Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of a Monoclonal Antibody against Human NTCP That Blocks Hepatitis B Virus Infection

A number of entry inhibitors are being developed to enhance the treatment of HBV patients with oral nucleoside/nucleotide analogues (NA). To amplify the effectiveness of NA therapy, several efforts have been made to develop therapeutic MAbs with neutralizing activity against HBs antigens. ABSTRACT Hepatitis B virus (HBV) infects 240 million people worldwide. Current therapy profoundly suppresses HBV replication but requires long-term maintenance therapy. Therefore, there is still a medical need for an efficient HBV cure. HBV enters host cells by binding via the preS1 domain of the viral L protein to the Na+/taurocholate cotransporting polypeptide (NTCP). Thus, NTCP should be a key target for the development of anti-HBV therapeutics. Indeed, myrcludex B, a synthetic form of the myristoylated preS1 peptide, effectively reduces HBV/hepatitis D virus (HDV) infection and has been approved as Hepcludex in Europe for the treatment of patients with chronic HDV infection. We established a monoclonal antibody (MAb), N6HB426-20, that recognizes the extracellular domain of human NTCP and blocks HBV entry in vitro into human liver cells but has much less of an inhibitory effect on bile acid uptake. In vivo, administration of the N6HB426-20 MAb prevented HBV viremia for an extended period of time after HBV inoculation in a mouse model system without strongly inhibiting bile acid absorption. Among the extracellular loops (ECLs) of NTCP, regions of amino acids (aa) 84 to 87 in ECL1 and aa 157 to 165 near ECL2 of transmembrane domain 5 are critically important for HBV/HDV infection. Epitope mapping and the three-dimensional (3D) model of the NTCP structure suggested that the N6HB426-20 MAb may recognize aa 276/277 at the tip of ECL4 and interfere with binding of HBV to the region from aa 84 to 87. In summary, we identified an in vivo neutralizing NTCP-targeting antibody capable of preventing HBV infection. Further improvements in efficacy of this drug will pave the way for its clinical applications. IMPORTANCE A number of entry inhibitors are being developed to enhance the treatment of HBV patients with oral nucleoside/nucleotide analogues (NA). To amplify the effectiveness of NA therapy, several efforts have been made to develop therapeutic MAbs with neutralizing activity against HBs antigens. However, the neutralizing effect of these MAbs may be muted by a large excess of HBsAg-positive noninfectious particles in the blood of infected patients. The advantage of NTCP-targeted HBV entry inhibitors is that they remain effective regardless of viral genotype, viral mutations, and the presence of subviral particles. Although N6HB426-20 requires a higher dose than myrcludex to obtain equivalent suppression of HBV in a model mouse system, it maintained the inhibitory effect for a long time postadministration in proportion to the half-life of an IgG MAb. We believe that further improvements will make this antibody a promising treatment option for patients with chronic hepatitis B.
Tracking sentiments toward fat acceptance over a decade on Twitter

The fat acceptance (FA) movement aims to counteract weight stigma and discrimination against individuals who are overweight/obese. We developed a supervised neural network model to classify sentiment toward the FA movement in tweets and identify links between FA sentiment and various Twitter user characteristics. We collected any tweet containing either “fat acceptance” or “#fatacceptance” from 2010–2019 and obtained 48,974 unique tweets. We independently labeled 2000 of them and implemented/trained an Average stochastic gradient descent Weight-Dropped Long Short-Term Memory (AWD-LSTM) neural network that incorporates transfer learning from language modeling to automatically identify each tweet’s stance toward the FA movement. Our model achieved nearly 80% average precision and recall in classifying “supporting” and “opposing” tweets. Applying this model to the complete dataset, we observed that the majority of tweets at the beginning of the last decade supported FA, but sentiment trended downward until 2016, when support was at its lowest. Overall, public sentiment is negative across Twitter. Users who tweet more about FA or use FA-related hashtags are more supportive than general users. Our findings reveal both challenges to and strengths of the modern FA movement, with implications for those who wish to reduce societal weight stigma.
Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway

ABSTRACT Acute lung injury (ALI) is classified as a moderate or mild acute respiratory distress syndrome and is a prominent cause of morbidity and mortality among the critically ill population. Ramelteon is a melatonin receptor agonist with anti-inflammatory and antioxidant effects. The current study investigated the role of ramelteon in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs) and its potential regulatory mechanisms. A CCK-8 assay was used to examine the effect of ramelteon on the viability of LPS-induced HPMECs, HPMECs treated with ML385 [a Nrf2 inhibitor] and HPMECs treated with SnPP [a HO-1 inhibitor]. The Nrf2/HO-1 signaling pathway was additionally assessed by performing Western blotting. The levels of oxidative stress and inflammatory cytokines in HPMECs were detected using kits and reverse transcription-quantitative PCR. Cell apoptosis was evaluated via TUNEL staining. Furthermore, cell permeability was assessed using a FITC-dextran fluorescent probe, ZO-1 and occludin expression was determined via Western blotting. The results demonstrated that ramelteon elevated HPMEC viability after LPS stimulation. Additionally, ramelteon markedly reduced LPS-induced oxidative stress, inflammation and apoptosis. Moreover, cell permeability was notably decreased in ramelteon-treated groups and was accompanied by upregulated ZO-1 and occludin expression. Ramelteon treatment also activated the Nrf2/HO-1 signaling pathway in LPS-induced HPMECs. Furthermore, the addition of ML385 or SnPP reversed the protective effects of ramelteon on LPS-induced oxidative stress, inflammation, apoptosis and cell dysfunction in HPMECs. Collectively, the results suggested that ramelteon alleviated LPS-induced HPMEC damage by activating the Nrf2/HO-1 signaling pathway, making it an effective treatment for ALI.
Complete Genome Sequence of Pseudomonas sp. Strain MM213, an Isolate from a Brookside in Bielefeld, Germany

Here, we report the complete genome sequence of Pseudomonas sp. strain MM213 of the Pseudomonas mandelii group, which was isolated from a brookside in Bielefeld, Germany. The genome size is 6,746,355 bp, with a GC content of 59.4% and 6,145 predicted protein-coding sequences. ABSTRACT Here, we report the genome sequence of Pseudomonas sp. strain MM213, isolated from brookside soil in Bielefeld, Germany. The genome is complete and consists of 6,746,355 bp, with a GC content of 59.4% and 6,145 predicted protein-coding sequences. Pseudomonas sp. strain MM213 is part of the Pseudomonas mandelii group.
Validity and feasibility of a seated push-up test to indicate skeletal muscle mass in well-functioning older adults

ABSTRACT Introduction Skeletal muscle mass (SMM) is a major component of the human body (> 30% of the body-weight) and plays crucial role in many bodily functions. However, SMM assessments require a complex and costly machine, which delays the ability to detect abnormalities related to SMM decline and, subsequently, reduces the effectiveness of the clinical management of older adults. Purpose This study aimed to: 1) assess the correlation between upper limb loading during a seated push-up test (ULL-SPUT) and SMM (concurrent validity); 2) compare the SMM of participants who passed and failed a seated push-up test (SPUT; discriminant validity); and 3) explore the ability of a failed SPUT to identify older individuals with low SMM. Methods Participants (n = 40, age approximately 73 years) were cross-sectionally assessed for their SMM using a portable bioelectrical impedance analysis, and SPUTs were evaluated using digital push-up loading devices that were the size of clinical push-up boards, in three starting positions: 1) high; 2) ring, and 3) long sitting positions. Results The ULL-SPUT, especially in a ring sitting position, was significantly correlated to SMM (rs = 0.457–0.608, p < .005). The SMM and ULL-SPUT were significantly different between participants who passed and failed the SPUT (p < .05). Failure to complete the SPUT – that is, being unable to lift the body up from the floor during the test – showed an excellent ability to indicate participants with an SMM of < 28% of their body-weight (sensitivity > 83%, specificity > 82%, area under the curve = 0.93). Conclusions The inability to lift the body up from the floor during sitting using the upper limbs can be used as a screening tool to indicate those with low SMM. Such a simple screening measure may enhance the distribution of healthcare services across various community- and home-based settings, particularly during the coronavirus (COVID-19) pandemic, when hospital services are limited for many individuals, including older adults.
Circ‐Sirt1 inhibits vascular smooth muscle cells proliferation via the c‐Myc/cyclin B1 axis

