biomarkers were significantly elevated in CHF patient as compared to the control group (P< 0.05). A significant negative correlation was observed between serum levels of these biomarkers and LVEF. A significant positive correlation was observed between CRI-I and CRI-II and total cholesterol, LDL-C, sST2, and IL-34 (P< 0.05). It was found that, sST2 is the most prominent predictor in providing independent and additive prognostic information of mortality (P= 0.043) and the most cost-effective biomarker as compared to EF, IL-34, BNP and TNF-α. Elevated serum levels of these novel and traditional biomarkers may be used as indicator for risk stratification and can also, be applied as independent predictors for the mortality among CHF patients. Using specific and cost-effective biomarker may reduce the numbers of patients requiring echocardiography and may help in early diagnosis that, may help in selecting the evidence-based therapy that, in turn, may modify patient’s outcomes, and useful to follow the effectiveness of the treatment.
NSS_A_369097 1485..1492

Introduction: Joubert syndrome is a rare disorder, characterized by a complex midbrain malformation caused by defects in the structure and/or function of the primary cilium. Case Report: A 15-year-old boy with mild intellectual disability, hypotonia, mild ataxia, and abnormal eye movements diagnosed as having Joubert Syndrome since childhood, was referred to the Sleep Unit because spells of apnea while sleeping. He did not complain of snoring or daytime somnolence. The macro and microstructure of sleep and the comorbidities such respiratory abnormalities, periodic legs movements (PLM) and paroxysmal motor arousals (PA) and minimal motor events (MME) are described for the first time in Joubert syndrome. Results: EEG was normal. Video-polysomnography revealed a nocturnal disturbed sleep and periods of hyperpnea accompanied by body movements and followed by a periodic breathing lasting several minutes with no oxygen desaturation. The arousals provoked by apneas triggered paroxysmal motor events with dystonic movements in the hand and right foot accompanied by a spontaneous Babinski. Brain MRI showed the typical “molar tooth sign”. Conclusion: Joubert syndrome is a heterogeneous disease. Epileptic seizures have been reported in some cases. Video-PSG is mandatory for the identification of nocturnal breathing abnormalities and sleep-related motor paroxysmal episodes.
Unique deep-sea bacterial assemblages thriving on different natural organic matters delivered via in situ incubators

Jianyang Li School of Environmental Science and Engineering, Tianjin University, Tianjin 300387, PR China; School of Environmental Science and Engineering, Tianjin University, Tianjin 300387, PR China. https://orcid.org/0000-0002-2466-6881 Chunming Dong Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources of PR China; State Key Laboratory Breeding Base of Marine Genetic Resources; Key Laboratory of Marine Genetic Resources of Fujian Province, Xiamen 361005, PR China. Qiliang Lai Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources of PR China; State Key Laboratory Breeding Base of Marine Genetic Resources; Key Laboratory of Marine Genetic Resources of Fujian Province, Xiamen 361005, PR China. Zhaobin Huang Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources of PR China; State Key Laboratory Breeding Base of Marine Genetic Resources; Key Laboratory of Marine Genetic Resources of Fujian Province, Xiamen 361005, PR China. Donghui Zhou School of Mechanical Engineering, Hangzhou Dianzi University, Hangzhou 310018, PR China. Linfeng Gong Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources of PR China; State Key Laboratory Breeding Base of Marine Genetic Resources; Key Laboratory of Marine Genetic Resources of Fujian Province, Xiamen 361005, PR China. Guangyi Wang School of Environmental Science and Engineering, Tianjin University, Tianjin 300387, PR China. Zongze Shao (  shaozz@163.com ) Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources of PR China; State Key Laboratory Breeding Base of Marine Genetic Resources; Key Laboratory of Marine Genetic Resources of Fujian Province, Xiamen 361005, PR China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, PR China
Response to reviewers’ comments to the manuscript: ‘ Use of expert elicitation to assign weights to climate and hydrological models in climate impact studies’ (manuscript number hess-2021-597)

