SGLT2 inhibitor plus DPP‐4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta‐analysis

To assess the efficacy and safety of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors plus a dipeptidyl peptidase‐4 (DPP‐4) inhibitor in patients with type 2 diabetes mellitus (T2DM), we performed a systematic review and meta‐analysis of 14 randomized controlled trials (RCTs) involving 4828 patients. Compared with a DPP‐4 inhibitor, SGLT2 inhibitor/DPP‐4 inhibitor combination therapy was significantly associated with a decrease in glycaemic control (HbA1c, −0.71%; fasting plasma glucose [FPG], −25.62 mg/dL; postprandial plasma glucose, −44.00 mg/dL), body weight (−2.05 kg) and systolic blood pressure (−5.90 mm Hg), but an increase in total cholesterol (TC) of 3.24%, high‐density lipoprotein of 6.15% and low‐density lipoprotein of 2.55%. Adding a DPP‐4 inhibitor to an SGLT2 inhibitor could reduce HbA1c by −0.31%, FPG by −8.94 mg/dL, TC by −1.48% and triglycerides by −3.25%. Interestingly, low doses of an SGLT2 inhibitor in the combination has similar or even better efficacy in some aspects than high doses. Similar adverse events were observed for the combination therapy, with the exception of genital infection vs DPP‐4 inhibitor (risk ratio [RR], 5.31) and consistent genital infection vs an SGLT2 inhibitor (RR, 0.61). Further studies are warranted to confirm these results

Effect of Sodium–Glucose Cotransporter 2 Inhibitors on Diabetic Ketoacidosis Among Patients With Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials

SCI(E)[email protected]

Galaxy stellar and total mass estimation using machine learning

Conventional galaxy mass estimation methods suffer from model assumptions and degeneracies. Machine learning (ML), which reduces the reliance on such assumptions, can be used to determine how well present-day observations can yield predictions for the distributions of stellar and dark matter. In this work, we use a general sample of galaxies from the TNG100 simulation to investigate the ability of multibranch convolutional neural network (CNN) based ML methods to predict the central (i.e. within 1−2 effective radii) stellar and total masses, and the stellar mass-to-light ratio (M*/L). These models take galaxy images and spatially resolved mean velocity and velocity dispersion maps as inputs. Such CNN-based models can, in general, break the degeneracy between baryonic and dark matter in the sense that the model can make reliable predictions on the individual contributions of each component. For example, with r-band images and two galaxy kinematic maps as inputs, our model predicting M*/L has a prediction uncertainty of 0.04 dex. Moreover, to investigate which (global) features significantly contribute to the correct predictions of the properties above, we utilize a gradient-boosting machine. We find that galaxy luminosity dominates the prediction of all masses in the central regions, with stellar velocity dispersion coming next. We also investigate the main contributing features when predicting stellar and dark matter mass fractions (f*, fDM) and the dark matter mass MDM, and discuss the underlying astrophysics

Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials

Aim To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted

The neural dynamic mechanisms of asymmetric switch costs in a combined Stroop-task-switching paradigm

Switch costs have been constantly found asymmetrical when switching between two tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and recorded electroencephalographic (EEG) signals to explore the neural mechanism underlying the phenomenon of asymmetrical switch costs. The results revealed that a fronto-central N2 component demonstrated greater negativity in word switch (cW) trials relative to word repeat (wW) trials, and both First P3 and P3b components over the parieto-central region exhibited greater positivity in color switch (wC) trials relative to color repeat (cC) trials, whereas a contrasting switch-related fronto-central SP effect was found to have an opposite pattern for each task. Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9-11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11-13 Hz) modulation was exclusively found in the color task. These results provide evidence for dissociable neural processes, which are related to inhibitory control and endogenous control, contributing to the generation of asymmetrical switch costs

Enhancing Faraday and Kerr rotations based on toroidal dipole mode in an all-dielectric magneto-optical metasurface

The magneto-optical Faraday and Kerr effects are widely used in modern optical devices. In this letter, we propose an all-dielectric metasurface composed of perforated magneto-optical thin films, which can support the highly confined toroidal dipole resonance and provide full overlap between the localized electromagnetic field and the thin film, and consequently enhance the magneto-optical effects to an unprecedented degree. The numerical results based on finite element method show that the Faraday and Kerr rotations can reach -13.59${\deg}$ and 8.19${\deg}$ in the vicinity of toroidal dipole resonance, which are 21.2 and 32.8 times stronger than those in the equivalent thickness of thin films, respectively. In addition, we design an environment refractive index sensor based on the resonantly enhanced Faraday and Kerr rotations, with sensitivities of 62.96 nm/RIU and 73.16 nm/RIU, and the corresponding maximum figures of merit 132.22${\deg}$/RIU and 429.45${\deg}$/RIU, respectively. This work provides a new strategy for enhancing the magneto-optical effects at nanoscale, and paves the way for the research and development of magneto-optical metadevices such as sensors, memories, and circuits

