Miracle-dz/UniFAR-FTUs huggingface dataset:
Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: a prospective observational study

Background Augmented renal clearance (ARC) is common in critically ill patients and could result in subtherapeutic antibiotic concentration. However, data in the Asian population are still lacking. The aim of this study was to explore the incidence and risk factors of ARC and its effect on β-lactam pharmacokinetics/pharmacodynamics (PK/PD) in Asian populations admitted to a medical ICU. In addition, we evaluated the appropriateness of using three estimated glomerular filtration (eGFR) formulas [Cockcroft–Gault (CG), Modification of Diet in Renal Disease (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] as screening tools. Methods We measured 2-, 8-, and 24-hr creatinine clearance (CLCr) and calculated eGFR by using three formulas for each. ARC was defined as CLCr24hr >130 mL/min/1.73 m2. Concentrations at the mid-dosing interval and prior to the next dose were collected if patients received the β-lactam antibiotic of piperacillin/tazobactam, cefepime, and meropenem, to determine the PK/PD index of fT > MIC. Multiple logistic regression analysis was conducted to identify the risk factors for ARC. Pearson correlation coefficient and the Bland and Altman method were applied to assess the accuracy of CLCr2hr, CLCr8hr, and eGFR for predicting ARC. Results Of 100 patients, 46 (46%) manifested ARC. Younger age (<50 years) and lower Sequential Organ Failure Assessment score increased the likelihood of ARC. ARC resulted in a low chance of achieving 50% fT >4MIC (33% vs 75%, p<0.01), 100% fT > MIC (23% vs 69%, p<0.01), and 100% fT >4MIC (3% vs 25%, p<0.02). CLCr8hr wielded the best correlation and agreement with CLCr24hr. eGFRCG was the most appropriate screening tool, and the optimal cutoff value for detecting ARC was 130.5 mL/min/1.73 m2. Conclusion ARC is associated with inadequate β-lactam PK/PD target in Asian ICU.
Interferon pathway in SLE: one key to unlocking the mystery of the disease

SLE is characterised by an activation of the interferon (IFN) system, which leads to an increased expression of IFN-regulated genes. The reasons behind the IFN signature in SLE are (1) the existence of endogenous IFN inducers, (2) activation of several IFN-producing cell types, (3) production of many different IFNs, (4) a genetic setup promoting IFN production and (5) deficient negative feedback mechanisms. The consequences for the immune system is a continuous stimulation to an immune response, and for the patient a number of different organ manifestations leading to typical symptoms for SLE. In the current review, we will present the existing knowledge of the IFN system and pathway activation in SLE. We will also discuss how this information can contribute to our understanding of both the aetiopathogenesis and some organ manifestations of the disease. We will put forward some issues that are unresolved and should be clarified in order to make a proper stratification of patients with SLE, which seems important when selecting a therapy aiming to downregulate the IFN system.
Current practices of health care providers in recommending online resources for chronic pain self-management

Purpose Online health resources (websites, apps and social media) may be an adjunct to provide self-management support for people with persistent or chronic pain. Endorsement of online health resources by health care providers is crucial for uptake by end-users. The aim of this study was to investigate the current practices of New Zealand (NZ) health care providers in recommending online resources for persistent pain management, and to identify what factors predict health care providers’ recommendations and to explore the common concerns. Methods An online survey of NZ health care providers (ie, chiropractors, general practitioners, nurses, occupational therapists, osteopaths, physiotherapists, psychologists, specialist consultants, and social workers) involved in the management of persistent pain was conducted. The recruitment strategy was tailored to each occupation via occupation-specific professional organizations, and by approaching multidisciplinary professional organizations. Results Data from 213 health care providers were used in the final analysis. Most of the health care providers were physiotherapists (n=71), followed by chiropractors (n=39) and general practitioners (n=31). Fifty three percent (111/210) of health care providers reported currently recommending online resources. A multivariate logistic regression model showed that specialist interest in treating pain (OR=3.84; 95% CI: 1.66, 8.87; P=0.002), and level of confidence in recommending online resources (OR=1.05; CI: 1.04, 1.07; P<0.001), positively influenced recommending online resources. The majority of the health care providers (65%, 138/213) were concerned about the safety issues related to the risk of patients misinterpreting online information and to the lack of evidence-based information. Conclusion Half of the health care providers surveyed reported recommending online resources, which may suggest limited confidence in recommending, or knowledge of, existing online resources for persistent pain management. Ongoing education for health care providers on evidence-based online resources is required to recommend online resources as a self-management support tool for people with persistent pain.
Effects of Parity and Breast Feeding Duration on the Risk of Osteoporosis in Postmenopausal Korean Women: A Systematic Review and Meta-Analysis

