Miracle-dz/UniFAR-FTUs huggingface dataset:
COG database update: focus on microbial diversity, model organisms, and widespread pathogens

The Clusters of Orthologous Genes (COG) database, also referred to as the Clusters of Orthologous Groups of proteins, was created in 1997 and went through several rounds of updates, most recently, in 2014. The current update, available at https://www.ncbi. nlm.nih. gov/research/COG, substantially expands the scope of the database to include complete genomes of 1187 bacteria and 122 archaea, typically, with a single genome per genus. In addition, the current version of the COGs includes the following new features: (i) the recently deprecated NCBI's gene index (gi) numbers for the encoded proteins are replaced with stable RefSeq or GenBank\ENA\DDBJ coding sequence (CDS) accession numbers; (ii) COG annotations are updated for >200 newly characterized protein families with corresponding references and PDB links, where available; (iii) lists of COGs grouped by pathways and functional systems are added; (iv) 266 new COGs for proteins involved in CRISPR-Cas immunity, sporulation in Firmicutes and photosynthesis in cyanobacteria are included; and (v) the database is made available as a web page, in addition to FTP. The current release includes 4877 COGs. Future plans include further expansion of the COG collection by adding archaeal COGs (arCOGs), splitting the COGs containing multiple paralogs, and continued refinement of COG annotations.
High Sensitivity and High Stability QCM Humidity Sensors Based on Polydopamine Coated Cellulose Nanocrystals/Graphene Oxide Nanocomposite

In this paper, a high sensitivity and high stability quartz crystal microbalance (QCM) humidity sensor using polydopamine (PDA) coated cellulose nanocrystal (CNC)/graphene oxide (GO) (PDA@CNC/GO) nanocomposite as sensitive material is demonstrated. The PDA@CNC was prepared by the self-polymerization action on the surface of CNC, and it acted as filler material to form functional nanocomposite with GO. The material characteristics of PDA@CNC, CNC/GO and PDA@CNC/GO were analyzed by transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR), respectively. The experimental results show that the introduction of PDA@CNC into GO film not only effectively enhanced the sensitivity of GO-based nanocomposite-coated QCM sensor but also significantly maintained high stability in the entire humidity range. The PDA@CNC/GO30-coated QCM humidity sensor exhibited a superior response sensitivity up to 54.66 Hz/% relative humidity (RH), while the change rate of dynamic resistance of the sensor in the humidity range of 11.3–97.3% RH is only 14% that is much smaller than that of CNC/GO-coated QCM. Besides, the effect of the PDA@CNC content on the sensitivity and stability of GO-based nanocomposite-coated QCM humidity was also studied. Moreover, other performances of PDA@CNC/GO-coated QCM humidity sensor, including humidity hysteresis, fast response and recovery and long-term stability, were systematically investigated. This work suggests that PDA@CNC/GO nanocomposite is a promising candidate material for realizing high sensitivity and high stability QCM humidity sensor in the entire humidity detection range.
Application of Instrumented Paddles in Measuring On-Water Kinetics of Front and Back Paddlers in K2 Sprint Kayaking Crews of Various Ability Levels

This study used instrumented paddles to obtain on-water kinetic variables of two-seater (K2) crews during sprint kayaking. A total of 74 male kayakers of various ability levels (national team: 9, recreational club: 38, school team: 27) comprising 39 K2 crews were recruited. Both the front and back paddlers were provided with an instrumented paddle to perform 200-m maximal effort paddling in a reservoir. Force, power, and temporal variables were extracted from the paddle data. Difference among groups were compared using a factorial Analysis of Variance. Results showed that the force, power, and temporal characteristics of the front and back paddlers were similar during maximal effort sprint kayaking. Proficient kayakers produced greater kinetic outputs than less proficient kayakers, while the coordination strategy based on timing differences at key events between the two crew members in a K2 boat was similar across ability levels. These data can be useful for coaches, sport scientists, and athletes in planning and monitoring the training.
Development and validation of a rapid and efficient method for simultaneous determination of mycotoxins in coix seed using one-step extraction and UHPLC-HRMS

