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To compare the effect of ultrasound (US)-guided dry needling (DN) with traditional DN in the treatment of pain and dysfunction for patients with knee osteoarthritis (KOA). A double-blind, randomized controlled trial. Eighty-four participants (61.26±5.57 years) completed the study. G1 achieved significant improvement in VAS at 8 weeks compared to G2 and G3 (G1 vs. G2: MD = -15.61, 95% CI [-25.49, -5.51], p = 0.001; G1 vs. G3: MD = -19.90, 95% CI [-29.71, -10.08], p< 0.001). G1 achieved significant improvement in KOOS-pain at 8 weeks compared to G2 and G3 (G1 vs. G2: MD = 9.76, 95% CI [2.38, 17.14], p = 0.006; G1 vs. G3: MD = 9.48, 95% CI [2.31, 16.66], p = 0.010). KOOS-symptoms and KOOS-QoL were not statistically significant between groups. G2 had no significant difference of the perceptions as G1 with p = 0.128. G2 were successfully blinded to placebo US-guided DN. US-guided DN with exercise therapy may be more effective than traditional DN with exercise therapy or exercise therapy alone in reduce pain of KOA.

ABSTRACT In this article we introduce the concept of inverse probability of treatment weighting (IPTW) and describe how this method can be applied to adjust for measured confounding in observational research, illustrated by a clinical example from nephrology. IPTW involves two main steps. First, the probability—or propensity—of being exposed to the risk factor or intervention of interest is calculated, given an individual’s characteristics (i.e. propensity score). Second, weights are calculated as the inverse of the propensity score. The application of these weights to the study population creates a pseudopopulation in which confounders are equally distributed across exposed and unexposed groups. We also elaborate on how weighting can be applied in longitudinal studies to deal with informative censoring and time-dependent confounding in the setting of treatment-confounder feedback.

Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS 2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS 2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure. Topological superconductors are potentially important for future quantum computation, but they are very rare in nature. Here, the authors observe topological surface states acquiring a nodeless superconducting gap with similar magnitude as that of the bulk states in 2M-WS 2 , suggesting an intrinsic topological superconductor.

High rotational speed friction stir welding (FSW) was successfully employed to weld 6061-T6 aluminum alloy thin plates. The effect of high rotational speed and fast transverse speed on temperature distribution, microstructure evolution, and tensile properties of friction stir welded 6061-T6 joints was investigated in detail. The high rotational speed with fast transverse speed had a significant influence on the peak temperature in the nugget zone (NZ). Increasing the rotational speed and decreasing the transverse speed could obviously improve the peak temperature in the NZ, but exhibit little effect on the heat-affected zone under high rotational speed FSW. The NZ was characterized as a significant refinement of the equiaxed grain. The number of precipitates, subgrains, and low angle grain boundaries in the NZ of high rotational speed FSW joint increased significantly due to moderate heat input and strain rate. The weld zone was seriously softened at low rotational speed, whereas it was alleviated at high rotational speed and was affected slightly by rotational speed and transverse speed. The excellent mechanical properties of the friction stir welded 6061-T6 joints were obtained at a combination of high rotational speed and fast transverse speed. The maximum tensile strength reached 301.8 MPa, 85.8% of the base material.

Background Dentists with a dentist parent are often assumed to have inherent career advantages. Despite the high prevalence of these “second-generation” dentists, little research has examined whether they are actually happier than others. This study investigated life satisfaction among dentists with a dentist parent, compared to those with a physician parent or non-physician/dentist parents. Methods A cross-sectional survey was conducted among Taiwanese dentists, assessing their life satisfaction using the 5-item Satisfaction With Life Scale (SWLS), along with sociodemographic and career-related factors. Descriptive statistics and multiple linear regression analyses were performed to identify factors associated with SWLS scores. Results Among 1,170 respondents (mean age = 43.5 years, SD = 12.0; 46.5% female), the prevalence of young dentists with at least one dentist parent increased from 2 to 10% over the past two decades, whereas the prevalence of dentists with a physician parent remained around 10%. Multivariable analysis revealed that dentists with a dentist parent reported lower mean SWLS scores (β = -0.245; p  = 0.015) after accounting for potential confounders. When the items of the SWLS scale were analyzed individually, dentists with a dentist parent had similar current life satisfaction, but lower past life satisfaction (β = -0.541; p  < 0.001) than those without physician/dentist parents. Among dentists who ranked in the top 25% of their class, those with a dentist parent reported the lowest mean SWLS scores. In contrast, dentists with a physician parent did not experience the same decline in life satisfaction observed among second-generation dentists. Conclusion Although the small sample size of second-generation dentists limits the strength of inferences, these findings highlight the growing prevalence of second-generation dentists in Taiwan, their regret over past choices, and the potential challenges unique to this group. Understanding the pressures faced by second-generation dentists may inform strategies to enhance their professional fulfillment and overall well-being.

