Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of Polymorphisms of Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) Gene and Smoking with the Risk of Rheumatoid Arthritis in Chinese Han People

Background In this study we report on the possible connection between single nucleotide polymorphisms (SNPs) in natural resistance-associated macrophage protein 1 (NRAMP1) gene and the risk of rheumatoid arthritis (RA) in the Chinese Han population. Material/Methods A total of 248 participants consisting of 116 RA cases and 132 healthy individuals were recruited for the current study. Genotyping for NRAMP1 gene polymorphisms was implemented using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The chi-square test was used to detect discrepancies in genotype and allele frequencies between the RA case group and the control group. Odds ratios (ORs) with 95% confidence intervals (CIs) was used to evaluate relative risk of RA. The results were adjusted by logistic regression analysis. Results The TT genotype and T allele in rs17221959 showed dramatically different distribution between RA cases and healthy controls. After adjustment, TT genotype (OR=0.338, 95%CI=0.278–1.214, P=0.028) and T allele (OR=0.608, 95%CI=0.298–0.956, P=0.005) showed close association with reduced risk of RA. For rs1059823, no obvious diversity was uncovered in either genotype or allele distribution between the 2 groups. Interaction analysis showed that smoking decreased the protective function of TT in rs17221959. Conclusions This study suggested that the TT genotype and T allele in rs17221959 decreased RA risk. Smoking could decrease the protective effect of TT.
Tumor Microenvironment-Activated Ultrasensitive Nanoprobes for Specific Detection of Intratumoral Glutathione by Ratiometric Photoacoustic Imaging.

Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellu-lar functions. Precise quantification of GSH via advanced non-invasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable NIR-absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors. This special ratiometric PAI nanoprobe (CR-POM) is synthesized through the self-assembly of croconaine (CR) dye and molybdenum (Mo)-based polyoxometalate (POM) clusters with opposite NIR absorbance change in response to GSH. The resulting amplified ratiometric absorbance (Ab866/Ab700), the relatively low limit of detection (LOD) value (0.51 mM), and the unique acidity-activated self-aggregation contribute to the prolonged intratumoral retention and enhanced tumor accumulation of CR-POM for accurate quantification of intratumoral GSH (0.5-10 mM). Featuring the additional merit of 64Cu radiolabeling for whole-body PET imaging, the smartly designed CR-POM nanoprobe will open new horizons for real-time non-invasive monitoring of biodistribution and simultane-ous accurate quantification of GSH levels especially in tumor and other GSH-related pathophysiological processes.
Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD), and when it causes CKD it is collectively referred to as diabetic kidney disease. One of the newer therapies for managing hyperglycemia is the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) drug class. This review summarizes the effects of GLP‐1RAs in patients with T2DM with CKD and evidence for renoprotection with GLP‐1RAs using data from observational studies, prospective clinical trials, post hoc analyses, and meta‐analyses. Evidence from some preclinical studies was also reviewed. Taken together, subgroup analyses of patients with varying degrees of renal function demonstrated that glycemic control with GLP‐1RAs was not markedly less effective in patients with mild or moderate renal impairment vs that in patients with normal function. GLP‐1RAs were associated with improvements in some cardiorenal risk factors, including systolic blood pressure and body weight. Furthermore, several large cardiovascular outcome studies showed reduced risks of composite renal outcomes, mostly driven by a reduction in macroalbuminuria, suggesting potential renoprotective effects of GLP‐1RAs. In conclusion, GLP‐1RAs effectively reduced hyperglycemia in patients with mild or moderately impaired kidney function in the limited number of studies to date. GLP‐1RAs may be considered in combination with other glucose‐lowering medications because of their ability to lower glucose in a glucose‐dependent manner, lowering their risk for hypoglycemia, while improving some cardiorenal risk factors. Potential renoprotective effects of GLP‐1RAs, and their renal mechanisms of action, warrant further investigation.
Fabrication of Microwave Devices Based on Magnetic Nanowires Using a Laser-Assisted Process

