The timing and cause of glacial activity during the last glacial in central Tibet based on Be-10 surface exposure dating east of Mount Jaggang, the Xainza range

Mountain glaciers are sensitive to climate change, and can provide valuable information for inferring former climates on the Tibetan Plateau (TP). The increasing glacial chronologies indicate that the timing of the local Last Glacial Maximum (LGM) recorded across the TP is asynchronous, implying different local influences of the mid-latitude westerlies and Asian Summer Monsoon in triggering glacier advances. However, the well-dated sites are still too few, especially in the transition zone between regions controlled by the two climate systems. Here we present detailed last glacial chronologies for the Mount Jaggang area, in the Xainza range, central Tibet, with forty-three apparent Be-10 exposure-ages ranging from 12.4 +/- 0.8 ka to 61.9 +/- 3.8 ka. These exposure-ages indicate that at least seven glacial episodes occurred during the last glacial cycle east of Mount Jaggang. These include: a local LGM that occurred at similar to 61.9 +/- 3.8 ka, possibly corresponding to Marine Isotope Stage 4 (MIS 4); subsequent glacial advances at similar to 43.2 +/- 2.6 ka and similar to 35.1 +/- 2.1 ka during MIS 3; one glacial re-advance/standstill at MIS3/2 transition (similar to 29.8 +/- 1.8 ka); and three glacial re-advances/standstills that occurred following MIS 3 at similar to 27.9 +/- 1.7 ka, similar to 21.8 +/- 13 ka, and similar to 15.1 +/- 0.9 ka. The timing of these glacial activities is roughly in agreement with North Atlantic millennial-scale climate oscillations (Heinrich events), suggesting the potential correlations between these abrupt climate changes and glacial fluctuations in the Mount Jaggang area. The successively reduced glacial extent might have resulted from an overall decrease in Asian Summer Monsoon intensity over this timeframe. (C) 2018 Elsevier Ltd. All rights reserved

SA-Solver: Stochastic Adams Solver for Fast Sampling of Diffusion Models

Diffusion Probabilistic Models (DPMs) have achieved considerable success in generation tasks. As sampling from DPMs is equivalent to solving diffusion SDE or ODE which is time-consuming, numerous fast sampling methods built upon improved differential equation solvers are proposed. The majority of such techniques consider solving the diffusion ODE due to its superior efficiency. However, stochastic sampling could offer additional advantages in generating diverse and high-quality data. In this work, we engage in a comprehensive analysis of stochastic sampling from two aspects: variance-controlled diffusion SDE and linear multi-step SDE solver. Based on our analysis, we propose SA-Solver, which is an improved efficient stochastic Adams method for solving diffusion SDE to generate data with high quality. Our experiments show that SA-Solver achieves: 1) improved or comparable performance compared with the existing state-of-the-art sampling methods for few-step sampling; 2) SOTA FID scores on substantial benchmark datasets under a suitable number of function evaluations (NFEs)

Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs

In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends

HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis

Nasopharyngeal carcinoma (NPC), as one of the most prevalent malignancies in the head and neck region, still lacks a complete understanding of its pathogenesis. Presently, radiotherapy, concurrent chemoradiotherapy, and targeted therapy stand as the primary modalities for treating NPC. With advancements in medicine, the cure rates for nasopharyngeal carcinoma have been steadily increasing. Nevertheless, recurrence and metastasis persist as the primary reasons for treatment failure. Consequently, a profound exploration of the molecular mechanisms underlying the occurrence and progression of nasopharyngeal carcinoma, along with the exploration of corresponding therapeutic approaches, becomes particularly imperative in the quest for comprehensive solutions to combat this disease. High mobility group AT-hook 2 (HMGA2) is a pivotal protein capable of altering chromatin structure, regulating gene expression, and influencing transcriptional activity. In the realm of cancer research, HMGA2 exhibits widespread dysregulation, playing a crucial role in nearly all malignant tumors. It is implicated in various tumorigenic processes, including cell cycle regulation, cell proliferation, epithelial-mesenchymal transition, angiogenesis, tumor invasion, metastasis, and drug resistance. Additionally, HMGA2 serves as a molecular marker and an independent prognostic factor in certain malignancies. Recent studies have increasingly unveiled the critical role of HMGA2 in nasopharyngeal carcinoma (NPC), particularly in promoting malignant progression, correlating with tumor resistance, and serving as an independent adverse prognostic factor. This review focuses on elucidating the oncogenic role of HMGA2 in NPC, suggesting its potential association with chemotherapy resistance in NPC, and proposing its candidacy as an independent factor in nasopharyngeal carcinoma prognosis assessment

Comparison of the asymmetries in muscle mass, biomechanical property and muscle activation asymmetry of quadriceps femoris between patients with unilateral and bilateral knee osteoarthritis