Vascular smooth muscle cells (VSMCs) are an important cellular component of the vascular wall. Restenosis is mainly due to VSMC excessive proliferation. However, little is known about the role of circRNAs in VSMC proliferation and phenotypic switching. Herein, using fluorescence in situ hybridization assay and quantitative real‐time polymerase chain reaction, we found that circ‐Sirt1 was markedly downregulated in neointimal formation after injury and in VSMCs treated with platelet‐derived growth factor BB (PDGF‐BB). Bromodeoxyuridine and MTT assays confirmed the inhibitory role of circ‐Sirt1 on cell proliferation. Mechanistically, circ‐Sirt1 was mainly expressed in the cytoplasm of VSMCs. Through RNA immunoprecipitation and RNA pull‐down assays, we found that circ‐Sirt1 bound with c‐Myc, which protein associated with proliferation of VSMCs. Chromatin immunoprecipitation assay also provided evidence that the overexpression of circ‐Sirt1 almost ceased PDGF‐BB‐induced binding of c‐Myc to the promoter of cyclin B1 in VSMCs. These results indicated that circ‐Sirt1 had an inhibitory effect on c‐Myc activity, providing a mechanism for suppressing PDGF‐BB‐induced VSMC proliferation by direct interactions with c‐Myc and its sequestration in the cytoplasm. Overall, our study demonstrated that a previously unrecognized circ‐Sirt1/c‐Myc/cyclin B1 axis in VSMCs mediates neointimal formation following injury.
Three Years Survival and Factor Predicting Amputation or Mortality in Patients with High Risk for Diabetic Foot Ulcer in Fatmawati General Hospital, Jakarta

Background: Diabetic foot is one of major complication in diabetes patients with unfavorable outcome. Survival study in outpatients is limited and factors related are inconsistent. Survival and its modifiable risk factors should be identified early since the foot at risk status to reduce amputation/mortality in type 2 diabetes mellitus (T2DM). Objective: The aims of this study were to investigate survival probability for amputation or mortality, compare different ulcer risk classification, and figure out the relation of status of ulcer risk, age, gender, diabetes duration, body mass index, fasting plasma glucose, HbA1C, and LDL with amputation or mortality. Methods: This is a retrospective cohort study of 487 T2DM subjects who visited internal medicine outpatient clinic in Fatmawati General Hospital since January-December 2016. Status of ulcer risk and risk factors were extracted from medical record and lower-extremity amputation or mortality was observed in 3 years from baseline. Result: Three years overall survival is 85.7% (SE 0.17). Patients with high risk for foot ulcer have survival probability of 80.2% (SE 0.027), which is lower compared to non-high risk for foot ulcer with survival probability of 91.8% (SE 0.019). Patients with high risk for foot ulcer (aHR 2.386 [95% CI 1.356-4.20]; P = .003), aged ≥60 years old (aHR 2.051 [95% CI 1.173-3.585]; P = .012), and HbA1C ≥7% (aHR 2.022 [95% CI 1.067-3.830]; P = .031) were independently associated with amputation or mortality. Conclusion: T2DM patients with high risk for foot ulcer have lower survival probability and higher risk for amputation or mortality in 3 years compared to patients with non-high risk for foot ulcer. Status of ulcer risk, age ≥60 years, and HbA1C ≥7% were associated with amputation or mortality in 3 years observation.
Use of Palliative Care Among Commercially Insured Patients With Metastatic Cancer Between 2001 and 2016