The paper uses five case study locations in Europe to test an expert elicitation approach to weighting climate and hydrological models. The study uses a structured expert elicitation approach, involving three stages of individual elicitations and consensus building, supported by some initial training material. The study finds that hydrologists are more willing than climate modellers to articulate model weights, with climate modellers preferring model democracy in the absence of further investigation. The shift in approach from in-person to online, due to the covid-19 pandemic, affected the approach followed away from typical elicitation processes. be risks over-confidence in uncertainty estimates. Abstract. Various methods are available for assessing uncertainties in climate impact studies. Among such methods, model weighting by expert elicitation is a practical way to provide a weighted ensemble of models for specific real-world impacts. 30 The aim is to decrease the influence of improbable models in the results and easing the decision-making process. In this study both climate and hydrological models are analyzed and the result of a research experiment is presented using model weighting with the participation of 6 climate model experts and 6 hydrological model experts. For the experiment, seven climate models are a-priori selected from a larger Euro-CORDEX ensemble of climate models and three different hydrological models are chosen for each of the three European river basins. The model weighting is based on qualitative 35 evaluation by the experts for each of the selected models based on a training material that describes the overall model structure and literature about climate models and the performance of hydrological models for the present period. The expert elicitation process follows a three-stage approach, with two individual elicitations of probabilities and a final group consensus, where the experts are separated into two different community groups: a climate and a hydrological modeller group. The dialogue reveals that under the conditions of the study, most climate modellers prefer the equal weighting of 40 ensemble members, whereas hydrological impact modellers in general are more open for assigning weights to different models in a multi model ensemble, based on model performance and model structure. Climate experts are more open to exclude models, if obviously flawed, than to put weights on selected models in a relatively small ensemble. The study shows that expert elicitation can be an efficient way to assign weights to different hydrological models, and thereby reduce the uncertainty in climate impact. However, for the climate model ensemble, comprising seven models, the elicitation in the 45 format of this study could only reestablish a uniform weight between climate models.
Mechanisms of STIM1 Activation of Store-Independent Leukotriene C 4 -Regulated Ca 2 (cid:1) Channels

We recently showed, in primary vascular smooth muscle cells (VSMCs), that the platelet-derived growth factor activates canonical store-operated Ca 2 (cid:1) entry and Ca 2 (cid:1) release-activated Ca 2 (cid:1) currents encoded by Orai1 and STIM1 genes. However, thrombin activates store-independent Ca 2 (cid:1) selective channels contributed by both Orai3 and Orai1. These store-independent Orai3/Orai1 channels are gated by cytosolic leukotriene C 4 (LTC 4 ) and require STIM1 downstream LTC 4 action. However, the source of LTC 4 and the signaling mechanisms of STIM1 in the activation of this LTC 4 -regulated Ca 2 (cid:1) (LRC) channel are unknown. Here, we show that upon thrombin stimulation, LTC 4 is produced through the sequential activities of phospholipase C, diacylglycerol lipase, 5-lipo-oxygenease, and leukotriene C 4 synthase. We show that the endoplasmic reticulum-resident STIM1 is necessary and sufﬁcient for LRC channel activation by thrombin. STIM1 does not form sustained puncta and does not colocalize with Orai1 either under basal conditions or in response to thrombin. However, STIM1 is precoupled to Orai3 and Orai3/Orai1 channels under basal conditions as shown using Forster resonance energy transfer (FRET) imaging. The second coiled-coil domain of STIM1 is required for coupling to either Orai3 or Orai3/Orai1 channels and for LRC channel activation. We conclude that STIM1 employs distinct mechanisms in the activation of store-dependent and store-independent Ca 2 (cid:1) entry pathways. is universal second messenger that controls a variety of cellfunctionsinhealthanddisease.Innonexcitablecells,most Inthisstudy,weappliedconfocalandForsterresonanceenergy transfer (FRET) imaging, Fura2 Ca 2 (cid:1) imaging, and patch clamp electrophysiology coupled to pharmacology and “erase-and-re-place” approaches to show that thrombin activates store-indepen-dent LRC channels through LTC 4 produced via the sequential catalytic activities of PLC, DAG lipase, 5-lipo-oxygenase (5-LO), and LTC 4 synthase (LTC 4 S). We provide evidence that ER-resi-dent STIM1 is necessary and sufﬁcient for LRC channel activation and that ER-STIM1 is precoupled to Orai3 under basal conditions through the second coiled-coil domain of STIM1.
Microstructure and Mechanical Properties of Ti-6Al-4V Additively Manufactured by Electron Beam Melting with 3D Part Nesting and Powder Reuse Inﬂuences