Objectives To summarize the evidence regarding the association of parity and breast feeding duration with the risk of osteoporosis in postmenopausal Korean women. This was because studies have been inconsistent regarding the effect of parity and breast feeding duration on the risk of osteoporosis. Methods A systematic literature search of relevant studies published by December 26, 2018 was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL, RISS, KISS, KMbase, and KoreaMed. Outcome estimates of odds ratio (OR) or standardized mean difference were pooled with fixed or random-effect model. In case of heterogeneity, subgroup analysis was conducted. Results Seven cross-sectional studies (with 3,813 subjects) were included in the analysis. OR for osteoporosis was 1.43 (95% confidence interval [CI] = 1.09–1.88, P = 0.010) in postmenopausal women with higher parity compared to those with less parity. Moreover, OR for osteoporosis was 1.93 (95% CI = 1.28–2.93, P = 0.002) in postmenopausal women with longer durations of breast feeding than in those with shorter durations of breast feeding. Conclusions This study revealed that duration of breast feeding increased the risk of osteoporosis in postmenopausal Korean women. More cohort studies with high quality research designs are needed to confirm our results.
Thermal and mechanical quantitative sensory testing values among healthy African American adults

Purpose Only a few studies have reported quantitative sensory testing (QST) reference values for healthy African Americans, and those studies are limited in sample size and age of participants. The study purpose was to characterize QST values in healthy, pain-free African American adults and older adults whose prior pain experiences and psychological status were also measured. We examined the QST values for differences by sex, age, and body test site. Patients and methods A cross-sectional sample of 124 pain-free African American adults (age 18–69 years, 49% female) completed demographic and self-reported pain, fatigue and psychosocial measures. QST was performed to obtain thermal and mechanical responses and associated pain intensity levels. Results We found thermal detection values at the anterior forearm were (29.2 °C±1.6) for cool detection (CD) and (34.5 °C±1.2) for warm detection (WD). At that site the sample had cold pain threshold (CPTh) (26.3 °C±5.0), heat pain threshold (HPTh) (37.8 °C±3.6), and mechanical pain thresholds (MPTH) (16.7±22.2 grams of force, gF). There was a significant between sex difference for WD, with women being more sensitive (q=0.027). Lower body sites were less sensitive than upper body sites across all thermal modalities (q<0.003), but not for the mechanical modality. Conclusion The QST values from this protocol at the anterior forearm indicate that the healthy African American adults had average thermal pain thresholds close to the temperature of adaptation and average MPTh under 20 gF. Differences in responses to thermal and mechanical stimuli for upper verses lower body were consistent with prior research.
Magnetization switching using topological surface states

With a topological insulator/magnetic insulator bilayer, we demonstrate topological surface state–driven magnetization switching. Topological surface states (TSSs) in a topological insulator are expected to be able to produce a spin-orbit torque that can switch a neighboring ferromagnet. This effect may be absent if the ferromagnet is conductive because it can completely suppress the TSSs, but it should be present if the ferromagnet is insulating. This study reports TSS-induced switching in a bilayer consisting of a topological insulator Bi2Se3 and an insulating ferromagnet BaFe12O19. A charge current in Bi2Se3 can switch the magnetization in BaFe12O19 up and down. When the magnetization is switched by a field, a current in Bi2Se3 can reduce the switching field by ~4000 Oe. The switching efficiency at 3 K is 300 times higher than at room temperature; it is ~30 times higher than in Pt/BaFe12O19. These strong effects originate from the presence of more pronounced TSSs at low temperatures due to enhanced surface conductivity and reduced bulk conductivity.
OSM-induced CD44 contributes to breast cancer metastatic potential through cell detachment but not epithelial-mesenchymal transition