PURPOSE: Early palliative care, concomitant with disease-directed treatments, is recommended for all patients with advanced cancer. This study assesses population-level trends in palliative care use among a large cohort of commercially insured patients with metastatic cancer, applying an expanded definition of palliative care services based on claims data. METHODS: Using nationally representative commercial insurance claims data, we identified patients with metastatic breast, colorectal, lung, bronchus, trachea, ovarian, esophageal, pancreatic, and liver cancers and melanoma between 2001 and 2016. We assessed the annual proportions of these patients who received services specified as, or indicative of, palliative care. Using Cox proportional hazard models, we assessed whether the time from diagnosis of metastatic cancer to first encounter of palliative care differed by demographic characteristics, socioeconomic factors, or region. RESULTS: In 2016, 36% of patients with very poor prognosis cancers received a service specified as, or indicative of, palliative care versus 18% of those with poor prognosis cancers. Being diagnosed in more recent years (2009-2016 v 2001-2008: hazard ratio [HR], 1.8; P < .001); a diagnosis of metastatic esophagus, liver, lung, or pancreatic cancer, or melanoma (v breast cancer, eg, esophagus HR, 1.89; P < .001); a greater number of comorbidities (American Hospital Formulary Service classes > 10 v 0: HR, 1.71; P < .001); and living in the Northeast (HR, 1.43; P < .001) or Midwest (v South: HR, 1.39; P < .001) were the strongest predictors of shorter time from diagnosis to palliative care. CONCLUSION: Use of palliative care among commercially insured patients with advanced cancers has increased since 2001. However, even with an expanded definition of services specified as, or indicative of, palliative care, < 40% of patients with advanced cancers received palliative care in 2016.
Research on the mechanisms of taraxerol for the treatment of gastric cancer effect based on network pharmacology

Background: Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. Methods: We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6. 2 software were used to analyze the protein–protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. Results: We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. Conclusion: Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.
A scoping review of therapies used to treat psychological trauma post perinatal bereavement

ABSTRACT Background Up to 39% of women who experience perinatal bereavement proceed to develop Post-Traumatic-Stress-Disorder (PTSD), with this large proportion meriting treatment. Before setting-up a treatment service for postnatal women who are experiencing psychological trauma, it is important to identify what therapies have been used in-the-past to address this problem. Aim To scope for research that has implemented therapies to treat psychological trauma post perinatal bereavement, for potential inclusion in a flexible treatment package. Method A scoping review mapped coverage, range, and type of research that has reported on prior therapies used to treat psychological trauma post perinatal bereavement. Findings Due to the dearth of papers that directly addressed perinatal bereavement, we widened the scope of the review to view what treatments had been used to treat psychological trauma post-childbirth. Out of 23 studies that report on effectiveness of therapies used to treat psychological trauma post-childbirth, only 4-focused upon treating PTSD post perinatal bereavement (3 effective/1 ineffective). Successful treatments were reported by Kersting et al. (2013), who found CBT effective at reducing PTSD symptoms post-miscarriage, termination for medical reasons, and stillbirth (n = 33 & n = 115), and Navidian et al. (2s017)) found that 4-sessions of grief-counselling reduced trauma symptoms post-stillbirth in (n = 50) women. One study by Huberty et al. (2020found on-line yoga to be ineffective at reducing PTSD symptoms post-stillbirth. Conclusions A dearth of research has explored effectiveness of therapies for treating psychological trauma post perinatal bereavement and post-childbirth, with need to develop and test a research informed flexible counselling package.
Insulin sensitivity in the aged heart is improved by down-regulation of KAT7 in vivo and in vitro

