Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease progression as occurs in humans. Pet dogs can be leveraged for the exploration of novel therapies that exploit tumor cell vulnerabilities, perturb local microenvironmental cues, and amplify immunologic recognition. In this capacity, pet dogs can serve as valuable corroborative models for realizing the science and best clinical practices necessary for understanding and combating osteosarcoma metastases.
Imipramine and Venlafaxine Differentially Affect Primary Glial Cultures of Prenatally Stressed Rats

Here, we examine the effects of prenatal administration of two antidepressants—imipramine (IMI) and venlafaxine (VEN)—on morphology and activity of a primary glial culture. Microglia are targeted by antidepressants used for antenatal depression and are important regulators of central nervous system development. In this study, female Wistar rats were assigned to one of four groups: a control group that received water ad libitum (1), and groups that received additionally once daily either water (2), IMI (10 mg/kg) (3), or VEN (20 mg/kg) (4) by oral gavage from gestation day 7 to 22. Oral gavage administration induced prenatal stress. Cell cultures were obtained from the brains of 1-day-old pups. Prenatal stress caused a disturbance of sensorimotor function in pups. Prenatal stress also produced alterations in the glial cultures, specifically, an increased percentage of microglia in the mixed glial cultures and an increased percentage of dead cells. Moreover, increased levels of IL1-β, TNF-α, NO, and an increased expression of CX3CR1 mRNA were found in microglia. However, the ratio of Bax/Bcl2 mRNA was reduced. Prenatal stress increased the vulnerability of microglia to lipopolysaccharide (LPS). The mixed glial culture derived from pups exposed to IMI showed greater morphological changes and the highest percentage of microglia. Microglia were characterized by the largest increase in the production of pro-inflammatory cytokines and NO, and the greatest reduction in the expression of CX3CR1 mRNA. Exposure to IMI reduced the effects of LPS on IL-1β production and Bax/Bcl2 mRNA, and exacerbated the effects of LPS on CX3CR1 mRNA expression. Prenatal administration of VEN induced protective effects on microglia, as measured by all studied parameters. Taken together, our data suggest that, by disturbing microglia function, exposure to even mild forms of chronic prenatal stress may predispose individuals to psychiatric or neurodevelopmental disorders. These data also indicate that chronic mild stress sensitizes microglia to immune challenges, which may lead to enhanced neuronal damage in the embryonic brain. The observed detrimental effects of IMI on microglial activity under conditions of prenatal stress may help to explain the teratogenic effects of IMI reported in the literature.
Two new species of the similis-subgroup of Triconia Böttger-Schnack, 1999 (Copepoda, Oncaeidae) and a redescription of T. denticula Wi, Shin & Soh, 2011 from the northeastern equatorial Pacific

ABSTRACT Three species of the similis-subgroup of the genus Triconia Böttger-Schnack, 1999 in the family Oncaeidae Giesbrecht, 1893 [“1892”] are described based on specimens collected by using a fine mesh net in the northeastern equatorial Pacific Ocean. One species is newly recorded in the equatorial Pacific, and the other two species are new to science. Triconia komo n. sp. is closely related to T. hawii (Böttger-Schnack & Boxshall, 1990), but differs distinctly in the relative length of the outer basal seta on P5 in the female as well as slightly in the relative length of the seta VI on caudal ramus in both sexes. Triconia onnuri n. sp. closely resembles T. similis (Sars, 1918), but females can be distinguished by the relative length of the outer exopodal seta and the outer basal seta on P5. Both sexes differ from T. similis in the relative lengths of endopodal spines on swimming legs 3 and 4 as well as in the form of caudal seta VI. The female of Triconia denticula Wi, Shin & Soh, 2011, which is newly recorded in the equatorial Pacific, is redescribed including morphological details and differences compared to the original description from Korean waters. The type material of T. denticula deposited in the National Institute of Biological Resources, Incheon (NIBR) was re-examined and found to be inconclusive for taxonomic purposes because the deposited copepod material and its labelling does not correspond to the description of the species. A fundamental revision of the type material of T. denticula is required. The present account includes an indication of the intraspecific variation in the endopodal spine lengths on swimming legs 2 to 4 for all three species, which is essential for assessing the usefulness of these characters for unequivocal identification of Triconia species. The spine lengths on exopodal segments 1 and 2 on swimming legs 3 and 4 are proposed as new morphometric characters for the identification of males of Triconia species, which are otherwise very similar in morphology.
Engineered symbionts activate honey bee immunity and limit pathogens