ABSTRACT Coix seed is an important food and traditional Chinese medicine in China and other Asian countries. Notably, coix seed is currently being used as a traditional medicine for the treatment of COVID-19 in China. However, coix seeds are generally contaminated by mycotoxins, and this risk cannot be ignored. In this paper, we developed a method that involves direct extraction and UHPLC-HRMS analysis for the simultaneous detection of 24 mycotoxins in coix seeds. UHPLC-HRMS instrument and data acquisition parameters, and the sample pretreatment were optimised. One-step extraction showed several advantages compared to the three commercial solid-phase extraction clean-up methods, including ease of use, reduced time of sample preparation, low cost, good recovery, and acceptable matrix effect. The method validation results indicate that all mycotoxins have good linearity and sensitivity. Recoveries were between 74.2–101.1%, and RSD ranged from 0.1–5.8%. The LOQs for 24 mycotoxins were in the range of 0.5–100 µg/kg. To survey the contamination levels of these mycotoxins in commercial coix seeds, more than 70 samples were collected from Chinese markets and were analysed using the newly developed method. Zearalenone (positive ratio: 98.7%, range:1.1–1562 µg/kg), deoxynivalenol (positive ratio: 87%, range: 8.4–382.5 µg/kg), nivalenol (positive ratio: 85.7%, range: 26.8–828.2 µg/kg), fumonisin B1 (positive ratio: 84.4%, range:2.5–314.5 µg/kg), fumonisin B2 (positive ratio: 75.3%, range:1.6–72.8 µg/kg), fumonisin B3 (positive ratio: 48%, range:1.0–203.6 µg/kg), aflatoxin B1 (positive ratio: 29.9%, range: 0.39–14.7 µg/kg), sterigmatocystin (positive ratio: 29.9%, range: 1.4–51.6 µg/kg), and tenuazonic acid (positive ratio: 19.5%, range 36.1–105.7 µg/kg) were the most frequent mycotoxin contaminants. These results highlight the importance of routine monitoring and control of mycotoxins in coix seeds.
Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder

The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all‐cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics
Deafness mutation D572N of TMC1 destabilizes TMC1 expression by disrupting LHFPL5 binding

Significance The mechanotransduction (MT) complex in auditory hair cells converts the mechanical stimulation of sound waves into neural signals. Our findings reveal previously unrecognized physical and functional interactions of TMC1 and LHFPL5, two critical components of the MT complex, and provide insights into the molecular mechanism by which the D572N mutation in TMC1 causes deafness. Our findings also identify a missing link in the currently known physical organization of the MT micromolecular complex. Furthermore, by demonstrating the power of the microbead-based SiMPull assay for the biochemical examination of rare cells such as hair cells, this study opens up an avenue for the biochemical investigation of MT-complex proteins and other critical nonabundant proteins in hair cells. Transmembrane channel-like protein 1 (TMC1) and lipoma HMGIC fusion partner-like 5 (LHFPL5) are recognized as two critical components of the mechanotransduction complex in inner-ear hair cells. However, the physical and functional interactions of TMC1 and LHFPL5 remain largely unexplored. We examined the interaction between TMC1 and LHFPL5 by using multiple approaches, including our recently developed ultrasensitive microbead-based single-molecule pulldown (SiMPull) assay. We demonstrate that LHFPL5 physically interacts with and stabilizes TMC1 in both heterologous expression systems and in the soma and hair bundle of hair cells. Moreover, the semidominant deafness mutation D572N in human TMC1 (D569N in mouse TMC1) severely disrupted LHFPL5 binding and destabilized TMC1 expression. Thus, our findings reveal previously unrecognized physical and functional interactions of TMC1 and LHFPL5 and provide insights into the molecular mechanism by which the D572N mutation causes deafness. Notably, these findings identify a missing link in the currently known physical organization of the mechanotransduction macromolecular complex. Furthermore, this study has demonstrated the power of the microbead-based SiMPull assay for biochemical investigation of rare cells such as hair cells.
Dopamine, Cognitive Impairments and Second-Generation Antipsychotics: From Mechanistic Advances to More Personalized Treatments

