Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Follow-Up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma.

PURPOSE The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a highly effective and convenient induction regimen for both transplantation-eligible and -ineligible patients with myeloma. Here, we present the largest cohort of patients consecutively treated with RVD induction therapy followed by risk-adapted maintenance therapy with the longest follow-up and important information on long-term outcomes. PATIENTS AND METHODS We describe 1,000 consecutive patients with newly diagnosed myeloma treated with RVD induction therapy from January 2007 until August 2016. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. RESULTS The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively. CONCLUSION RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes. This study includes the largest cohort of patients treated with RVD reported to date with long follow-up and demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.
Estimating genetic diversity and population structure of 22 chicken breeds in Asia using microsatellite markers

Objective Estimating the genetic diversity and structures, both within and among chicken breeds, is critical for the identification and conservation of valuable genetic resources. In chickens, microsatellite (MS) marker polymorphisms have previously been widely used to evaluate these distinctions. Our objective was to analyze the genetic diversity and relationships among 22 chicken breeds in Asia based on allelic frequencies. Methods We used 469 genomic DNA samples from 22 chicken breeds from eight Asian countries (South Korea, KNG, KNB, KNR, KNW, KNY, KNO; Laos, LYO, LCH, LBB, LOU; Indonesia, INK, INS, ING; Vietnam, VTN, VNH; Mongolia, MGN; Kyrgyzstan, KGPS; Nepal, NPS; Sri Lanka, SBC) and three imported breeds (RIR, Rhode Island Red; WLG, White Leghorn; CON, Cornish). Their genetic diversity and phylogenetic relationships were analyzed using 20 MS markers. Results In total, 193 alleles were observed across all 20 MS markers, and the number of alleles ranged from 3 (MCW0103) to 20 (LEI0192) with a mean of 9.7 overall. The NPS breed had the highest expected heterozygosity (Hexp, 0.718±0.027) and polymorphism information content (PIC, 0.663±0.030). Additionally, the observed heterozygosity (Hobs) was highest in LCH (0.690±0.039), whereas WLG showed the lowest Hexp (0.372±0.055), Hobs (0.384±0.019), and PIC (0.325±0.049). Nei’s DA genetic distance was the closest between VTN and VNH (0.086), and farthest between KNG and MGN (0.503). Principal coordinate analysis showed similar results to the phylogenetic analysis, and three axes explained 56.2% of the variance (axis 1, 19.17%; 2, 18.92%; 3, 18.11%). STRUCTURE analysis revealed that the 22 chicken breeds should be divided into 20 clusters, based on the highest ΔK value (46.92). Conclusion This study provides a basis for future genetic variation studies and the development of conservation strategies for 22 chicken breeds in Asia.
Endogenous enzyme activities and tibia bone development of broiler chickens fed wheat-based diets supplemented with xylanase, β-glucanase and phytase

Objective This study assessed the effect of different levels of xylanase, β-glucanase and phytase on intestinal enzyme activities and tibia bone development in broiler chickens fed wheat-based diets. Methods Twelve experimental diets were formulated using a 3×2×2 factorial design (three doses of phytase and two doses of both xylanase and β-glucanase) and offered to 648 day-old Ross 308 male chicks having 6 replicates groups with 9 birds per replicate and lasted for 35 days. Results An interaction between the enzymes products improved (p<0.01) the activity of chymotrypsin. Protein content at d 10 was highest (p<0.001) with addition of phytase while general proteolytic activity (GPA) (p<0.02) and lipase activity (p<0.001) were decreased. At d 24, there were improvements in protein content (p<0.01) and lipase (p<0.04) with supplementation of superdose phytase. Addition of superdose phytase decreased in chymotrypsin (p<0.02), trypsin (p<0.01) and GPA (p<0.001). The optimum dose of xylanase decreased the chymotrypsin activity (p = 0.05), while the GPA (p<0.001) was increased with the optimum level of β-glucanase. Superdose phytase supplementation at d 10 improved maltase (p = 0.05), sucrase (p<0.001) and alkaline phosphatase (p<0.001) activities in the jejunum while aminopeptidase activity was highest (p<0.005) with the low level of phytase. Protein content of jejunum mucosa was bigger (p<0.001) in birds fed superdose phytase while maltase activity (p<0.001) at d 24 was reduced by this treatment. Sucrase (p<0.04) and aminopeptidase activities (p<0.001) improved when diets supplemented with low levels of phytase. Tibia bone breaking strength was highest (p<0.04) with addition of low level of superdose phytase or optimum level of β-glucanase. Bone dry matter content decreased (p<0.04) when diets supplemented with phytase. Conclusion From the results obtained in this study, supplementation of superdose phytase was the most effective, however, the cost-benefit analysis of the use of such a dose needs to be evaluated.
Bioactive indanes: insight into the bioactivity of indane dimers related to the lead anti-inflammatory molecule PH46A