Background Hormone receptor status in human breast cancer cells is a strong indicator of the aggressiveness of a tumor. Triple negative breast cancers (TNBC) are aggressive, difficult to treat, and contribute to high incidences of metastasis by possessing characteristics such as increased tumor cell migration and a large presence of the transmembrane protein, cluster of differentiation 44 (CD44) on the cell membrane. Estrogen receptor-positive (ER+) cells are less aggressive and do not migrate until undergoing an epithelial-mesenchymal transition (EMT). Methods The relationship between EMT and CD44 during metastatic events is assessed by observing changes in EMT markers, tumor cell detachment, and migration following cytokine treatment on both parental and CD44 knockdown human breast tumor cells. Results ER+ T47D and MCF-7 human breast cancer cells treated with OSM demonstrate increased CD44 expression and CD44 cleavage. Conversely, ER- MDA-MB-231 human breast cancer cells do not show a change in CD44 expression nor undergo EMT in the presence of OSM. In ER+ cells, knockdown expression of CD44 by shRNA did not prevent EMT but did change metastatic processes such as cellular detachment and migration. OSM-induced migration was decreased in both ER+ and ER- cells with shCD44 cells compared to control cells, while the promotion of tumor cell detachment by OSM was decreased in ER+ MCF7-shCD44 cells, as compared to control cells. Interestingly, OSM-induced detachment in ER- MDA-MB-231-shCD44 cells that normally don’t detach at significant rates. Conclusion OSM promotes both EMT and tumor cell detachment in ER+ breast cancer cells. Yet, CD44 knockdown did not affect OSM-induced EMT in these cells, while independently decreasing OSM-induced cell detachment. These results suggest that regulation of CD44 by OSM is important for at least part of the metastatic cascade in ER+ breast cancer.
A Definition of Significant Instability and a Scoring System for Predicting Meniscal Tears in ACL-Deficient Knees

Background: Patients with anterior cruciate ligament (ACL)–deficient knees risk recurrent instability of the affected knee, which may predispose to meniscal injuries. Various studies have correlated the incidence of meniscal tear with elapsed time from ACL tear and number of instability events. However, it is not clear how significant an instability event needs to be to contribute to a meniscal tear. Purpose/Hypothesis: The purpose of this study was to (1) define a significant instability episode and (2) develop a checklist and scoring system for predicting meniscal tears based on significant instability episode. We hypothesized that patients with ACL-deficient knees who met the scoring threshold for a significant instability episode would have a higher incidence of meniscal tears compared with those who did not meet the threshold. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: This retrospective study included patients with magnetic resonance imaging (MRI)–confirmed isolated ACL tear for longer than 3 months. We determined parameters for assessing instability episodes and defined any instability events between the MRI and ACL reconstruction as significant or insignificant. Patients were then grouped into a significant instability group (≥1 significant episode) and an insignificant instability group, and the incidence and types of meniscal tears found during surgery were compared between groups. Results: There were 108 study patients: 62 in the significant instability group and 46 in the insignificant instability group. During surgery, 58 meniscal tears (46 medial, 12 lateral) were recorded, for an overall meniscal injury rate of 53.70%. In the significant instability group, 47 patients (75.81%) had a meniscal tear and 15 (24.19%) had intact menisci (P < .001). In the insignificant instability group, 11 patients (23.91%) had a meniscal tear and 35 (76.08%) had intact menisci (P < .001). Regarding the 58 patients with a meniscal tear, 47 (81.03%) had ≥1 significant episode of instability before surgery, as compared with 11 (18.97%) who had insignificant or no instability. The odds of having a medial meniscal tear at ACL reconstruction was 10 times higher in the significant instability group versus the insignificant instability group. Conclusion: The incidence of a medial meniscal tear was 10 times greater in patients with a significant episode of instability versus those with insignificant instability, as defined using a predictive scoring system. The incidence of lateral meniscal tear did not change with instability episodes.
Proliferative, pro-inflammatory, and angiogenesis regulator gene expression profile defines prognosis in different histopathological subtypes of nodal peripheral T-cell lymphoma