The pharmacological treatment of cognitive impairments associated with schizophrenia is still a major unmet clinical need. Indeed, treatments with available antipsychotics generate highly variable cognitive responses among patients with schizophrenia. This has led to the general assumption that antipsychotics are ineffective on cognitive impairment, although personalized medicine and drug repurposing approaches might scale down this clinical issue. In this scenario, evidence suggests that cognitive improvement exerted by old and new atypical antipsychotics depends on dopaminergic mechanisms. Moreover, the newer antipsychotics brexpiprazole and cariprazine, which might have superior clinical efficacy on cognitive deficits over older antipsychotics, mainly target dopamine receptors. It is thus reasonable to assume that despite more than 50 years of elusive efforts to develop novel non-dopaminergic antipsychotics, dopamine receptors remain the most attractive and promising pharmacological targets in this field. In the present review, we discuss preclinical and clinical findings showing dopaminergic mechanisms as key players in the cognitive improvement induced by both atypical antipsychotics and potential antipsychotics. We also emphasize the concept that these mechanistic advances, which help to understand the heterogeneity of cognitive responses to antipsychotics, may properly guide treatment decisions and address the unmet medical need for the management of cognitive impairment associated with schizophrenia.
Impact of diabetes mellitus on postoperative outcomes in individuals with non-small-cell lung cancer: A retrospective cohort study

Objectives Studies showing that individuals with non-small cell lung cancer (NSCLC) and diabetes mellitus (DM) have reported poor outcomes after pulmonary resection with varying results. Therefore, we investigated the clinical impact of preoperative DM on postoperative morbidity and survival in individuals with resectable NSCLC. Patients and methods Data of individuals who underwent pulmonary resection for NSCLC from 2000 to 2015 were extracted from the database of Kyoto University Hospital. The primary endpoint was the incidence of postoperative complications, and secondary endpoints were postoperative length of hospital stay and overall survival. The survival rate was analyzed using the Kaplan–Meier method. Results A total of 2,219 patients were eligible for the study. The median age of participants was 67 years. Among them, 39.5% were women, and 259 (11.7%) presented with DM. The effect of DM on the incidence of postoperative complications and postoperative length of hospital stay was not significant. Although the 5-year survival rates were similar in both patients with and without DM (80.2% versus 79.4%; p = 0.158), those with DM who had a hemoglobin A1c level ≥ 8.0% had the worst survival. Conclusions In individuals with resectable NSCLC, preoperative DM does not influence the acute phase postoperative recovery. However, poorly controlled preoperative DM could lead to low postoperative survival rates.
The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination

Abstract Meiotic recombination enables reciprocal exchange of genetic information between parental chromosomes and is essential for fertility. MEIOB, a meiosis-specific ssDNA-binding protein, regulates early meiotic recombination. Here we report that the human infertility-associated missense mutation (N64I) in MEIOB causes protein degradation and reduced crossover formation in mouse testes. Although the MEIOB N64I substitution is associated with human infertility, the point mutant mice are fertile despite meiotic defects. Meiob mutagenesis identifies serine 67 as a critical residue for MEIOB. Biochemically, these two mutations (N64I and S67 deletion) cause self-aggregation of MEIOB and sharply reduced protein half-life. Molecular genetic analyses of both point mutants reveal an important role for MEIOB in crossover formation in late meiotic recombination. Furthermore, we find that the MEIOB protein levels directly correlate with the severity of meiotic defects. Our results demonstrate that MEIOB regulates meiotic recombination in a dosage-dependent manner.
The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study.