Inducing immune bee genes Honey bees are prone to parasitism by the Varroa mite, which is a vector for several bee pathogens. However, honey bees are also host to the symbiotic gut bacterium Snodgrassella alvi. Leonard et al. engineered S. alvi to produce double-stranded RNA (dsRNA)—a stimulus for insect RNA interference defense responses—from a plasmid containing two inverted promoters tagged with a fluorescent label (see the Perspective by Paxton). This dsRNA module can be targeted to interfere with specific bee genes as well as crucial viral and mite genes. The authors found that gene expression could be blocked for at least 15 days as the symbionts established in the bees' guts and continuously expressed the dsRNA constructs. S. alvi with specifically targeted plasmids not only suppressed infection with deformed wing virus but also effectively reduced Varroa mite survival. Science, this issue p. 573; see also p. 504 Engineered gut bacteria induce immune responses to control honey bee gene expression and protect bees against pathogens and parasites. Honey bees are essential pollinators threatened by colony losses linked to the spread of parasites and pathogens. Here, we report a new approach for manipulating bee gene expression and protecting bee health. We engineered a symbiotic bee gut bacterium, Snodgrassella alvi, to induce eukaryotic RNA interference (RNAi) immune responses. We show that engineered S. alvi can stably recolonize bees and produce double-stranded RNA to activate RNAi and repress host gene expression, thereby altering bee physiology, behavior, and growth. We used this approach to improve bee survival after a viral challenge, and we show that engineered S. alvi can kill parasitic Varroa mites by triggering the mite RNAi response. This symbiont-mediated RNAi approach is a tool for studying bee functional genomics and potentially for safeguarding bee health.
Seeking Divine Intervention to Manage the Advanced Stages of Breast Cancer in Southwestern Nigeria.

BACKGROUND The World Health Organization records indicate that breast cancer is the most common cancer in women both in developed and developing regions of the world. In developed countries, breast cancer is the second cause of cancer-related deaths, whereas in developing countries, breast cancer is the leading cause of cancer-related mortality in women. The empirical literature on Nigeria indicates that women present with advanced stages of the illness. OBJECTIVES To explore the health-seeking behaviors of Southwestern Nigerian women with advanced breast cancer from the time they noticed a breast abnormality to their eventual presentation at the hospital for the management of the illness. METHODS Thirty women with advanced stages of breast cancer in a large tertiary, referral, teaching, and university-affiliated Southwestern Nigeria Hospital were purposively selected for study participation. Participants completed a demographic information form and an in-depth face-to-face, one-on-one, semistructured interview guided by open-ended questions. Data analysis was inductive. RESULTS Findings revealed that women sought divine interventions for the management of breast cancer. Prayer and spirituality were associated with high levels of optimism among the study participants. CONCLUSION Nurses should provide information and counseling to women and the general public on the etiology and appropriate management of breast abnormalities and include the importance of a spiritual dimension of care. IMPLICATIONS FOR PRACTICE Findings indicate the need to introduce a spiritual dimension to the care of women with advanced breast cancer. Findings also indicate the need for a comprehensive population-based breast health education.
A qualitative investigation of models of community mental health care for women with perinatal mental health problems

Abstract Background Specialist community perinatal mental health teams support women diagnosed with moderate to severe psychiatric difficulties in pregnancy or postnatally. These teams are being expanded across the UK, and there is considerable international interest in this model of care. However, not all women access these teams, and many are instead supported by community mental health services that do not specialise in the perinatal period. Aims To explore perinatal women’s experiences of specialist perinatal versus generic non-perinatal community mental health support. Methods Semi-structured interviews were conducted with 36 women diagnosed with perinatal mental health difficulties who were supported in the community either by a specialist perinatal or general non-perinatal mental health service. Data were analysed thematically. Results Women felt that specialist perinatal and non-perinatal services alike were under-resourced and somewhat too narrow in their remit, but reported positive experiences across both settings. They particularly valued the specialist expertise offered by perinatal teams, but also valued greater continuity of care over a longer period, which some non-perinatal teams provided. Conclusions The findings suggest that women who experience perinatal mental health difficulties value specialist perinatal expertise, but that general, non-perinatal teams may also have advantages for some. Further research into optimal care arrangements is merited.
Tripterygium wilfordii multiglycosides combined with prednisone in the treatment of idiopathic membranous nephropathy