ABSTRACT Insulin has an important regulatory effect on the heart, and the important regulatory effect of insulin on the heart is the regulation of substrate utilization. Studies have shown that aging is closely related to insulin resistance, and aging is thought to be one of the underlying causes of insulin resistance. Additionally, chronic inflammation is a major risk factor for aging and aging-related diseases. How to delay or reverse insulin resistance caused by aging is an important scientific problem. In the current study, we used cardiomyocyte cell lines and isolated heart cells as an in vitro model, and aged mice as in vivo model to study the effect of KAT7 on insulin resistance, and results showed that knockdown or inhibiting KAT7 can significantly increase the insulin sensitivity in vivo and in vitro. In addition, the knockdown of KAT7 could reduce inflammation and oxidative stress caused by aging. These findings indicate that KAT7 can be used as one of the potential targets for the treatment of insulin resistance caused by aging.
Second primary malignancy risk after Hodgkin lymphoma treatment among HIV-uninfected and HIV-infected survivors

Abstract We compared secondary primary malignancy risk (SPM) in HIV-uninfected and HIV-infected Hodgkin lymphoma (HL) survivors. We used data from the California Cancer Registry on patients diagnosed with HL from 1990 to 2015 (all ages included), and standardized incidence ratios (SIRs) and multivariable competing risk models for analyses. Of 19,667 survivors, 735 were HIV-infected. Compared with the general population, the risk of SPM was increased by 2.66-fold in HIV-infected and 1.92-fold in HIV-uninfected survivors. Among HIV-infected survivors, median time to development of SPM was shorter (5.4 years) than in HIV-uninfected patients (8.1 years). Additionally, the highest risk of SPM was observed <2 years after diagnosis in HIV-infected survivors (SIR = 4.47), whereas risk was highest ≥20 years after diagnosis (SIR = 2.39) in HIV-uninfected survivors. The risk of SPMs persisted for decades and was higher among HIV-infected survivors, suggesting that these patients should benefit from long-term surveillance and cancer prevention practices.
Women in public relations: ascribed and avowed leadership identities and expectations

ABSTRACT Women who aspire to leadership positions in public relations have to develop political astuteness when it comes to addressing ascribed identities and expectations associated with gender and race. Through 51 in-depth interviews with women working in mid-management and senior-executive level positions in public relations in the U.S., this study provides new insights into women’s perceptions regarding the necessary knowledge, skills and abilities to succeed in public relations leadership. The study revealed some women’s preferences for contemporary management styles such as servant leadership and transformational leadership as well as barriers to advancement and influence, particularly for women of color.
Mapping the Benefits from Innovation Contests

Overview: An innovation contest is an effective way to address an organization’s technical needs. With its pay-for-success and winner(s)-take-all format, organizations have received novel and high-quality solutions to their problems at lower costs than solving them internally. These successes have driven researchers to focus on strategies that further enhance the resulting solutions. This narrow focus, however, might ignore benefits that are also important to these organizations. Our work leverages an in-depth case study of NASA’s highly successful 3D Printed Habitat Challenge; we analyzed how it benefited the relevant NASA subject matter experts. Our resulting framework characterizes the range, and sources, of potential benefits across different stages of an innovation contest, some of which we found to be more valuable than the solutions. These findings emphasize the need to broaden the existing focus on solutions and highlight new opportunities for practitioners to address their needs through innovation contests.
Orpheus’ Head at the Mouth of the Meles: Conon Narratives 45

Most of Conon’s Narratives is only available as abridged by Photius in the Bibliotheca, but epitomization has introduced many obscurities into Conon’s often-idiosyncratic stories. This paper examines one such obscurity in Conon’s Orpheus narrative (45), namely, his decapitated head’s discovery by the mouth of one Meles River—a unique mythological variant. Against scholarly uncertainty, this river can be confidently identified with the Smyrnean Meles, which connects meaningfully with the Orpheus myth both via its Homeric associations and by means of etymological wordplay. These interconnections testify to a level of literary sophistication in the Narratives that abridgment has tended to conceal.