This paper compares two laser-assisted processes developed by the authors for the fabrication of microwave devices based on nanowire arrays loaded inside porous alumina templates. Pros and cons of each process are discussed in terms of accuracy, reproducibility and ease of fabrication. A comparison with lithography technique is also provided. The efficiency of the laser-assisted process is demonstrated through the realization of substrate integrated waveguide (SIW) based devices. A Nanowired SIW line is firstly presented. It operates between 8.5 and 17 GHz, corresponding to the first and second cut-off frequency of the waveguide, respectively. Next, a Nanowired SIW isolator is demonstrated. It shows a nonreciprocal isolation of 12 dB (corresponding to 4.4 dB/cm), observed in absence of a DC magnetic field, and achieved through an adequate positioning of ferromagnetic nanowires inside the waveguide cavity.
Discovery of Immunoproteasome Inhibitors Using Large-Scale Covalent Virtual Screening

Large-scale virtual screening of boronic acid derivatives was performed to identify nonpeptidic covalent inhibitors of the β5i subunit of the immunoproteasome. A hierarchical virtual screening cascade including noncovalent and covalent docking steps was applied to a virtual library of over 104,000 compounds. Then, 32 virtual hits were selected, out of which five were experimentally confirmed. Biophysical and biochemical tests showed micromolar binding affinity and time-dependent inhibitory potency for two compounds. These results validate the computational protocol that allows the screening of large compound collections. One of the lead-like boronic acid derivatives identified as a covalent immunoproteasome inhibitor is a suitable starting point for chemical optimization.
Impact of military service on physical health later in life: a qualitative study of geriatric UK veterans and non-veterans

Objectives Military veterans often experience physical health problems in later life; however, it remains unclear whether these problems are due to military service or are a feature of the ageing process. This study aimed to explore veteran and non-veteran perceptions of the impact of their occupation on their physical well-being later in life. Design Semi-structured qualitative interviews analysed using thematic analysis. Setting Interviews were conducted face-to-face in participants’ homes or via telephone. Participants 35 veterans (≥65 years), 25 non-veterans (≥65 years) were recruited, as well as a close companion of all participants for triangulation (n=60). Results Most veterans reported good physical health later in life which they attributed to the fitness they developed during military service. However, several veterans described challenges in maintaining their desired level of physically activity due to new commitments and limited sports facilities when they left service. Fewer non-veterans had experienced work-related fitness activities or exercise in their civilian jobs. Ongoing physical health difficulties, such as deafness, were perceived to be due to exposure to workplace hazards and appeared more common in veterans compared with non-veterans. Veterans also described greater reluctance than non-veterans to seek medical treatment for physical health difficulties, which could be challenging for close companions who had to provide informal care. Conclusions Military service was largely perceived to be beneficial for physical well-being; although when occupation-related physical health problems were experienced, many veterans were unwilling to seek treatment. These findings may inform clinicians of the needs of older veterans and highlight potential barriers to care.
LVDS Drivers with Pre-emphasis Function

This paper mainly talk about the theory and application of LVDS driver. There are two design method : One ,we can use the resistor to change the current ; the other , use the double current source to provide the current . Resistance-method is the way of using parallel connection to decrease the resistance and increase the current to realize the pre-emphasis ; The double current source method can control one of the current source to unlock or lock to realize the pre-emphasis. The two circuits are implemented using 0.25 μm CMOS process , and get the same result.
Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.
Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy

In recent years, the lymphocyte-specific protein tyrosine kinase (Lck) has emerged as one of the key molecules regulating T-cell functions. Studies using Lck knock-out mice or Lck-deficient T-cell lines have shown that Lck regulates the initiation of TCR signaling, T-cell development, and T-cell homeostasis. Because of the crucial role of Lck in T-cell responses, strategies have been employed to redirect Lck activity to improve the efficacy of chimeric antigen receptors (CARs) and to potentiate T-cell responses in cancer immunotherapy. In addition to the well-studied role of Lck in T cells, evidence has been accumulated suggesting that Lck is also expressed in the brain and in tumor cells, where it actively takes part in signaling processes regulating cellular functions like proliferation, survival and memory. Therefore, Lck has emerged as a novel druggable target molecule for the treatment of cancer and neuronal diseases. In this review, we will focus on these new functions of Lck.
Ethical Leadership and Employees’ Perceptions About Raising Ethical Concerns to Managers in the Veterans Health Administration