Abstract Aim: The aim of this review is to assess the efficacy and safety of tripterygium wilfordii multiglycosides combined with prednisone in the treatment of idiopathic membranous nephropathy. Background: Tripterygium wilfordii multiglycosides, a Chinese patent medicine, is widely in-depth research in China, and is proved to have anti-inflammatory and immunosuppressive effect. It has been extensively used in China for the treatment of autoimmune diseases, such as idiopathic membranous nephropathy (IMN). However, there has no relevant systematic review studied on its effects and safety been reported. We plan to perform a systematically reviewing to assess the efficacy and safety of tripterygium wilfordii multiglycosides combined with hormones in the treatment of IMN. Methods: Seven electronic databases will be searched to identify eligible trials. Randomized controlled trials (RCTs) that compared tripterygium wilfordii multiglycosides combined with prednisone versus standard therapy are included. Methodological quality is assessed using the Cochrane Collaboration Risk of Bias tool. A random- or fixed-effect model is used to analyze outcomes that are expressed as risk ratios (RRs) or mean differences (MD), and the I2 statistic is used to assess heterogeneity. Results: A high-quality synthesis of current evidence of tripterygium wilfordii multiglycosides combined with prednisone in the treatment of idiopathic membranous nephropathy will be provided in this study. Conclusion: This systematic review will provide evidence of whether tripterygium wilfordii multiglycosides is an effective intervention for idiopathic membranous nephropathy. PROSPERO registration number: No.CRD42018118179.
Effects of traditional Chinese exercise on lumbar disc herniation

Abstract Background: A large number of randomized controlled trials (RCTs) have shown that traditional Chinese exercises (TCE) have certain advantages in the treatment of lumbar disc herniation (LDH). However, due to the diversity of TCE methods, their relative effectiveness has not been studied and explained. Therefore, based on the network meta-analysis (NMA), this study will compare the differences in the effectiveness of TCE methods in the treatment of LDH, in order to provide a reference for clinical treatment. Methods: We will search PubMed, MEDLINE, Embase, the Cochrane Library, China National Knowledge Infrastructure (CHKD-CNKI), WANFANG database (Chinese Medicine Premier), Chinese Biomedical Literature database VIP for relevant RCTs of ACU treatments for POP, from their inceptions to March 18, 2019. STATA 15.0 and GEMTC software will be used to perform a NMA. The evidence will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation approach and the type 1 error rate will be assessed by trial sequential analysis. Results: The results of this review will be submitted to a recognized journal for publication. Conclusion: This proposed systematic review will evaluate the different advantages of various types of TCE in the treatment of LDH.
Soluble ST2 is associated with increased carotid intima-media thickness in patients with type 2 diabetes mellitus

Abstract Soluble suppression of tumorigenicity 2 (sST2) is a free form of membrane-bound ST2, which is a member of the interleukin-1 receptor family. Previous research has shown that sST2 is associated with diabetes, but cardiovascular risk factors have not been established. To analyze the relationship between sST2 and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). After screening, a total of 118 subjects with T2DM were divided into 2 groups according to the measurement of CIMT (normal CIMT (NCIMT), n = 58; abnormal CIMT (ACIMT), n = 60), and 60 healthy subjects (normal control (NC), n = 60) were recruited in this study. CIMT was measured by a color Doppler ultrasound, and sST2 and other metabolic parameters were measured as well. The median concentration of sST2 was elevated in the ACIMT group (31.30 ng/ml) compared with the NCIMT group (28.29 ng/ml, P < .01) and the NC group (20.15 ng/ml, P < .01). After adjustment for age and sex, log sST2 was strongly associated with smoking history (β = 0.197, 95% CI, 0.084–0.311, P < .01), FPG level (β = 0.302, 95% CI, 0.162–0.442, P < .01) and HbA1c level (β = 0.296, 95% CI, 0.165–0.426, P < .01) and negatively correlated with HDL level (β = −0.153, 95% CI, −0.259 to −0.046, P < .01). Furthermore, sST2 level was a risk factor for increased CIMT in patients with T2DM. Increased sST2 level not only was associated with indicators of glucose and lipid metabolism but also was a risk factor for increased CIMT in patients with T2DM. Thus, sST2 may be a potential novel marker to assess the progression of diabetic macrovascular complications.
Detection of type2 biomarkers for response in COPD