PH46A (1) demonstrates significant anti‐inflammatory activity in phenotypic models but its mechanism and site of action have been elusive. Current study focused on the bioactivity of PH46 (2) and related novel indane dimers (6‐10) to investigate the impact of changes in substitution and stereochemistry at the C‐1 and C‐2 positions of the PH46 (2) scaffold.
IL-1β Suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury.

Unchecked inflammation is a hallmark of inflammatory tissue injury in diseases such as acute respiratory distress syndrome (ARDS). Yet the mechanisms of inflammatory lung injury remain largely unknown. Here we showed that bacterial endotoxin lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced polymicrobial sepsis decreased the expression of transcription factor cAMP Response Element Binding (CREB) in lung endothelial cells. We demonstrated that endothelial CREB was crucial for VE-cadherin transcription and the formation of the normal restrictive endothelial adherens junctions. The inflammatory cytokine IL-1β reduced cAMP generation and CREB-mediated transcription of VE-cadherin. Furthermore, endothelial cell-specific deletion of CREB induced lung vascular injury whereas ectopic expression of CREB in the endothelium prevented the injury. We also observed that rolipram, which inhibits PDE4-mediated hydrolysis of cAMP, prevented endotoxemia-induced lung vascular injury since it preserved CREB-mediated VE-cadherin expression. These data demonstrate the fundamental role of endothelial cAMP-CREB axis in promoting lung vascular integrity and suppressing inflammatory injury. Therefore, strategies aimed at enhancing endothelial CREB-mediated VE-cadherin transcription are potentially useful in preventing sepsis-induced lung vascular injury in ARDS.
A taxonomic revision of Deronectes Sharp, 1882 (Insecta: Coleoptera: Dytiscidae) (part 1)

The second part of the revision of Deronectes SHARP, 1882, provides synonymy, a key for determination, and descriptions and distributional data for the species of the D. parvicollis-group. This group is divided into the D. parvicollis-, D. afghanicus-, D. longipesand D. y'aec7z/-subgroups. Fourteen species are described as new: Deronectes balkei sp.n. , Deronectes bilioni sp.n. , Deronectes brancuccii sp.n. , Deronectes elmii sp.n. , Deronectes hendrichi sp.n. , and Deronectes youngi sp.n. from Iran, Deronectes danielssoni sp.n. and Deronectes roberti sp.n. from Afghanistan, Deronectes evelynae sp.n. and Deronectes hebaueri sp.n. from Turkey, Deronectes riberai sp.n. from Turkey and Iraq, Deronectes kinzelbachi sp.n. from Turkey and Syria, Deronectes palaestinus sp.n. from Syria, and Deronectes bameuli sp.n. from Pakistan. Therefore genus Deronectes now contains 53 species in total. Deronectes parvicollis (SCHAUM, 1864) is newly recorded from Macedonia, Armenia, Georgia and Iran, and Deronectes abnormicollis SEMENOW, 1900, is recorded from China for the first time (see also FERY & BRANCUCCI 1997: 220). The females of Deronectes jaechi WEWALKA, 1989, Deronectes persicus PESCHET, 1914, and Deronectes vestitus (GEBLER, 1848) are described for the first time.
Endovascular Thrombectomy for Low ASPECTS Large Vessel Occlusion Ischemic Stroke: A Systematic Review and Meta-Analysis