Abstract Background: The willingness of employees to proactively give voice to their concerns, including ethical concerns (ethics voice), is critical to improving organizational performance and integrity. In health care, speaking up is vital to ensuring a delivery system centered on patient safety and quality, including ethics quality. In this study, we explored whether ethical leadership practices contribute to employees’ willingness to raise ethical concerns to those in the organization who have the authority to take corrective action. Methods: We conducted a secondary analysis of 2014 IntegratedEthics Staff Survey data administered to a random sample of 50% of VA health system staff. The data we used reflected responses from 42,412 employees who were associated with 141 administratively defined medical centers that encompass more than 1,400 sites of care delivery and VHA administrative program offices. The response rate to the survey was 29.4%. Results: Employees positioned higher in the organizational hierarchy were more comfortable raising ethical concerns than lower ranked employees. Ethical leadership practices, and especially those that created an expectation of trust, follow-through, and fair treatment, made it more likely that employees would raise ethical concerns with managers. Conclusion: Speaking up about ethical concerns is essential to the delivery of high-quality patient care and is enabled by managers who embody ethical leadership practices. Ethics programs can help create favorable conditions for raising ethical concerns by providing managers and supervisors with ethical leadership coaching, recognizing power differentials, and modeling more egalitarian communication practices. More research is needed to understand how employees conceptualize ethics voice and to assess the comparative effectiveness of different methods of encouraging speaking up about ethical concerns in health care organizations.
Enhancing safety of cytomegalovirus-based vaccine vectors by engaging host intrinsic immunity

Live-attenuated, spread-deficient rhesus CMV vectors retain T cell immunogenicity. Building a safer CMV vector Vaccine vectors based on cytomegalovirus (CMV) show strong T cell induction and protection against a multitude of pathogens. However, CMV can be harmful to people who are immunodeficient or immunosuppressed. Marshall et al. genetically modified rhesus CMV to allow engagement of host intrinsic immunity. The modified ΔRh110 vector did not spread once administered to nonhuman primates but still induced robust T cell immunity. Hansen et al. showed in a simian immunodeficiency virus (SIV) challenge model that the ΔRh110 vector provided equivalent protection to the parental vector, enabling control and progressive clearance of virus from more than half of the vaccinated primates. Most protected animals that were rechallenged 3 years later were able to control the second challenge, demonstrating the durability of this vaccine. Mutations in the human CMV vector should lead to a potent but restrained CMV that could be used widely in people. Rhesus cytomegalovirus (RhCMV)–based vaccines maintain effector memory T cell responses (TEM) that protect ~50% of rhesus monkeys (RMs) challenged with simian immunodeficiency virus (SIV). Because human CMV (HCMV) causes disease in immunodeficient subjects, clinical translation will depend upon attenuation strategies that reduce pathogenic potential without sacrificing CMV’s unique immunological properties. We demonstrate that “intrinsic” immunity can be used to attenuate strain 68-1 RhCMV vectors without impairment of immunogenicity. The tegument proteins pp71 and UL35 encoded by UL82 and UL35 of HCMV counteract cell-intrinsic restriction via degradation of host transcriptional repressors. When the corresponding RhCMV genes, Rh110 and Rh59, were deleted from 68-1 RhCMV (ΔRh110 and ΔRh59), we observed only a modest growth defect in vitro, but in vivo, these modified vectors manifested little to no amplification at the injection site and dissemination to distant sites, in contrast to parental 68-1 RhCMV. ΔRh110 was not shed at any time after infection and was not transmitted to naïve hosts either by close contact (mother to infant) or by leukocyte transfusion. In contrast, ΔRh59 was both shed and transmitted by leukocyte transfusion, indicating less effective attenuation than pp71 deletion. The T cell immunogenicity of ΔRh110 was essentially identical to 68-1 RhCMV with respect to magnitude, TEM phenotype, epitope targeting, and durability. Thus, pp71 deletion preserves CMV vector immunogenicity while stringently limiting vector spread, making pp71 deletion an attractive attenuation strategy for HCMV vectors.
RNA-seq Analysis of Clitea metallica (Coleoptera: Chrysomelidae), Provides Insights Into Cuticle-Related Genes and miRNAs