Familial multinodular goiter syndrome with papillary thyroid carcinomas: mutational analysis of the associated genes in 5 cases from 1 Chinese family

Background: Familial papillary thyroid cancer (fPTC) is recognized as a distinct entity only recently and no fPTC predisposing genes have been identified. Several potential regions and susceptibility loci for sporadic PTC have been reported. We aimed to evaluate the role of the reported susceptibility loci and potential risk genomic region in a Chinese familial multinodular goiter (fMNG) with PTC family. Methods: We sequenced the related risk genomic regions and analyzed the known PTC susceptibility loci in the Chinese family members who consented to join the study. These loci included (1) the point mutations of the BRAF and RET; (2) the possible susceptibility loci to sporadic PTC; and (3) the suggested potential fMNG syndrome with PTC risk region. Results: The members showed no mutations in the common susceptible BRAF and RET genomic region, although contained several different heterozygous alleles in the RET introns. All the members were homozygous for PTC risk alleles of rs966423 (C) at chromosome 2q35, rs2910164 (C) at chromosome 5q24 and rs2439302 (G) at chromosome 8p12; while carried no risk allele of rs4733616 (T) at chromosome 8q24, rs965513 (A) or rs1867277 (A) at chromosome 9q22 which were associated with radiation-related PTC. The frequency of the risk allele of rs944289 (T) but not that of rs116909374 (T) at chromosome 14q13 was increased in the MNG or PTC family members. Conclusions: Our work provided additional evidence to the genetic predisposition to a Chinese familial form of MNG with PTC. The family members carried quite a few risk alleles found in sporadic PTC; particularly, homozygous rs944289 (T) at chromosome 14q13 which was previously shown to be linked to a form of fMNG with PTC. Moreover, the genetic determinants of radiation-related PTC were not presented in this family

PPE38 of Mycobacterium marinum Triggers the Cross-Talk of Multiple Pathways Involved in the Host Response, As Revealed by Subcellular Quantitative Proteomics

The PE/PPE family of proteins which are in high abundance in pathogenic species such as Mycobacterium tuberculosis and M. marinum, play the critical role in generating antigenic variation and evasion of host immune responses. However, little is known about their functional roles in mycobacterial pathogenesis. Previously, we found that PPE38 is associated with the virulence of mycobacteria, presumably by modulating the host immune response. To clarify the link between PPE38 and host response, we employed a subcellular, amino acid-coded mass tagging (AACT)/SILAC-based quantitative proteomic approach to determine the proteome changes during host response to M. marinum PPE38. As a result, 291 or 290 proteins were found respectively to be up- or down-regulated in the nucleus. Meanwhile, 576 upregulated and 272 downregulated proteins were respectively detected in the cytosol. The data of quantitative proteomic changes and concurrent biological validations revealed that M. marinum PPE38 could trigger extensive inflammatory responses in macrophages, probably through interacting with toll-like receptor 2 (TLR2). We also found that PPE38 may arrest MHC-1 processing and presentation in infected macrophages. Using bioinformatics tools to analyze global changes in the host proteome, we obtained a PPE38-respondor network involved in various transcriptional factors (TFs) and TF-associated proteins. The results of our systems investigation now indicate that there is cross-talk involving a broad range of diverse biological pathways/processes that coordinate the host response to M. marinum PPE38

The effectiveness of exercise on the symptoms in breast cancer patients undergoing adjuvant treatment: an umbrella review of systematic reviews and meta-analyses

BackgroundExercise has the potential to reduce symptoms for breast cancer patients during adjuvant treatment, and high-quality systematic reviews are essential for guiding clinical practice. The objective of this umbrella review is to examine current research evidence concerning the effectiveness of exercise on symptom management in breast cancer patients undergoing adjuvant treatment.MethodsAn umbrella review was conducted. We searched for eligible systematic reviews through 11 databases until August 13rd, 2023. Two authors independently screened titles and abstracts, assessing the full-text studies based on inclusion criteria. We used AMSTAR-2 to appraise the quality of the meta-analyses. The results would be presented with narrative summaries if the replication rate of the original study for a symptom was higher than 5% (calculated via the Corrected Covered Area, CCA). The protocol was documented in the PROSPERO registry (CRD42023403990).ResultsOf the 807 systematic reviews identified, 15 met the inclusion criteria, and 7 symptoms were the main focus. The main form of exercise mentioned was aerobic combined resistance exercise. The results of the quality assessment were mostly critically low (10/15). The repetition rate calculated by CCA showed moderate to very high repetition rates (10% to 18.6%). The findings of the included reviews indicated that the effects of exercise on relieving symptoms during breast cancer adjuvant treatment were mixed.ConclusionsResearch is still needed to confirm the majority of studies’ recommendations for exercise during adjuvant treatment for breast cancer patients, as it is crucial for managing symptoms in the rehabilitation process. To increase the efficiency of exercise in symptom management, future studies may focus more on the application of bridge symptoms, symptom networks, and ecological instantaneous assessment