Nodal peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous malignancy with poor prognosis. We studied the prognostic impact of the expression profile of genes related to cell proliferation (CCNA2, TOP2A, and CHEK1), pro-inflammatory activity (NFkB1 and IKBkB), and angiogenesis (VEGF1) in nodal PTCL outcomes, as well as the ability of this genomic panel to discriminate different histological subtypes. We investigated the relative expression of regulator genes in 63 nodal PTCL patients. CCNA2, TOP2A, CHEK1, and NF-kB1 proteins were also assessed by immunohistochemistry. The median patient age was 47 years, 57.1% were male, 34.9% were diagnosed with PTCL-NOS, 28.6% with ALK-/ALCL, 22.2% with ALK+/ALCL, and 14.3% with AITL. The proliferative genes were associated with worse 3-year OS and PFS in PTCL-NOS and better 3-year PFS in ALK-/ALCL. Expression of CCNA2≥median and overexpression of CHEK1 protein (HR 3.793; p = 0.007) were associated with worse OS for all the cohort of nodal PTCL (HR 1.418; p = 0.001). The genomic expression profile tested in this study was not able to discriminate the different subtypes of nodal PTCL, although it showed a distinct prognostic significance between PTCL-NOS and ALCL-ALK. Overexpression of the CCNA2 gene and CHEK1 protein were associated with poor prognosis in the total nodal PTCL cohort.
Phylogenomic analyses confirm a novel invasive North American Corbicula (Bivalvia: Cyrenidae) lineage

The genus Corbicula consists of estuarine or freshwater clams native to temperate/tropical regions of Asia, Africa, and Australia that collectively encompass both sexual species and clonal (androgenetic) lineages. The latter have become globally invasive in freshwater systems and they represent some of the most successful aquatic invasive lineages. Previous studies have documented four invasive clonal lineages, Forms A, B, C, and Rlc, with varying known distributions. Form A (R in Europe) occurs globally, Form B is found solely in North America, mainly the western United States, Form C (S in Europe) occurs both in European watersheds and in South America, and Rlc is known from Europe. A putative fifth invasive morph, Form D, was recently described in the New World from the Illinois River (Great Lakes watershed), where it occurs in sympatry with Forms A and B. An initial study showed Form D to be conchologically distinct: possessing rust-colored rays and white nacre with purple teeth. However, its genetic distinctiveness using standard molecular markers (mitochondrial cytochrome c oxidase subunit I and nuclear ribosomal 28S RNA) was ambiguous. To resolve this issue, we performed a phylogenomic analysis using 1,699–30,027 nuclear genomic loci collected via the next generation double digested restriction-site associated DNA sequencing method. Our results confirmed Form D to be a distinct invasive New World lineage with a population genomic profile consistent with clonality. A majority (7/9) of the phylogenomic analyses recovered the four New World invasive Corbicula lineages (Forms A, B, C, and D) as members of a clonal clade, sister to the non-clonal Lake Biwa (Japan) endemic, Corbicula sandai. The age of the clonal clade was estimated at 1.49 million years (my; ± 0.401–2.955 my) whereas the estimated ages of the four invasive lineage crown clades ranged from 0.27 to 0.44 my. We recovered very little evidence of nuclear genomic admixture among the four invasive lineages in our study populations. In contrast, 2/6 C. sandai individuals displayed partial nuclear genomic Structure assignments with multiple invasive clonal lineages. These results provide new insights into the origin and maintenance of clonality in this complex system.
Effect of high-frequency vibration on orthodontic tooth movement and bone density