Abstract The citrus leaf beetle, Clitea metallica, is a specialized citrus pest through feeding on fresh leaves by larva and adults, and causes nicks and holes into leaves, leaving only a waxy surface layer. Insect cuticle is a complex exoskeleton that is not only involved in development but also protects the insect from environmental contaminations. Due to these key roles of the cuticle, cuticle-related genes are currently investigated in understanding the insect physiology in adaptation. Therefore, in this study, we built two libraries, transcriptomic (43 million clean reads) and small RNA (17 million clean reads), of C. metallica to identify cuticle-related genes and possibly associated miRNAs, being as an example to explore these data sets. Our results showed that a total of 47 cuticular protein genes were identified and most of these genes harbored a conserved motif (the Rebers and Riddiford motif) and belonged to the CPR family. Unigenes encoding proteins involved in chitin synthesis and degradation were also identified, including chitin synthase (2 unigenes), chitinase (14 unigenes), chitinase-like protein (2 unigenes), and chitin deacetylase (5 unigenes). Based on the small RNA library, we identified 30 miRNAs conserved across insect species. Among these miRNAs, 14 were predicted to be target genes associated with cuticle synthesis and degradation. In summary, 70 cuticle-related genes and 14 cuticle-related miRNAs were identified based on the transcriptome and small RNA library of C. metallica. These data sets will promote the understanding of cuticle molecular regulation in C. metallica as well as provide new potential targets for pest control.
Grain consumption and risk of gastric cancer: a meta-analysis

Abstract This study evaluated the relationship between grain consumption and the risk of gastric cancer. A total of 19 studies met the inclusion criteria. For whole grain consumption, there was a 13% reduction in the risk of gastric cancer (p = .003), and a subgroup analysis showed that a large amount of whole grain consumption reduced the risk of gastric cancer by 44% (p < .001). For refined grain consumption, there was a 36% increase in the risk of gastric cancer (p < .001); a subgroup analysis showed that a large and a moderate amount of refined grain consumption increased the risk of gastric cancer by 63% (p < .001) and 28% (p < .001), respectively. A large intake of whole grains might be protective against gastric cancer, whereas the ingestion of refined cereals may be a risk factor for gastric cancer. Moreover, the risk of cancer increases with the increase of refined grain intake.
Pembrolizumab for the treatment of head and neck squamous cell cancer

ABSTRACT Introduction: Groundbreaking progress in cancer immunotherapy in the recent years has revolutionized the field of oncology with unprecedented survival rates in multiple cancer types. Head and neck cancers comprise the sixth most common cancer type in the United States with estimated 14,620 deaths in 2019. Two checkpoint inhibitors, e.g. antibodies against programmed cell death protein 1 (PD-1), are currently FDA approved for second-line therapy of recurrent and/or metastatic head and neck squamous cell carcinomas (HNSCC). Pembrolizumab is one of the two approved anti-PD-1 antibodies and under active investigation of its role in managing HNSCCs. Areas covered: This review provides an in-depth discussion of pembrolizumab’s structural features, pharmacokinetics, pharmacodynamics, efficacy data, toxicity profile, ongoing studies, and competing agents including the standard of care options in the context of treating HNSCCs. Expert opinion: Immune checkpoint inhibitor therapy is already an integral part of HNSCC management, especially in the recurrent and/or metastatic stage, and is preferable to conventional cytotoxic therapies due to a generally more favorable toxicity profile. Pembrolizumab’s role in treating HNSCC is highly anticipated to expand over to other contexts such as definitive combination therapy and neoadjuvant therapy for locally advanced HNSCC.
Tofacitinib for the treatment of recalcitrant palmoplantar pustulosis: A case report

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