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease. It is important to identify patients who would respond to anti-inflammatory treatment. This prospective study aims to determine how inflammatory biomarkers could be used to predict the potential effect of inhaled corticosteroids (ICS) in terms of symptoms and lung function. We evaluated the levels of blood eosinophils, exhaled nitric oxide fraction at a flow rate of 50 ml s−1 (FeNO), alveolar nitric oxide concentration (Calv), immunoglobulin E and atopy in 43 patients with symptomatic COPD and correlated these expression levels with the changes in the COPD Assessment Test (CAT) and lung function by 12 weeks of add-on therapy with ciclesonide 400 μg d−1 on bronchodilators. The mean changes in the CAT score and FEV1 were −1.4 points and +90 ml, respectively, with significant variation in the levels of change. The area under the receiver’s operating characteristic curve (AUC) for FeNO in predicting improvements in both the CAT score and FEV1 was 0.92. The AUC for Calv and blood eosinophils was 0.82 and 0.65. Two cutoffs were chosen, one corresponding to a high value of FeNO associated with certainty for response inclusion (FeNO = 35 ppb; sensitivity = 0.67, specificity = 0.94; positive predictive value = 0.80) and the other with certainty for response exclusion (FeNO = 20 ppb; sensitivity = 1.00, specificity = 0.58, negative predictive value = 1.00). Baseline FeNO values were significantly correlated with changes in FEV1 and CAT (all p < 0.0001). FeNO could be a valuable biomarker for identifying individuals who respond to steroid therapy among patients with symptomatic COPD in terms of symptoms and airflow limitation. The study was prospectively registered with the University Hospital Medical Information Network (UMIN) in Japan (protocol ID 000010711).
Anatomically‐based transoral surgical approach to early‐stage oral tongue squamous cell carcinoma

The mainstream of treatment of early‐stage oral tongue squamous cell carcinoma (OTSCC) is represented by transoral resection with “adequate” free margins. Despite that, a precise and shared definition of “adequate margin” is lacking, and so is a standardized transoral surgical technique.The tongue is a symmetrically paired organ, consisting of intertwining intrinsic and extrinsic muscles, which can be distinguished during dissection. Routes of tumoral spread in oral tongue cancer are well‐known and should be taken into account during resection. We propose herein a standardized and replicable surgical technique to resect early‐stage OTSCC, based on rational anatomical considerations.
Structural basis of second-generation HIV integrase inhibitor action and viral resistance

Strengths and weaknesses of an HIV drug Retroviruses replicate by inserting a copy of their RNA, which has been reverse transcribed into DNA, into the host genome. This process involves the intasome, a nucleoprotein complex comprising copies of the viral integrase bound at the ends of the viral DNA. HIV integrase strand-transfer inhibitors (INSTIs) stop HIV from replicating by blocking the viral integrase and are widely used in HIV treatment. Cook et al. describe structures of second-generation inhibitors bound to the simian immunodeficiency virus (SIV) intasome and to an intasome with integrase mutations known to cause drug resistance. Passos et al. describe the structures of the HIV intasome bound to a second-generation inhibitor and to developmental compounds that are promising drug leads. These structures show how mutations can cause subtle changes in the active site that affect drug binding, show the basis for the higher activity of later-generation inhibitors, and may guide development of better drugs. Science, this issue p. 806, p. 810 Single-particle cryo–electron microscopy shows how inhibitors that bind the intasome may allow the development of better drugs against HIV. Although second-generation HIV integrase strand-transfer inhibitors (INSTIs) are prescribed throughout the world, the mechanistic basis for the superiority of these drugs is poorly understood. We used single-particle cryo–electron microscopy to visualize the mode of action of the advanced INSTIs dolutegravir and bictegravir at near-atomic resolution. Glutamine-148→histidine (Q148H) and glycine-140→serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations. Our results reveal that binding to magnesium ions underpins a fundamental weakness of the INSTI pharmacophore that is exploited by the virus to engender resistance and provide a structural framework for the development of this class of anti-HIV/AIDS therapeutics.
Genome Sequence of Salarchaeum sp. Strain JOR-1, an Extremely Halophilic Archaeon from the Dead Sea

An extremely halophilic archaeon, Salarchaeum sp. strain JOR-1, was isolated from the east coast of the Dead Sea, Kingdom of Jordan, and sequenced using single-molecule real-time (SMRT) sequencing. The GC-rich 2.5-Mbp genome was composed of a circular chromosome and a megaplasmid. The genome contained 2,633 genes and was incorporated into HaloWeb (https://halo.umbc.edu/). ABSTRACT An extremely halophilic archaeon, Salarchaeum sp. strain JOR-1, was isolated from the east coast of the Dead Sea, Kingdom of Jordan, and sequenced using single-molecule real-time (SMRT) sequencing. The GC-rich 2.5-Mbp genome was composed of a circular chromosome and a megaplasmid. The genome contained 2,633 genes and was incorporated into HaloWeb (https://halo.umbc.edu/).