: To better support the transition to more industrial uses of additive manufacturing, this study examined the use of an Arcam Q20+ industrial 3D printer for producing heavily nested Ti-6Al-4V parts with both in-speciﬁcation (IS) and out of speciﬁcation (OS) oxygen content in reused grade 5 powder chemistries. Both the OS and IS powder chemistries were evaluated to understand their impact on build integrity and on static and fatigue performance. The results from our eval-uations showed that controlling the bed preheat temperature in the Q20+ to relatively low values (326–556 ◦ C) was effective in limiting microstructural coarsening during the long build time and enabled adequate/balanced performance vis à vis the tensile strength and ductility. Overall, the tensile properties of the IS Ti-6Al-4V material in the as-built and machined states fully met the requirements of ASTM F2924-14. By contrast, the ductility was compromised at oxygen levels above 0.2 wt. % (OS) in Ti-6Al-4V produced by EBM. Removal of the surface layer by machining increased the consistency and performance of the IS and OS Ti-6Al-4V materials. The fatigue behaviour of the EBM Ti-6Al-4V material was in the range of properties produced by casting. Due to the strong inﬂuence of both the surface ﬁnish and oxygen content on the fatigue strength, the IS Ti-6Al-4V material exhibited the highest performance, with results that were in the range of parts that had been cast plus hot isostatically pressed.
Screening of Clostridium difficile Isolates for Metallo-Resistant Gene and Extended Spectrum Beta-Lactamases

Clostridium difficile naturally inhabits intestinal tract of animals including humans. Spores of C. difficile are known contaminant in the Environment. Indiscriminate use of antibiotics has led to the emergence of a powerful resistance determinant (known as Metallo resistant genes) in many bacteria worldwide. Multidrug resistant bacteria (MRB) pose threats to health globally. This study aims to determine the distribution of Metallo resistant Clostridium difficile in hospital environment within Yola. A total of 150 surface samples from the hospital wards were collected from Federal Medical Centre, Yola (FMC) and Specialist hospital, Yola (SHY) Adamawa state, Nigeria. Clostridium difficile were recovered by inoculating samples in modified Cycloserine-cefoxitin fructose broth (CCFB) and Cycloserine-cefoxitin fructose agar (CCFA). Screening of isolates for extended spectrum β-lactamase (ESBL) and metallo-β-lactamase enzymes was done by double disc diffusion method and Imipenem-EDTA combined disc test respectively. A total of 18 C. difficile isolates were obtained and found to be extended spectrum β-lactamase (ESBL) positive. 16 (88.89 %) of the Clostridium difficile were found to be metallo-β-lactamase positive. Polymerase chain reaction showed that 11 (61.1%) of the isolates possess bla -IMP metallo resistant gene. This study suggests that multidrug resistant C. difficile with metallo resistant genes are wide spread in hospital settings and there is need for relevant authorities to improve on the sanitization of environment as well as continuous surveillance to hinder C. difficile transmission.
a repository copy of Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Objectives: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the eficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with − 1.0 > bone mineral density (BMD) T-score > − 2.5 (low bone mass) and those with BMD T-score ≤ − 2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36 – 0.71) and signiicantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70% – 5.14%). At the hip, this value was 2.94% (95%CIs = 2.13% – 3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene signiicantly decreases the risk of subsequent clinical vertebral fractures. Conclusion: The bisphosphonates are eficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.