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.

SIRT4 is well-known for its deacetylase activity in energy metabolism, but little is known about its roles in carcinogenesis. We demonstrated that SIRT4 was decreased in 70 out of 133 non-small cell lung cancer (NSCLC) cases by immunohistochemical staining and localized in the mitochondria using confocal microscopy. Low levels of SIRT4 expression was correlated with tumor node metastasis (TNM) stage, histological type of tumor (adenocarcinoma), lymph nodal status, Ki-67 (proliferation index) and poor overall survival. We also studied the biological role of SIRT4 in lung cancer cell lines transfected with SIRT4 plasmid or SIRT4-siRNA. SIRT4 inhibited lung cancer cell proliferation, blocked the cell cycle and repressed cell invasion and migration. Mitochondrial dynamics has been implicated in malignant properties of cells, particularly metastasis that is the major cause of death in patients diagnosed with cancer including lung cancer. This is the first study to identify an association between SIRT4 expression and decreased mitochondrial fission, which was driven by Drp1. SIRT4 inhibited Drp1 phosphorylation and weakened Drp1 recruitment to the mitochondrial membrane via an interaction with Fis-1. SIRT4 expression was lower in nodal metastatic tumor samples than their corresponding primary tumors, and cases with low expression of SIRT4 tended to have high p-Drp1 labeling. Also, MEK/ERK activity appeared to be hampered by SIRT4 expression, which may have implications for cells’ invasive capacities. In conclusion, our findings suggest that SIRT4 functions as an important antitumor protein in NSCLC, and should be investigated further with respect to future anticancer strategies.

Chronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD and atrial fibrillation and outcomes. We included 12,394 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2018 for an out-patient visit (Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding, ischemic stroke or mortality were calculated with Cox proportional hazard analyses. Presence of interaction between AF and CKD was examined by calculating the relative excess risk due to interaction (RERI), the attributable proportion (AP) due to interaction and the synergy index (S). Of the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and 325 patients had both AF and CKD. Patients with both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold (95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6) increased mortality risk after adjustment as compared with subjects without atrial fibrillation and CKD. We did not find interaction between AF and CKD for bleeding and mortality. However, we found interaction between AF and CKD for ischemic stroke risk (RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32)). AF and CKD are both associated with bleeding, ischemic stroke and mortality. There is a positive interaction between AF and CKD for ischemic stroke risk, but not for bleeding or mortality.

In this work, we have studied the non-Hermitian nonlinear Landau–Zener–Stückelberg–Majorana (LZSM) interferometry in a non-Hermitian N -body interacting boson system in which the non-Hermiticity is from the nonreciprocal tunnelings between the bosons. By using the mean-field approximation and projective Hilbert space, the effect of nonreciprocity and nonlinearity on the energy spectrum, the dynamics, and the formation of the interference fringes have been studied. The different symmetries and the impact of the two different types of reciprocity, i.e. the in-phase tunneling and anti-phase tunneling, on the energy spectrum and the phase transition between the Josephson oscillations and the self-trapping have been investigated. For the LZSM interferometry, the strength of the nonreciprocity is found to take an essential role in the population of the projective state and the strengths of the interference patterns in the projective space. While the conditions of destructive and constructive interference under the weak-coupling approximation still only depend on the strength of nonlinearity. Our result provides an application of the nonlinear non-Hermitian LZSM interferometry in studying the parameters of a two-level system which related to the nonlinearity and the non-Hermiticity.

AbstractObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort study.SettingNational Swedish Renal Registry of patients referred to nephrologists.ParticipantsPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.Main outcome measuresThe strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m2 in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2 (eGFR6-7) was taken as the reference.ResultsAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR10-14v eGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10v eGFR5-7), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.ConclusionsVery early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.