ABSTRACT: Background: The current American Heart Association guidelines for acute ischemic stroke reserve Grade 1A recommendation for the use of endovascular thrombectomy (EVT) for patients with an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of ≥6. Objective: We aim to determine the safety and efficacy of EVT for large vessel occlusion ischemic stroke patients with low ASPECTS (5 or less). Methods: Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for studies appraising the outcomes of EVT for low ASPECTS ischemic stroke. A meta-analysis of proportions compared the clinical outcomes of patients undergoing EVT and those receiving best medical therapy only. Results: Nine studies (1,196 patients) were included. There was a trend (p = 0.11) toward a higher rate of symptomatic intracranial hemorrhage (sICH) in the EVT group (9.2%; 95% CI 6.1–13.6; I2 53.37%) compared to the medical group (5.5%; 95% CI 3.7–8.1; I2 0%). There was no difference (p = 0.41) in the pooled 90-day mortality of EVT patients (30.7%; 95% CI 21.7–41.5; I2 84.23%) and medical patients (36.6%; 95% CI 26.4–48.1; I2 76.2%). EVT patients had better (p = 0.001) 90-day outcomes, with 27.7% (95% CI 21.8–34.5; I2 62.08%) of patients attaining a modified Rankin Scale of 0–2 compared to only 3.7% (95% CI 2.3–5.9; I2 87.21%) in the medical group. Conclusions: This meta-analysis demonstrates a trend in higher sICH among low ASPECTS patients undergoing EVT. Despite this, a significant proportion of this subset of patients still achieved good functional outcomes at 90 days. Randomized trials are necessary to substantiate this result as significant bias is inherent in the observational studies included in this review.
Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy

Conventional immunohistochemistry (IHC) is a widely used diagnostic technique in tissue pathology. However, this technique is associated with a number of limitations, including high inter‐observer variability and the capacity to label only one marker per tissue section. This review details various highly multiplexed techniques that have emerged to circumvent these constraints, allowing simultaneous detection of multiple markers on a single tissue section and the comprehensive study of cell composition, cellular functional and cell‐cell interactions. Among these techniques, multiplex Immunohistochemistry/Immunofluorescence (mIHC/IF) has emerged to be particularly promising. mIHC/IF provides high‐throughput multiplex staining and standardized quantitative analysis for highly reproducible, efficient and cost‐effective tissue studies. This technique has immediate potential for translational research and clinical practice, particularly in the era of cancer immunotherapy.
BOLD and GenBank revisited – Do identification errors arise in the lab or in the sequence libraries?

Applications of biological knowledge, such as forensics, often require the determination of biological materials to a species level. As such, DNA-based approaches to identification, particularly DNA barcoding, are attracting increased interest. The capacity of DNA barcodes to assign newly encountered specimens to a species relies upon access to informatics platforms, such as BOLD and GenBank, which host libraries of reference sequences and support the comparison of new sequences to them. As parameterization of these libraries expands, DNA barcoding has the potential to make valuable contributions in diverse applied contexts. However, a recent publication called for caution after finding that both platforms performed poorly in identifying specimens of 17 common insect species. This study follows up on this concern by asking if the misidentifications reflected problems in the reference libraries or in the query sequences used to test them. Because this reanalysis revealed that missteps in acquiring and analyzing the query sequences were responsible for most misidentifications, a workflow is described to minimize such errors in future investigations. The present study also revealed the limitations imposed by the lack of a polished species-level taxonomy for many groups. In such cases, applications can be strengthened by mapping the geographic distributions of sequence-based species proxies rather than waiting for the maturation of formal taxonomic systems based on morphology.
Variation of colorectal, breast and prostate cancer screening activity in Switzerland: Influence of insurance, policy and guidelines

