Miracle-dz/UniFAR-FTUs huggingface dataset:
Accessibility and Quality of Online Cancer-Related Clinical Trial Information for Naïve Searchers

Although the Internet may help to increase cancer patients' awareness of clinical trials, little is known about the accessibility and quality of online clinical trial information. We simulated the experience of a naïve cancer patient without clinical trial knowledge by searching three popular search engines for treatment information for breast, lung, and prostate cancer, and myelodysplastic syndromes (MDS). Two coders independently evaluated website content for accessibility and quality. We screened 120 websites and identified 40 unique sites for analysis. Overall, 85% [95% confidence interval (CI), 70%–94%] of sites mentioned clinical trials on the landing page and 68% (51%–81%) included links to specific trials. Overall readability was poor. Approximately half of websites (36%–68%) included information on the potential benefits and risks of clinical trials and 40% provided information about when the site had been updated (25%–57%). Among sites with links to specific clinical trials, only 44% (25%–65%) provided an interactive interface that would allow patients to customize search results; breast (100%) and prostate (50%) sites were more interactive than lung (25%) and MDS (14%; P = 0.007). Although cancer clinical trial information is widely available on the Internet, its quality is highly variable. Given the fact that many emerging cancer therapeutics are personalized based on disease or genomic characteristics, interactive web-based interfaces could serve as powerful vehicles to help patients locate appropriate clinical trials. Without enhanced efforts to ensure greater interactivity of cancer treatment websites, patient awareness of relevant clinical trials may remain low. Cancer Epidemiol Biomarkers Prev; 24(10); 1629–31. ©2015 AACR.
From Human Cytogenetics to Human Chromosomics

Background: The concept of “chromosomics” was introduced by Prof. Uwe Claussen in 2005. Herein, the growing insights into human chromosome structure finally lead to a “chromosomic view” of the three-dimensional constitution and plasticity of genes in interphase nuclei are discussed. This review is dedicated to the memory of Prof. Uwe Claussen (30 April 1945–20 July 2008). Recent findings: Chromosomics is the study of chromosomes, their three-dimensional positioning in the interphase nucleus, the consequences from plasticity of chromosomal subregions and gene interactions, the influence of chromatin-modification-mediated events on cells, and even individuals, evolution, and disease. Progress achieved in recent years is summarized, including the detection of chromosome-chromosome-interactions which, if damaged, lead to malfunction and disease. However, chromosomics in the Human Genetics field is not progressing presently, as research interest has shifted from single cell to high throughput, genomic approaches. Conclusion: Chromosomics and its impact were predicted correctly in 2005 by Prof. Claussen. Although some progress was achieved, present reconsiderations of the role of the chromosome and the single cell in Human Genetic research are urgently necessary.
Structural Basis of CO2 Adsorption in a Flexible Metal-Organic Framework Material

This paper reports on the structural basis of CO2 adsorption in a representative model of flexible metal-organic framework (MOF) material, Ni(1,2-bis(4-pyridyl)ethylene)[Ni(CN)4] (NiBpene or PICNIC-60). NiBpene exhibits a CO2 sorption isotherm with characteristic hysteresis and features on the desorption branch that can be associated with discrete structural changes. Various gas adsorption effects on the structure are demonstrated for CO2 with respect to N2, CH4 and H2 under static and flowing gas pressure conditions. For this complex material, a combination of crystal structure determination and density functional theory (DFT) is needed to make any real progress in explaining the observed structural transitions during adsorption/desorption. Possible enhancements of CO2 gas adsorption under supercritical pressure conditions are considered, together with the implications for future exploitation. In situ operando small-angle neutron and X-ray scattering, neutron diffraction and X-ray diffraction under relevant gas pressure and flow conditions are discussed with respect to previous studies, including ex situ, a priori single-crystal X-ray diffraction structure determination. The results show how this flexible MOF material responds structurally during CO2 adsorption; single or dual gas flow results for structural change remain similar to the static (Sieverts) adsorption case, and supercritical CO2 adsorption results in enhanced gas uptake. Insights are drawn for this representative flexible MOF with implications for future flexible MOF sorbent design.
Comment on Li et al. Visual Inspection of Chromatograms Assists Interpretation of HbA1c: A Case Report. Diabetes Care 2018;41:1829–1830