OBJECTIVES: Previous reports have shown that high-frequency vibration can increase bone remodeling and accelerate tooth movement. The aim of this study was to evaluate the effects of high-frequency vibration on treatment phase tooth movement, and post-treatment bone density at initiation of retention, with cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Thirty patients with initial Class I skeletal relationships, initial minimum-moderate crowding (3–5 mm), treated to completion with clear aligners and adjunctive high-frequency vibration, (HFV group) or no vibration, (Control group) were evaluated. The patients were instructed to change aligners as soon as they become loose. Changes in bone density associated with orthodontic treatment were evaluated using i-CAT cone-beam computed tomography (CBCT) and InVivo Anatomage® software to quantify density using Hounsfield units (HU) between treated teeth in 10 different regions. HU values were averaged and compared against baseline (T1) and between the groups at initiation of retention (T2). RESULTS: The average time for aligner change was 5.2 days in the HFV group, and 8.7 days in the control group (P = 0.0001). There was significant T1 to T2 increase of HU values in the upper arch (P = 0.0001) and the lower arch (P = 0.008) in the HFV group. There was no significant change in average HU values in the upper (P = 0.83) or lower arches (P = 0.33) in the control group. The intergroup comparison revealed a significant difference in the upper, (P = 0.0001) and lower arches (P = 0.007). CONCLUSION: High-frequency vibration adjunctive to clear aligners, allowed early aligner changes that led to shorter treatment time in minimum-moderate crowded cases. At initiation of retention, the HFV group demonstrated statistically significant increase as compared with pre-treatment bone density, whereas control subjects showed no significant change from pre-treatment bone density.
Evaluation of enzyme activity and rate of tooth movement in corticotomy-accelerated tooth movement – A randomized clinical trial

BACKGROUND: This study was undertaken to evaluate the enzyme activity profiles in human saliva and gingival crevicular fluid (GCF) in accelerated tooth movement when compared with normal orthodontic tooth movement (OTM) in extraction cases. MATERIALS AND METHODS: Twenty patients who required premolar extractions were treated with MBT mechanotherapy. They were divided into two equal groups: conventional (Group I) and corticotomy (Group II) which was performed on both the jaw sides before initiating retraction. GCF was collected from mesial and distal aspects of canine before initiation of retraction and at 7th, 14th, 21st, and 28th days, and then at fifth and sixth weeks and third and sixth months after retraction. A total of 5 mL of unstimulated saliva was collected from the subjects after 90 min of nonoral activity (subjects were refrained from eating and drinking). RESULTS: The results showed that in Group I, the peak of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) enzyme activity occurred on the 14th day of force application. In Group II, the enzyme activity progressively increased from day 0 to 6 weeks, peaking at the sixth week, and then a decline in enzyme activity was observed on third and sixth months. When ALP and AST activities in GCF and saliva were compared between Groups I and II, no statistically significant difference was observed on days 0, 7, and 14. CONCLUSION: Corticotomy-accelerated tooth movement is a promising technique that has many applications in orthodontic treatment of adults as it helps overcome many of the current limitations of this treatment. The enzymatic activity signifies osteoclastic and osteoblastic activities, so ALP and AST from the saliva and GCF may potentially be used as biomarkers for monitoring corticotomy-assisted OTM.
Impact of sites versus number of metastases on survival of patients with organ metastasis from newly diagnosed cervical cancer

Objective The aim of this study was to investigate the potential associations of the sites and the number of specific metastases with survival in patients newly diagnosed with cervical cancer. Methods Medical records of patients with organ metastases of newly diagnosed cervical cancer at Zhejiang Cancer Hospital from October 2006 to December 2016 were reviewed retrospectively. Survival times were compared using the Kaplan-Meier method. Variables associated with survival were identified using univariate and multivariate Cox proportional hazards models. Results A total of 99 patients with newly diagnosed organ metastatic cervical cancer were identified. Median follow-up was 11.6 months (range, 0.5–114.7 months). Median overall survival (OS) time was 11.7 months from diagnosis, with 1, 2, and 5-year OS rates of 48.2%, 22.8%, and 12.6%, respectively. The most common site of organ metastasis was bone (36.8%), followed by lung (32.8%) and liver (24%). In univariate analysis, OS rates were better for bone metastasis than visceral metastasis (P=0.013), oligometastasis than non-oligometastasis (P=0.003) and single organ metastasis than multiple organ metastases (P=0.016), while that for liver metastasis was poorer than non-liver metastases (P<0.001). In multivariate analysis, liver metastasis (hazard ratio [HR] =4.02; 95% confidence interval [CI], 1.15-14.05, P=0.029) was significantly and independently related to poor overall survival. Conclusion Our data revealed the site of metastasis is associated with overall survival of patients with newly diagnosed organ metastatic cervical cancer, with liver metastasis signifying particularly poor overall survival. Individualized treatments should be administered to patients depending on the specific metastatic sites.