Variation in utilization of healthcare services is influenced by patient, provider and healthcare system characteristics. It could also be related to the evidence supporting their use, as reflected in the availability and strength of recommendations in clinical guidelines. In this study, we analyzed the geographic variation of colorectal, breast and prostate cancer screening utilization in Switzerland and the influence of available guidelines and different modifiers of access. Colonoscopy, mammography and prostate specific antigen (PSA) testing use in eligible population in 2014 was assessed with administrative claims data. We ran a multilevel multivariable logistic regression model and calculated Moran’s I and regional level median odds ratio (MOR) statistics to explore residual geographic variation. In total, an estimated 8.1% of eligible persons received colonoscopy, 22.3% mammography and 31.3% PSA testing. Low deductibles, supplementary health insurance and enrollment in a managed care plan were associated with higher screening utilization. Cantonal breast cancer screening programs were also associated with higher utilization. Spatial clustering was observed in the raw regional utilization of all services, but only for prostate cancer screening in regional residuals of the multilevel model. MOR was highest for prostate cancer screening (1.24) and lowest for colorectal cancer screening (1.16). The reasons for the variation of the prostate cancer screening utilization, not recommended routinely without explicit shared decision-making, could be further investigated by adding provider characteristics and patient preference information. This first cross-comparison of different cancer screening patterns indicates that the strength of recommendations, mediated by specific health policies facilitating screening, may indeed contribute to variation.
Adaptive Control of Dynamic Balance across the Adult Lifespan

Supplemental digital content is available in the text. ABSTRACT Introduction The ability to adapt dynamic balance to perturbations during gait deteriorates with age. To prevent age-related decline in adaptive control of dynamic balance, we must first understand how adaptive control of dynamic balance changes across the adult lifespan. We examined how adaptive control of the margin of stability (MoS) changes across the lifespan during perturbed and unperturbed walking on the split-belt treadmill. Methods Seventy-five healthy adults (age range, 18–80 yr) walked on an instrumented split-belt treadmill with and without split-belts. Linear regression analyses were performed for the mediolateral (ML) and anteroposterior (AP) MoS, step length, single support time, step width, double support time, and cadence during unperturbed and perturbed walking (split-belt perturbation), with age as predictor. Results Age did not significantly affect dynamic balance during unperturbed walking. However, during perturbed walking, the ML MoS of the leg on the slow belt increased across the lifespan due to a decrease in bilateral single support time. The AP MoS did not change with aging despite a decrease in step length. Double support time decreased and cadence increased across the lifespan when adapting to split-belt walking. Age did not affect step width. Conclusions Aging affects the adaptive control of dynamic balance during perturbed but not unperturbed treadmill walking with controlled walking speed. The ML MoS increased across the lifespan, whereas bilateral single support times decreased. The lack of aging effects on unperturbed walking suggests that participants’ balance should be challenged to assess aging effects during gait. The decrease in double support time and increase in cadence suggests that older adults use the increased cadence as a balance control strategy during challenging locomotor tasks.
Online HOPE intervention on mental health literacy among youths in Singapore: An RCT protocol.