INTRODUCTION Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. MATERIAL AND METHODS This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. RESULTS In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. CONCLUSIONS The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration.
The ascending aorta and arch in the sights of transcatheter therapy: A time for reappraisal

The ascending aorta and arch have until recently been one of the last bastions of cardiovascular surgery, where life‐threatening diseases impose the need for prompt correction and reversal of the impending adverse prognosis. Though a disease where dogmatic recommendations prevail, with upfront surgical intervention in the mind of every physician, type A acute aortic dissection (AAD) is a subject still blurred with many uncertainties. Endovascular intervention for the treatment of type A AAD is rapidly progressing and utilization of transcatheter therapies in the ascending aorta for treating type A AAD has demonstrated technical success in small studies, low early mortality rates, and relatively acceptable aorta‐related mortality rates in the long term. These findings strengthen the preponderant role of the endovascular heart surgeon in the management of these procedures, where a combination of wire skill training and surgical proficiency encompassing all technical options available makes it distinctive and resourceful, which provides complete resolution to each multicomponent of this disease in one setting, besides the promptness to repair the inherent complications that will accompany these interventions. Transcatheter procedures and open surgery will coexist side by side and be regarded as complementary rather than competing. Substantial more refinement and technological innovation will be necessary before endovascular repair of type A AAD comes to widespread use, the ideal timespan for cardiovascular surgeons to be involved, and prepared to take on the challenges of leading this new enterprise.
Microbe-EDTA mediated approach in the phytoremediation of lead-contaminated soils using maize (Zea mays L.) plants

Abstract In the current study, we investigated the potential of Cronobacter sakazakii- ethylenediaminetetraacetic acid (EDTA) assisted phytoremediation potential of Zea mays L. to remediate lead (Pb)-contaminated soils. The C. sakazakii exhibited various stress tolerance mechanisms via plant growth promoting (PGP) traits, intrinsic extracellular enzyme production and antibiotic resistance. A greenhouse experiment was conducted to examine the dual effects of plant growth promoting endophytic bacteria (PGPEB)-chelator synergy in maize plants under different Pb contaminated soil regimes. C. sakazaii-EDTA (5 mM EDTA kg−1) complex significantly (p < 0.05) enhanced plant growth and biomass (48.91%); chlorophyll a, b and carotenoid contents (27.26%, 25.02% and 42.09%); relative water content (61.33%); proline content (63.60%); root and shoot Pb accumulation capacity (52.31% and 44.71%) in Pb contaminated soils. This may suggest the efficacy of current approach in enhancing plant tolerance capability toward Pb-uptake and phytoremediation capacity. Moreover, maize plants showed differential response to Pb availability in soil-1 (S1; Pb spiked soil, 500 mg kg−1) and soil-2 (S2; aged-contaminated soil) under various treatments. We describe the intriguing role of C. sakazakii-EDTA-maize system for Pb decontamination which can be used as a base line to explore the proposed combinatorial approach for long-term trails under field conditions for reclamation of Pb-contaminated soils. Highlights The PGPEB-EDTA mediated potential of Z. mays against Pb spiked and industrial contaminated soils is noticed. Increased tolerance of Z. mays against Pb in association with C. sakazakii, and EDTA is reported first time. Enhanced accumulation of metals by Z. mays is reported under combined treatment of C. sakazakii, and EDTA. Inoculation of plants with C. sakazakii, and EDTA has positive effects on growth and accumulation of Pb by Z. mays.
Simultaneous LC-MS/MS-Based Quantification of Free 3-Nitro-l-tyrosine, 3-Chloro-l-tyrosine, and 3-Bromo-l-tyrosine in Plasma of Colorectal Cancer Patients during Early Postoperative Period