Background: More and more attention has been paid to the research of muscle mass and muscle quality of quadriceps femoris (QF) in knee osteoarthritis (KOA). This study aimed to explore the asymmetric changes of muscle mass, biomechanical property and muscle activation in the inter-limbs QF of KOA patients, and tried to provide a novel insight for the evaluation, prevention and treatment of KOA.Methods: A total of 56 Participants with unilateral or bilateral KOA were included in this study: 30 patients with unilateral pain and 26 patients with bilateral pain were assigned to the bilateral group (BG) and unilateral group (UG), respectively. The symptom severity of bilateral lower limbs was evaluated by visual analogue scale, and the relatively serious leg (RSL) and relatively moderate leg (RML) were classified. The thickness of rectus femoris (RF), vastus intermedius (VI), vastus medialis (VM) and vastus lateralis (VL) were measured by ultrasound. The Shear wave elastography (SWE) techniqie was used to measure the shear modulus of RF, VM and VL. Surface electromyography (sEMG) was used to assess the root mean square (RMS) of the RF, VM, and VL during straight leg raising in a sitting position and squatting task. We calculated the asymmetry indexes of inter-limbs for the corresponding indices of the measured muscles.Result: Thickness of RF, VI and VL of RSL was lower than those on RML (p < 0.05), and thickness of VM was lower more significant (p < 0.01). Thickness of RF, VI and VL of RSL was also lower than those of RML in BG (p < 0.05), however, there was no significant difference in VM thickness (p > 0.05). There were no significant difference in Asymmetry indexes of all measured muscle thickness between the two groups (p > 0.05). The Shear modulus of RF, VM, and VL in the RML of UG and BG was higher than those in the RSL (p < 0.05). In sitting and straight leg raising task, the RMS of RF, VM and VL in RML were higher than those in RSL, UG and BG both showed this trend (p < 0.05). About squatting task, in UG, the RMS of the three muscles in RML of patients were also higher than those in the RSL (p < 0.05). However, the difference was not significant in BG (p > 0.05). In the straight leg raising task, the asymmetry indexes of RMS in RF, VM, and VL of both the two groups were positively correlated with VAS scores (p < 0.05).Conclusion: The muscle thickness, shear modulus and muscle activation electromyography of QF in RML were higher than those of RSL in unilateral KOA patients. The VM of RML in bilateral KOA patients may show muscle thickness degeneration earlier, which is closer to the VM of RSL. The shear modulus of RF, VM, and VL were higher on the RML side during the single-leg task, but there may be passive compensation for muscle activation in both lower limbs during the bipedal task. In conclusion, there is a general asymmetry of QF muscle mass, biomechanics Characteristic and performance in patients with KOA, which may provide new ideas for the assessment, treatment and rehabilitation of the disease

Reliability of foot posture index (FPI-6) for evaluating foot posture in patients with knee osteoarthritis

Objective: To determine the reliability of FPI-6 in the assessment of foot posture in patients with knee osteoarthritis (KOA).Methods: Thirty volunteers with KOA (23 females, 7 males) were included in this study, assessed by two raters and at three different moments. Inter-rater and test-retest reliability were assessed with Cohen’s Weighted Kappa (Kw) and Intraclass Correlation Coefficient (ICC). Bland-Altman plots and respective 95% limits of agreement (LOA) were used to assess both inter-rater and test-retest agreement and identify systematic bias. Moreover, the internal consistency of FPI-6 was assessed by Spearman’s correlation coefficient.Results: FPI-6 total score showed a substantial inter-rater (Kw = .66) and test-retest reliability (Kw = .72). The six items of FPI-6 demonstrated inter-rater and test-retest reliability varying from fair to substantial (Kw = .33 to .76 and Kw = .40 to .78, respectively). Bland-Altman plots and respective 95% LOA indicated that there appeared no systematic bias and the acceptable agreement of FPI-6 total score for inter-rater and test-retest was excellent. There was a statistically significant positive correlation between each item and the total score of FPI-6, which indicated that FPI-6 had good internal consistency.Conclusion: In conclusion, the reliability of FPI-6 total score and the six items of FPI-6 were fair to substantial. The results can provide a reliable way for clinicians and researchers to implement the assessment of foot posture in patients with KOA

Preoperative Strength Training for Clinical Outcomes Before and After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

BackgroundThere is an increasing interest in preoperative strength training for promoting post-operative rehabilitation, but the effectiveness of preoperative strength training for clinical outcomes after total knee arthroplasty (TKA) remains controversial.ObjectiveThis study aims to systematically evaluate the effect of preoperative strength training on clinical outcomes before and after TKA.MethodsWe systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE databases from the inception to November 17, 2021. The meta-analysis was performed to evaluate the effects of preoperative strength training on clinical outcomes before and after TKA.ResultsSeven randomized controlled trials (RCTs) were included (n = 306). Immediately before TKA, the pooled results showed significant improvements in pain, knee function, functional ability, stiffness, and physical function in the strength training group compared with the control group, but not in strength (quadriceps), ROM, and WOMAC (total). Compared with the control group, the results indicated strength training had a statistically significant improvement in post-operative knee function, ROM, and functional ability at less than 1 month and 3 months, and had a statistically significant improvement in post-operative strength (quadriceps), stiffness, and WOMAC (total) at 3 months, and had a statistically significant improvement in post-operative pain at 6 months. However, the results indicated strength training had no statistically significant improvement in post-operative strength (quadriceps) at less than 1 month, 6, and 12 months, had no statistically significant improvement in post-operative pain at less than 1 month, 3, and 12 months, had no statistically significant improvement in post-operative knee function at 6 and 12 months, and had no statistically significant improvement in post-operative physical function at 3 months.ConclusionsPreoperative strength training may be beneficial to early rehabilitation after TKA, but the long-term efficacy needs to be further determined. At the same time, more caution should be exercised when interpreting the clinical efficacy of preoperative strength training for TKA

A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor

Background: Simmitecan is a potent inhibitor of topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs.Methods: Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred.Results: A total of 41 patients were enrolled, with a median age of 55 (range 29–69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one colorectal cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively.Conclusion: This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study

Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas.Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association.Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III.Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs