Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel PilR/PilS Two-Component System Regulates Necrotic Enteritis Pilus Production in Clostridium perfringens

Clostridium perfringens type G isolates cause necrotic enteritis (NE) in poultry, presenting a major challenge for poultry production in the postantibiotic era. Multiple factors in C. perfringens, including both virulent and nonvirulent, are involved in the development of the disease. ABSTRACT Clostridium perfringens causes necrotic enteritis (NE) in poultry. A chromosomal locus (VR-10B) was previously identified in NE-causing C. perfringens strains that encodes an adhesive pilus (NE pilus), along with a two-component system (TCS) designated here as PilRS. While the NE pilus is important in pathogenesis, the role of PilRS remains to be determined. The current study investigated the function of PilRS, as well as the Agr-like quorum-sensing (QS) system and VirSR TCS in the regulation of pilin production. Isogenic pilR, agrB, and virR null mutants were generated from the parent strain CP1 by insertional inactivation using the ClosTron system, along with the respective complemented strains. Immunoblotting analyses showed no detectable pilus production in the CP1pilR mutant, while production in its complement (CP1pilR+) was greater than wild-type levels. In contrast, pilus production in the agrB and virR mutants was comparable or higher than the wild type but reduced in their respective complemented strains. When examined for collagen-binding activity, the pilR mutant showed significantly lower binding to most collagen types (types I to V) than parental CP1 (P ≤ 0.05), whereas this activity was restored in the complemented strain (P > 0.05). In contrast, binding of agrB and virR mutants to collagen showed no significant differences in collagen-binding activity compared to CP1 (P > 0.05), whereas the complemented strains exhibited significantly reduced binding (P ≤ 0.05). These data suggest the PilRS TCS positively regulates pilus production in C. perfringens, while the Agr-like QS system may serve as a negative regulator of this operon. IMPORTANCE Clostridium perfringens type G isolates cause necrotic enteritis (NE) in poultry, presenting a major challenge for poultry production in the postantibiotic era. Multiple factors in C. perfringens, including both virulent and nonvirulent, are involved in the development of the disease. We previously discovered a cluster of C. perfringens genes that encode a pilus involved in adherence and NE development, along with a predicted two-component regulatory system (TCS), designated PilRS. In the present study, we have demonstrated the role of PilRS in regulating pilus production and collagen binding of C. perfringens. In addition, the Agr-like quorum sensing signaling pathway was found to be involved in the regulation. These findings have identified additional targets for developing nonantibiotic strategies to control NE disease.
Prognostic gene biomarker identification in liver cancer by data mining.

BACKGROUND Liver cancer is a common cancer that enormously threatens the health of people worldwide. With the continuous advances of high-throughput gene sequencing technology and computer data mining technology, researchers can understand liver cancer based on the current accumulation of gene expression data and clinical information. METHODS We downloaded the TCGA data of liver cancer on the cancer-related website (https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/), comprising 438 patients and 20,530 genes. After removing some patients with missing survival data, we collected 397 patients' samples. Our data were collected from a public database without real patient participation. While matching the patient samples in the gene expression spectrum, we attained 330 samples with primary tumors and 50 samples with normal solid tissue. RESULTS After the 330 tumor tissue samples were randomized into two equal-numbered groups (one is a training set, and the other is a test set), we selected 26 gene biomarkers from the training set and validated them in the test set. Based on the selected 26 gene biomarkers, RBM14, ALG11, MAG, SETD3, HOXD10 and other 26 genes were considered independent risk factors for the prognosis of liver cancer, and genes such as GHR significantly affect human growth hormone for liver cancer. The findings discovered that low-risk patients survived remarkably better than the high-risk patients (P<0.001), and the area under the curve (AUC) of receiver operating characteristic curve (ROC) was greater than 0.5. CONCLUSION Our numerical results showed that these 26 gene biomarkers can be used to guide the effective prognostic therapy of patients with liver cancer.
Effect of timeliness incentive nursing on postoperative rehabilitation in patients with cervical spondylotic myelopathy.

OBJECTIVE To explore the effect of timeliness incentive nursing on postoperative rehabilitation of patients with cervical spondylotic myelopathy (CSM). METHODS a total of 104 CSM patients treated in our hospital were recruited, who were evenly divided into two groups according to a random number table method. The control group was given routine nursing, and the research group was given timeliness incentive nursing based on routine nursing. The out-of-bed activity time after surgery, the length of hospital stay, the visual analog scale (VAS) scores before and after intervention, the Japanese Orthopedic Association (JOA) scores, the cervical spine range of motion (ROM), changes of quality of life (QOL), complications, and nursing satisfaction were compared between the two groups. RESULTS After intervention, the out-of-bed activity time and length of hospital stay in the research group were significantly shorter than those of the control group (P<0.001). Compared with before intervention, VAS scores were significantly decreased, while JOA scores and ROM were both considerably increased after intervention in both groups (P<0.001). Of note, the improvement in the research group was more significant compared with the control group. The incidence of complications of the research group was remarkably lower than that of the control group (P<0.05). Compared with before intervention, physiological functions, physiological and emotional responsibilities, social function, mental health, energy, and overall health scores were all significantly increased after intervention in both groups, whereas the physical pain was significantly decreased (P<0.001), and these measures of the research group were higher than those of the control group. The nursing satisfaction in the research group was notably higher than that of the control group (P<0.05). CONCLUSION Timeliness incentive nursing can effectively improve postoperative rehabilitation of patients with CSM, reduce the pain, decrease the incidence of complications, improve the QOL, and increase nursing satisfaction.
Revealing the Origin of Polycyclic Aromatic Hydrocarbons in an Urban Snowpack

Polyciclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants in urban atmosphere. Several PAHs are known carcinogens or are the precursors to carcinogenic daughter compounds. Understanding the contributions of various PAH emission sources is critical to appropriately managing PAH levels in the environment. The sources of PAHs to urban snowpack in Shelekhov city, Eastern Siberia, characterized by extremely high levels of PAH accumulation in snow were determined by using end-member mixing approach. The best potential to distinguish PAH emission sources is exhibited by ratios of PAH pairs of the principal mass 228, 252, and 276. The ratios of PAH pairs were used as tracers of end-member PAH sources. The contributions of sources were calculated using systems of linear equations. The results obtained using ratios of PAH pairs were compared with those obtained using molecular diagnostic ratios. It was shown that the results obtained using diagnostic ratios as tracers are less reliable than the results obtained using the ratios of the sums of PAHs.
N-terminal region is required for functions of the HAM family member

ABSTRACT Shoot meristems contain stem cells, and they sustain growth and development of the above-ground tissues in land plants. The HAIRY MERISTEM (HAM) family genes, encoding GRAS-domain transcriptional regulators, play essential roles in the control of shoot meristem development and stem cell homeostasis in several flowering plants. Similar to other GRAS proteins, the C-terminal regions of HAM family proteins across land plants are conserved, containing signature motifs that define the GRAS domain. In contrast, the N-terminal regions of HAM family proteins display substantial divergence in sequence and length. Whether the variable and divergent N-termini are required for the conserved functions of HAM proteins is unknown. Our recent work showed that CrHAM – the HAM homolog in the fern Ceratopteris richardii was able to replace the role of type-II HAM genes in Arabidopsis, maintaining established shoot apical meristems and promoting the initiation of new stem cell niches. Here, we provide additional information and show that CrHAM contains a much longer N-terminal region compared to Arabidopsis HAM proteins, which is conserved among different fern HAM homologs. The deletion of this region largely compromises the ability of CrHAM to replace the function of Arabidopsis HAM proteins in shoot meristems. These new data together with previous results suggest that, although lacking the sequence conservation among HAM homologs from different plant lineages, the N-termini are important for the conserved functions of HAM family proteins.
Aerosol inhalation of ambroxol hydrochloride combined with terbutaline can promote recovery of children with severe pneumonia.

OBJECTIVE This research aimed to investigate the clinical efficacy of aerosol inhalation of ambroxol hydrochloride combined with terbutaline on children with severe pneumonia, and to evaluate its influence on their immune function and inflammatory level. METHODS Totally 113 severe pneumonia children were included. Thereinto, 55 children in the control group (CG) were treated with terbutaline aerosol inhalation, while 58 in the research group (RG) were given ambroxol hydrochloride on the basis of the CG. Their symptom alleviating time, blood gas parameters, adverse reactions during treatment, clinical efficacy, immune function and inflammatory factors were compared. RESULTS The time of fever clearance time, disappearance of cough and pulmonary rates, chest shadow absorption and hospitalization of children in the RG were shorter than those in the CG. The combined treatment did not increase additional adverse reactions; instead, its effective rate was markedly higher than that in the CG. Further research found that after treatment, the arterial partial pressure of oxygen (PaO2), oxygenation index (OI), CD4+ and CD4+/CD8+, and interleukin-10 (IL-10) levels were dramatically increased, while the arterial partial pressure of carbon dioxide (PaCO2), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-17 (IL-17) and CD8+ levels were obviously increased. In addition, these indexes of children in the RG were obviously better than those in the CG. CONCLUSION Aerosol inhalation of ambroxol hydrochloride combined with terbutaline has a remarkable clinical efficacy on children with severe pneumonia, which can improve their immune function and reduce inflammatory reaction.
Shared decision making in breast cancer screening guidelines: a systematic review of their quality and reporting.

BACKGROUND Shared decision making (SDM) is a key component of evidence-based and patient-centred care. The aim of this study is to systematically review the quality of SDM proposals in clinical practice guidelines (CPGs) and consensus statements (CSs) concerning breast cancer (BC) screening. METHODS Guidances were identified, without language restrictions, using a prospectively planned systematic search (MEDLINE, EMBASE, Web of Science, Scopus and guideline websites) from January 2010 to August 2020. Duplicate data extraction used a 31-item SDM quality assessment tool; reviewer agreement was 98%. RESULTS SDM appeared only in 38 (49.4%) (33/68 CPGs, 4/9 CSs) documents (overall compliance with the quality tool: mean 5.74, IQR 3-8). CPGs and CSs specifically mentioning the term SDM (n = 12) had higher quality (mean 6.8, IQR 4-9 vs. mean 2.1, IQR 0-3; P = 0.001). No differences were found in mean quality comparing CPGs with CSs (3 vs. 1.6; P = 0.634), use of systematic review (4.2 vs. 2.9; P = 0.929) and publication in a journal (4 vs. 1.9; P = 0.094). Guidances with SDM were more recently reported than those without it (mean 41 vs. 57 months; P = 0.042). CONCLUSION More than half of all the guidelines did not meet SDM quality criteria. Those that explored it were more recently reported. There is an urgent need for promoting SDM in guidances concerning BC screening issued by institutions, professional associations and medical journals.
Cyclooxygenase-2 expressed hepatocellular carcinoma induces cytotoxic T lymphocytes exhaustion through M2 macrophage polarization.

OBJECTIVE Due to the tumor immune microenvironment (TIME) complexity and cancer heterogeneity, the clinical outcomes of hepatocellular carcinoma (HCC) are barely elicited from the conventional treatment options, even from the promising anti-cancer immunotherapy. As a suppressive TIME-related marker, the role played by cyclooxygenase-2 (COX-2) in HCC TIME, and its potential effects on anti-cancer T cell immune response remains unknown. In our study, to investigate the COX-2-dependent immune regulation pathway, we verified that the macrophages phenotypes were correlated to COX-2/PGE2 expressions among HCC patients. A multi-cellular co-culture platform containing HCC cells, macrophages, and T cells were established to mimic HCC TIME in vitro and in animal model. M2 macrophage polarization and activated CD8+ T cells exhaustion were observed under high COX-2 levels in HCC cells, with further evaluation using CRISPR/Cas9-based PTGS2 knocking out and COX-2 blockade (celecoxib) treatment controls. PGE2, TGF-β, Granzyme B, and IFN-γ levels were testified by flow cytometry and ELISA to fully understand the mechanism of COX-2 suppressive effects on T cell-based anti-HCC responses. The activation of the TGF-β pathway evaluated by auto-western blot in T cells was confirmed which increased the level of phosphorylated Smad3, phosphorylated Samd2, and FoxP1, leading to T cell de-lymphotoxin. In conclusion, high COX-2-expressing HCC cell lines can induce anti-tumor abilities exhaustion in activated CD8+ T cell through M2 TAMs polarization and TGF beta pathway. COX-2 inhibitors may reduce the inhibitory effect on CD8+ T cells through regulating TAMs in TIME, thus enhance the T cell-based cytotoxicity and improve the prognosis of HCC patients.
Validation of a Spanish Version of the Prolapse and Incontinence Knowledge Questionnaire

Supplemental digital content is available in the text. Objective The objective of this study was to validate a Spanish version of the Prolapse and Incontinence Knowledge Questionnaire (PIKQ). Methods Validation and reliability testing of the Spanish version of the PIKQ was conducted in 2 phases. In the first phase, a translation–back-translation method by 6 bilingual researchers was utilized to generate a final Spanish translation. In the second phase, bilingual women were randomized to complete the Spanish or English version first, followed by the alternate language. Agreement between individual items from English and Spanish versions was assessed by percent agreement and κ statistics. Intraclass correlation coefficients compared overall PIKQ scores and pelvic organ prolapse (POP) and urinary incontinence (UI) subscores. To establish test-retest reliability, we calculated Pearson correlation coefficients. In order to have a precision of 10% for 90% agreement, so that the lower 95% confidence interval would not be less than 80% agreement, 50 bilingual participants were required. Results Fifty-seven bilingual women were randomized and completed both versions of the PIKQ. Individual items showed 74%–97% agreement, good to excellent agreement (κ = 0.6–0.89) for 9 items and moderate agreement (κ = 0.4–0.59) for 14 items between English and Spanish PIKQ versions. Intraclass correlation coefficients of the overall score and POP and UI subscores showed excellent agreement (intraclass correlation coefficient = 0.81–0.91). Pearson correlation coefficients between initial and repeat Spanish scores were high: overall (r = 0.87) and for POP (r = 0.81) and UI subscores (r = 0.77). Conclusions A valid and reliable Spanish version of the PIKQ has been developed to assess patient knowledge about UI and POP.
Using a novel smartphone application for capturing of patient-reported outcome measures among patients with inflammatory arthritis:A randomized, crossover, agreement study

Objectives: In Denmark, patients with inflammatory arthritis (IA) have completed patient-reported outcome measures (PROMs) via touchscreens in the outpatient clinic since 2006. However, current technology makes it possible for patients to use their own smartphone via an application (app) developed for the Danish Rheumatology Database (DANBIO). This study aims to evaluate the agreement of PROMs between the DANBIO app and outpatient touchscreen in patients with IA. Method: Patients with IA (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis) were enrolled in a randomized, crossover, agreement study. Participants answered PROMs through the two device types in a randomized order. Differences in PROM scores with 95% confidence intervals (CIs) were evaluated for similarity according to prespecified equivalence margins. Results: The touchscreen invitation was accepted by 138 patients. Sixty patients (20 with each diagnosis) were included. The difference in Health Assessment Questionnaire Disability Index between the two device types was −0.007 (95% CI −0.043 to 0.030); thus, equivalence was demonstrated. In addition, all other PROMs obtained with the two device types were equivalent, except for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which was within the limits of minimally clinically important difference (MCID). In total, 78.3% preferred the DANBIO app. Conclusion: In patients with IA, equivalence was demonstrated between two device types for all PROMs except BASDAI; however, BASDAI was within the limits of the MCID. Implementation of the DANBIO app is expected to optimize outpatient visits, thereby improving healthcare for the individual patient and society.
Recent pharmacological advances in the repurposing of artemisinin drugs

Artemisinins are a family of sesquiterpene lactones originally derived from the sweet wormwood (Artemisia annua). Beyond their well‐characterized role as frontline antimalarial drugs, artemisinins have also received increased attention for other potential pharmaceutical effects, which include antiviral, antiparsitic, antifungal, anti‐inflammatory, and anticancer activities. With concerted efforts in further preclinical and clinical studies, artemisinin‐based drugs have the potential to be viable treatments for a great variety of human diseases. Here, we provide a comprehensive update on recent reports of pharmacological actions and applications of artemisinins outside of their better‐known antimalarial role and highlight their potential therapeutic viability for various diseases.
Autobiographical recall of a stressful negative event in veterans with PTSD

ABSTRACT Posttraumatic stress disorder (PTSD) is characterised by alterations in autobiographical memory for traumatic and non-traumatic events. Studies that focus on event construction – the ability to search for and identify a specific event – have documented overgeneral memory in PTSD. However, the quality of autobiographical memory also depends on the ability to elaborate on an event once constructed by providing additional details. In a prior study, individuals with PTSD generated as many episodic (event-specific) details as trauma-exposed controls when demands on event construction were minimized, albeit the PTSD group generated more non-episodic details. The current study sought to further characterize PTSD-related alterations in event elaboration by asking participants to describe a stressful negative event specified by the experimenter, thus minimizing event construction demands. Narratives were scored for episodic and non-episodic details and relations with measures of executive function and self-reported avoidance were examined. Compared to controls, the PTSD group generated narratives with equivalent episodic detail but greater non-episodic detail, including semantic information and repeated or extended events. Non-episodic detail generation was associated with greater avoidance but not executive functions. Elaborated non-trauma memories may be perceived as overgeneral in PTSD due to greater generation of non-episodic details, rather than diminished episodic detail.
Cloning and Functional Characterization of a Squalene Synthase from Paris polyphylla var. yunnanensis

Paris polyphylla Smith var. yunnanensis (Franch.) Hand. – Mazz. is a precious traditional Chinese medicine, and steroidal saponins are its major bioactive constituents possessing extensive biological activities. Squalene synthase (SQS) catalyzes the first dedicated step converting two molecular of farnesyl diphosphate (FDP) into squalene, a key intermediate in the biosynthetic pathway of steroidal saponins. In this study, a squalene synthase gene (PpSQS1) was cloned and functionally characterized from P. polyphylla var. yunnanensis, representing the first identified SQS from the genus Paris. The open reading frame of PpSQS1 is 1239 bp, which encodes a protein of 412 amino acids showing high similarity to those of other plant SQSs. Expression of PpSQS1 in Escherichia coli resulted in production of soluble recombinant proteins. Gas chromatography‐mass spectrometry analysis showed that the purified recombinant PpSQS1 protein could produce squalene using FDP as a substrate in the in vitro enzymatic assay. qRT‐PCR analysis indicated that PpSQS1 was highly expressed in rhizomes, consistent with the dominant accumulation of steroidal saponins there, suggesting that PpSQS1 is likely involved in the biosynthesis of steroidal saponins in the plant. The findings lay a foundation for further investigation on the biosynthesis and regulation of steroidal saponins, and also provide an alternative gene for manipulation of steroid production using synthetic biology.
Ergogenic Effects of Sodium Bicarbonate Supplementation on Middle-, But Not Short-Distance Swimming Tests: A Meta-Analysis

Abstract This meta-analysis explored the effects of sodium bicarbonate supplementation on swimming performance. Seven databases were searched to find relevant studies. A random-effects meta-analysis of standardized mean differences (SMD) was performed to analyze the data. Nine studies were included in the review. There was no significant difference between placebo and sodium bicarbonate when considering data from all included studies (SMD: −0.10; p = 0.208) or in the subgroup analysis for 91.4-m and 100-m swimming tests (SMD: 0.11; p = 0.261). In the subgroup analysis for 200-m and 400-m swimming tests, there was a significant ergogenic effect of sodium bicarbonate (SMD: −0.22; p < 0.001; −1.3%). Overall, these results suggest that sodium bicarbonate ingestion improves performance in 200-m and 400-m swimming events. The ergogenic effects of this supplement were small, but they may also be of substantial practical importance given that placings in swimming competitions are commonly determined by narrow margins.