We thank Li et al. (1) for their interest in our case report (2), which emphasized the value of visual inspection of chromatograms in clinical practice to assist interpretation of HbA1c. For consistency and comparability with the first and only available report, by Wajcman et al. in 1992 (3), we presented the identified mutation as c.242T>A, p.Leu81His (rs33936967), without including the translational initiation codon in variant sequence numbering. According to the latest nomenclature recommendations of the Human Genome Variation Society in 2007 (4), starting with number 1 at the A of the ATG for nucleotides and at the methionine encoded by the …
Interaction of biologic therapy with apical periodontitis and periodontitis: a systematic review.

Biologic medications (BMs) are increasingly used for the management of systemic chronic inflammatory diseases. These diseases are often associated with a higher prevalence of apical periodontitis (AP) and periodontitis (P). The purpose of this systematic review was to ascertain the interactions between AP and/or P and BMs. The review was registered in the PROSPERO database (CRD42017054756). Electronic searches were performed on Pubmed Medline, Scopus and The Web of Science from their inception through to 20 March 2018. The references of the articles selected were checked. The keywords were chosen based on a pilot search, which aimed to find the most frequently prescribed BMs. The included studies were appraised qualitatively using appropriate tools. Thirty-five articles met the inclusion criteria, comprising 16 non-randomized clinical studies, 12 in vivo animal studies and 7 case reports. Quality of information was assessed as high in 18 articles, moderate in 16 articles and low in 1 article. BMs in patients suffering from chronic inflammatory diseases seems to inhibit the progression of AP and P, and to enhance the healing response to periodontal and endodontic treatment. A healthier condition of the periodontal tissues seems to be associated with a better response of the patient to BMs therapy.
Multiorgan involvement by amyloid light chain amyloidosis

Amyloid light chain (AL) amyloidosis is a protein conformational disease. AL amyloidosis results from aggregation of misfolded proteins that are deposited in tissues as amyloid fibrils. Diagnosis of AL amyloidosis can be challenging due to its low incidence and clinical complexity. Therapy requires a risk-adapted approach involving dose reductions and schedule modifications of chemotherapy regimens along with close monitoring of hematologic and organ responses. We herein describe a patient whose condition was diagnosed as systemic AL amyloidosis and presented with splenic rupture as the initial symptom. Congo red staining of the kidney biopsy was positive. The normal structure of the liver and spleen had been replaced by amyloid deposition. The chemotherapy strategy involved a combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone.
AMG 595, an Anti-EGFRvIII Antibody–Drug Conjugate, Induces Potent Antitumor Activity against EGFRvIII-Expressing Glioblastoma

Epidermal growth factor receptor variant III (EGFRvIII) is a cancer-specific deletion mutant observed in approximately 25% to 50% of glioblastoma multiforme (GBM) patients. An antibody drug conjugate, AMG 595, composed of the maytansinoid DM1 attached to a highly selective anti-EGFRvIII antibody via a noncleavable linker, was developed to treat EGFRvIII-positive GBM patients. AMG 595 binds to the cell surface and internalizes into the endo-lysosomal pathway of EGFRvIII-expressing cells. Incubation of AMG 595 with U251 cells expressing EGFRvIII led to potent growth inhibition. AMG 595 treatment induced significant tumor mitotic arrest, as measured by phospho-histone H3, in GBM subcutaneous xenografts expressing EGFRvIII. A single intravenous injection of AMG 595 at 17 mg/kg (250 μg DM1/kg) generated complete tumor regression in the U251vIII subcutaneous xenograft model. AMG 595 mediated tumor regression in the D317 subcutaneous xenograft model that endogenously expresses EGFRvIII. Finally, AMG 595 treatment inhibited the growth of D317 xenografts orthotopically implanted into the brain as determined by magnetic resonance imaging. These results demonstrate that AMG 595 is a promising candidate to evaluate in EGFRvIII-expressing GBM patients. Mol Cancer Ther; 14(7); 1614–24. ©2015 AACR.
First report of substituted 2H-pyranoids from brown seaweed Turbinaria conoides with antioxidant and anti-inflammatory activities

Abstract The organic extract of Turbinaria conoides, a brown seaweed harvested from the Gulf of Manner region of Indian peninsular was chromatographically fractionated to yield three substituted 2H-pyranoids, namely methyl-21-yl-[5′, 6′- dihydro-5′-yl-{54-(4-hydroxybenzoyl)-oxy-(52-methylbutyl)}-3′-methyl-2H-pyran]-21-methyl butanoate (1), 11-[(3′, 6′-dihydro-4′-methyl-2′-oxo-2H-pyran-3′-yl)methyl]-10-methylhexyl benzoate (2), and [6-ethyl-3,4-dimethyl-(tetrahydro-2′, 2′, 6′-trimethyl-2H-pyran-3′-yl)-2,5-cycloheptadiene]-1-propanoate (3). The compounds 1 and 2 bearing 2H-pyranyl-4-hydroxybenzoyl and 2H-pyranyl-10-methylhexylbenzoate moieties exhibited potential antioxidant activities (IC50 0.54-0.69 mg mL−1) as commercial antioxidant (α-tocopherol IC50 0.63-0.73 mg mL−1). Likewise, potential bioactivity of the 2H-pyran derivative, 1 against 5-lipoxygenase (IC50 ∼ 1 mg mL−1) along with higher index of selectivity (COX-1 inhibitoryIC50/COX-2 inhibitoryIC50 1.88) indicated their selective anti-inflammatory properties against inducible inflammatory mediators than that displayed by commercially available non-steroidal anti-inflammatory drug (ibuprofen, 0.44). Structure activity relationship analysis of the studied compounds showed that the antioxidative and anti-inflammatory properties were directly proportional to their electronic properties. The previously undescribed 2H-pyranoids might constitute as potential antioxidative and anti-inflammatory pharmacophores for medicinal applications.
Inpatient and Emergent Resource Use of Patients on Dialysis at an Academic Medical Center

Background/Aim: End-stage renal disease patients require resources for emergent and inpatient care in addition to ambulatory dialysis. There are two dialysis modalities and settings which patients switch between. Our aim was to characterize the patterns and reasons for switching, as well as the emergent and inpatient utilization of these patients at the University Health Network. Methods: Patients who received chronic dialysis between March 1, 2006, and April 30, 2011, were identified. Utilization was measured by emergency department (ED) visits, inpatient hospitalizations, and bed-days occupied per year. Results: Out of 576 patients identified, 18.6% switched modality and/or setting. The majority of switches occurred during the first year of dialysis. Patients who switched had increased utilization compared to those on a continuous modality/setting. Overall, patients had a median rate of 0.91 ED visits per patient-year, compared to 1.56 for patients who switched modality and setting. Median inpatient bed resource requirement was 4.46 bed-days/patient-year overall, compared to 8.91 for patients who switched modality and setting. Conclusions: Emergent and inpatient utilization is related to the setting and modality of dialysis, although differences are partly explained by comorbidities. Patients who switch modalities use more resources and may be a prime population for interventions.
The Molecular Basis of Freshwater Adaptation in Prawns: Insights from Comparative Transcriptomics of Three Macrobrachium Species

Abstract Elucidating the molecular basis of adaptation to different environmental conditions is important because adaptive ability of a species can shape its distribution, influence speciation, and also drive a variety of evolutionary processes. For crustaceans, colonization of freshwater habitats has significantly impacted diversity, but the molecular basis of this process is poorly understood. In the current study, we examined three prawn species from the genus Macrobrachium (M. australiense, M. tolmerum, and M. novaehollandiae) to better understand the molecular basis of freshwater adaptation using a comparative transcriptomics approach. Each of these species naturally inhabit environments with different salinity levels; here, we exposed them to the same experimental salinity conditions (0‰ and 15‰), to compare expression patterns of candidate genes that previously have been shown to influence phenotypic traits associated with freshwater adaptation (e.g., genes associated with osmoregulation). Differential gene expression analysis revealed 876, 861, and 925 differentially expressed transcripts under the two salinities for M. australiense, M. tolmerum, and M. novaehollandiae, respectively. Of these, 16 were found to be unannotated novel transcripts and may be taxonomically restricted or orphan genes. Functional enrichment and molecular pathway mapping revealed 13 functionally enriched categories and 11 enriched molecular pathways that were common to the three Macrobrachium species. Pattern of selection analysis revealed 26 genes with signatures of positive selection among pairwise species comparisons. Overall, our results indicate that the same key genes and similar molecular pathways are likely to be involved with freshwater adaptation widely across this decapod group; with nonoverlapping sets of genes showing differential expression (mainly osmoregulatory genes) and signatures of positive selection (genes involved with different life history traits).
Combating breast cancer using combination therapy with 3 phytochemicals: Piperine, sulforaphane, and thymoquinone

Despite the significant advances in screening methods for early diagnosis, breast cancer remains a global threat and continues to be the leading cancer diagnosed in women, requiring effective therapy. Currently, combination therapy has become the hallmark of breast cancer treatment due to the high incidence of tumor recurrence and disease progression after monotherapeutic treatments, including surgery, radiotherapy, endocrine therapy, and chemotherapy. Over the past decades, there has been considerable interest in studying the anticancer effect of bioactive phytochemicals from medicinal plants combined with these conventional therapies. The rationale for this type of therapy is to use combinations of drugs that work by different mechanisms, thereby decreasing the likelihood that cancer cells will develop resistance, and also reduce the therapeutic dose and toxicity of single treatments. Three agents have received great attention with regard to their anticancer properties: 1) piperine, a dietary phytochemical isolated from black pepper (Piper nigrum L.) and long pepper (Piper longum L.); 2) sulforaphane, an isothiocyanate mainly derived from cruciferous vegetables; and 3) thymoquinone, the active compound from black seed (Nigella sativa L.). This review focused on the combined effect of these 3 compounds on conventional cancer therapy with the objective of observing enhanced efficacy compared with single treatments. This review also highlights the importance of the nanoformulation of such bioactive phytochemicals that could enhance their bioavailability by providing an efficient targeted delivery system with a reduced systemic dose while resulting in a more efficient dosing at the target site.
Clinical trial on tinnitus patients with normal to mild hearing loss: broad band noise and mixed pure tones sound therapy

Abstract Background: Tinnitus treatments present a quandary for clinicians, but no thoroughly satisfactory medical treatments are offered to tinnitus patients. Objective: We compared sound therapy effects of the broad band noise (BBN) and the mixed pure tones on tinnitus patients with normal to mild hearing loss, and the possible mechanisms were discussed. Material and methods: This study was a double-blinded randomized controlled trial. The patients in two groups were followed up for three months. We used a BBN in group A, and mixed pure tones of nine different frequencies in group B. The Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS) measuring were used to evaluate the handicap, loudness and anxiety of tinnitus. Results: The THI, VAS scores of group B after 3 months were lower than those at baseline. The VAS scores of group B were lower than those of group A at 8 and 12 weeks. Conclusions: The mixed pure tones were more advantageous than BBN as the sound therapy for tinnitus patients with normal to mild hearing loss. Significance: This trial provides a special and effective sound therapy method. Tinnitus patients with normal to mild hearing loss will experience more positive effects. Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR1800015554.
Histologic and Transcriptional Evidence of Subclinical Synovial Inflammation in Patients With Rheumatoid Arthritis in Clinical Remission

Patients with rheumatoid arthritis (RA) in clinical remission may have subclinical synovial inflammation. This study was undertaken to determine the proportion of patients with RA in remission or with low disease activity at the time of arthroplasty who had histologic or transcriptional evidence of synovitis, and to identify clinical features that distinguished patients as having subclinical synovitis.
Association between gaps in antihypertensive medication adherence and injurious falls in older community-dwelling adults: a prospective cohort study

Objective Growing evidence suggests that older adults are at an increased risk of injurious falls when initiating antihypertensive medication, while the evidence regarding long-term use of antihypertensive medication and the risk of falling is mixed. However, long-term users who stop and start these medications may have a similar risk of falling to initial users of antihypertensive medication. Our aim was to evaluate the association between gaps in antihypertensive medication adherence and injurious falls in older (≥65 years) community-dwelling, long-term (≥≥1 year) antihypertensive users. Design Prospective cohort study. Setting Irish Community Pharmacy. Participants Consecutive participants presenting a prescription for antihypertensive medication to 106 community pharmacies nationwide, community-dwelling, ≥65 years, with no evidence of cognitive impairment, taking antihypertensive medication for ≥1 year (n=938). Measures Gaps in antihypertensive medication adherence were evaluated from linked dispensing records as the number of 5-day gaps between sequential supplies over the 12-month period prior to baseline. Injurious falls during follow-up were recorded via questionnaire during structured telephone interviews at 12 months. Results At 12 months, 8.1% (n=76) of participants reported an injurious fall requiring medical attention. The mean number of 5-day gaps in medication refill behaviour was 1.47 (SD 1.58). In adjusted, modified Poisson models, 5-day medication refill gaps at baseline were associated with a higher risk of an injurious fall during follow-up (aRR 1.18, 95% CI 1.02 to 1.37, p=0.024). Conclusion Each 5-day gap in antihypertensive refill adherence increased the risk of self-reported injurious falls by 18%. Gaps in antihypertensive adherence may be a marker for increased risk of injurious falls. It is unknown whether adherence-interventions will reduce subsequent risk. This finding is hypothesis generating and should be replicated in similar populations.
Frequency of achieving a ‘ fit ’ cardiorespiratory fitness level and hypertension : a cohort study

Journal of Hypertension 2019, 37:820–826 Division of Biomedical Engineering for Health and Welfare, Tohoku University Graduate School of Biomedical Engineering, Aoba-ku, Sendai, Miyagi, Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku, Tokyo, Department of Psychosomatic Internal Medicine, Graduate Medical and Dental School, Kagoshima University, Kagoshima, Kagoshima, Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Tokyo Gas Co., Ltd., Minato-ku, Tokyo, Japan, Department of Epidemiology and Biostatistics and Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, USA
Comparison of Cortical Bone Trajectory Screw Placement Using the Midline Lumbar Fusion Technique to Traditional Pedicle Screws: A Case-Control Study

ABSTRACT Background: Cortical bone trajectory (CBT) screws are an alternative to traditional pedicle screws (PS) for lumbar fixation. The proposed benefits of CBT screws include decreased approach-related morbidity and greater cortical bone contact to prevent screw pullout. Relatively little data is published on this technique. Here, we compare the midline lumbar fusion (MIDLF) approach for CBT screw placement to transforaminal lumbar interbody fusion (TLIF) for traditional PS placement. Methods: A prospectively maintained institutional database was retrospectively reviewed for all patients undergoing lumbar spinal fusion using CBT screws over the past 5 years. Controls were identified from the same database as patients undergoing lumbar spinal fusion with traditional PS placement and matched based on age, sex, and number of levels fused. Exclusion criteria included prior lumbar instrumentation. The electronic health record was retrospectively reviewed for demographic, perioperative, and postoperative data. Results: A total of 23 patients who underwent CBT screw placement and 35 controls who received traditional PS were included in the study. The median follow-up time was 52.5 months. The CBT screw group had significantly less mean estimated blood loss than the PS group (186 mL versus 414 mL respectively; P = .008). Both groups experienced significant improvements in preoperative Oswestry Disability Index (ODI) and visual analog scale (VAS) scores for back and leg pain. However, there was no significant difference between the groups in regard to operative time and amount of improvement in VAS pain score or ODI. The CBT group was associated with a significantly shorter mean length of stay (LOS). There were 2 instances of screw pullout in each group. Conclusions: The MIDLF approach with CBT screw placement is associated with less intraoperative blood loss and shorter LOS than traditional PS placement. There is no difference between the 2 techniques in regard to improvement in pain or disability.
The Impact of a Community‐Based Serious Illness Care Program on Healthcare Utilization and Patient Care Experience

Healthcare organizations are expanding community‐based serious illness care programs to deliver care for homebound patients. Programs typically focus on home‐based primary care or home‐based palliative care, yet this population may require both services. We developed and evaluated a primary and palliative care program serving seriously ill older adults, called the Reaching Out to Enhance the Health of Adults in Their Communities and Homes (REACH) program. Our objective was to determine the impact of the REACH program on healthcare utilization and the patient care experience.