AIMS The study aims to examine the effectiveness of the online HOPE intervention to increase mental health literacy, psychological well-being; and in reducing stress among youths aged 18 - 24 living in Singapore. DESIGN The study will be conducted in two phases. The first phase will adopt a single-group pre-post repeated quasi-experimental research design. The second phase adopts a two-group, parallel randomized control trial, with a pre-test, post-test and follow-up. METHODS The study will be conducted in a University in Singapore, in 2019-2021. Participants will be recruited and randomly assigned into one of the two groups. Approval from the institutional review board has been obtained in August 2019. Research funding from National Youth Fund has been obtained in November 2019. Outcome measures will be measured using Depression Literacy Questionnaire, Anxiety literacy Questionnaire, validated depression vignette, Ryff's psychological well-being Scale and Perceived Stress Scale, at baseline, post intervention and two months' follow-up. Participants' perceptions of the intervention will be measured qualitatively. DISCUSSION The online HOPE intervention had been developed based on the principles of the Self-Efficacy Theory. IMPACT There is no research about mental health literacy intervention in Singapore. Low mental health literacy prevents early help-seeking and delays treatment. Hence, this study highlights the importance of mental health public education as primary care. Increased mental health literacy will enhance early help-seeking behaviors, promoting early recovery and enhancing the health of the young people worldwide. The RCT has been registered at ClinicalTrials.gov: NCT04266119.
Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID‐19 Pandemic: AASLD Expert Panel Consensus Statement

Coronavirus disease 2019 (COVID‐19), the illness caused by the SARS‐CoV‐2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID‐19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID‐19 pandemic on liver patients and healthcare providers.
Whole-Blood Levels of MicroRNA-9 Are Decreased in Patients With Late-Onset Alzheimer Disease

Recent evidence suggests changes in circulating microRNA levels may be promising biomarkers for the clinical diagnosis of Alzheimer disease (AD). We hypothesized that whole-blood microRNAs may be useful to identify individuals with established AD. For this purpose, a sample of community-dwelling women (≥55 years old) carrying the ApoE ∊4 allele were clinically evaluated using the American Psychiatric Association/Diagnostic and Statistical Manual of Mental Disorders, Fourth edition and the Alzheimer Disease Assessment Scale–Cognitive Subscale criteria to diagnose probable AD, and the Clinical Dementia Rating scale to stage the dementia. A set of 25 mature microRNAs was rationally selected for evaluation based on experimental evidence of interaction with genes linked to the late-onset AD neuropathology. Whole-blood concentrations were determined by quantitative real-time polymerase chain reaction. Compared to patients without dementia, a median 3-fold decrease in miR-9 levels was found among patients with AD (P = .001). Our findings support blood-borne miR-9 as a candidate biomarker for probable AD, embodied by evidence from the literature of its implication in amyloidogenesis.
Racial Disparities in Health Care Utilization at the End of Life Among New Jersey Medicaid Beneficiaries With Advanced Cancer.

PURPOSE Racial and ethnic disparities in cancer care near the end of life (EOL) have been recognized, but EOL care experienced by Medicaid beneficiaries is not well understood. We assessed the prevalence of aggressive EOL care and hospice enrollment for Medicaid beneficiaries and determined whether racial and ethnic disparities exist. PATIENTS AND METHODS We identified Medicaid beneficiaries (age 21-64 years) who were diagnosed from 2011 to 2015 with stage IV breast and colorectal cancer and who died by January 2016 through a New Jersey State Cancer Registry-Medicaid claims linked data set. We measured aggressive EOL care (> 1 hospitalization, > 1 emergency department [ED] visit, any intensive care unit [ICU] admission in the last 30 days of life, and receipt of chemotherapy in the last 14 days of life) and hospice enrollment. Multivariable logistic regression models were used to determine factors associated with aggressive EOL care and hospice enrollment. RESULTS Of the 349 patients, 217 (62%) received at least one of the following measures of aggressive EOL care: > 1 hospitalization (27%), > 1 ED visit (31%), ICU admission (30%), and chemotherapy (34%). The adjusted odds of receiving any aggressive care were 1.87 times higher (95% CI, 1.08 to 3.26) for non-Hispanic (NH) black patients compared with NH white patients. Only 39% of patients enrolled in hospice. No significant differences in hospice enrollment were observed by race or ethnicity. CONCLUSION The majority of Medicaid patients with advanced cancer received aggressive EOL care and were not enrolled in hospice. NH black patients were more likely to receive aggressive EOL care. Further work to understand processes leading to suboptimal EOL care within Medicaid populations and among racial and ethnic minority groups is warranted.