Quantification with satisfactory specificity and sensitivity of free 3-Nitro-l-tyrosine (3-NT), 3-Chloro-l-tyrosine (3-CT), and 3-Bromo-l-tyrosine (3-BT) in biological samples as potential inflammation, oxidative stress, and cancer biomarkers is analytically challenging. We aimed at developing a liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based method for their simultaneous analysis without an extract purification step by solid-phase extraction. Validation of the developed method yielded the following limits of detection (LOD) and quantification (LOQ) for 3-NT, 3-BT, and 3-CT: 0.030, 0.026, 0.030 ng/mL (LODs) and 0.100, 0.096, 0.098 ng/mL (LOQs). Coefficients of variation for all metabolites and tested concentrations were <10% and accuracy was within 95–105%. Method applicability was tested on colorectal cancer patients during the perioperative period. All metabolites were significantly higher in cancer patients than healthy controls. The 3-NT was significantly lower in advanced cancer and 3-BT showed a similar tendency. Dynamics of 3-BT in the early postoperative period were affected by type of surgery and presence of surgical site infections. In conclusion, a sensitive and specific LC-MS/MS method for simultaneous quantification of free 3-NT, 3-BT, and 3-CT in human plasma has been developed.
Advanced Breast Cancer Definitions by Staging System Examined in the Breast Cancer Surveillance Consortium.

BACKGROUND Advanced breast cancer is an outcome used to evaluate screening effectiveness. The advanced cancer definition resulting in the best discrimination of breast cancer death has not been studied in a breast imaging population. METHODS 52,496 women aged 40-79 years participating in the Breast Cancer Surveillance Consortium diagnosed with invasive cancer were staged using the eighth edition of American Joint Committee on Cancer (AJCC) anatomic and prognostic pathologic systems and Tomosynthesis Mammographic Imaging Screening Trial (TMIST) tumor categories. We calculated the area under the receiver operating characteristic curve (AUC) for predicting 5-year breast cancer death and the sensitivity and specificity for predicting 5-year breast cancer death for three advanced cancer classifications; anatomic stage IIB or higher, prognostic pathologic stage IIA or higher, and TMIST advanced cancer. RESULTS The AUCs for predicting 5-year breast cancer death for AJCC anatomic stage, AJCC prognostic pathologic stage, and TMIST tumor categories were 0.826 (95% confidence interval [CI]=0.817, 0.835), 0.856 (95%CI = 0.846, 0.866), and 0.789 (95%CI = 0.780, 0.797), respectively. AJCC prognostic pathologic stage had statistically significantly better discrimination than AJCC anatomic stage (difference = 0.030, bootstrap 95%CI = 0.024, 0.037) and TMIST tumor categories (difference = 0.067, bootstrap 95%CI = 0.059, 0.075). The sensitivity and specificity for predicting 5-year breast cancer death for AJCC anatomic stage IIB or higher, AJCC prognostic pathologic stage IIA or higher, and TMIST advanced cancer were (72.6%, 76.7%, 96.1%) and (78.9%, 81.6%, 41.1%), respectively. CONCLUSION Defining advanced cancer as AJCC prognostic pathologic stage IIA or higher most accurately predicts breast cancer death. Use of this definition by investigators will facilitate comparing breast cancer screening effectiveness studies.
A 2-Month Follow-Up Study of Psychological Distress among Italian People during the COVID-19 Lockdown

The spread of coronavirus disease 2019 (COVID-19) has called for unprecedented measures, including a national lockdown in Italy. The present study aimed at identifying psychological changes (e.g., changes in depression, stress, and anxiety levels) among the Italian public during the lockdown period, in addition to factors associated with these changes. An online follow-up survey was administered to 439 participants (original sample = 2766), between 28 April and 3 May 2020. A paired sample t-test tested for differences in stress, anxiety, and depression over the period. Multivariate regression models examined associations between sociodemographic variables, personality traits, coping strategies, depression, and stress. Results showed an increase in stress and depression over the lockdown, but not anxiety. Negative affect and detachment were associated with higher levels of depression and stress. Higher levels of depression at the start of the lockdown, as well as fewer coping strategies and childlessness, were associated with increased depression at follow-up, whereas higher levels of stress at the start of the lockdown and younger age were associated with higher stress at follow-up. These results may help us to identify persons at greater risk of suffering from psychological distress as a result lockdown conditions, and inform psychological interventions targeting post-traumatic symptoms.