Enhanced cancer therapy with cold-controlled drug release and photothermal warming enabled by one nanoplatform

Stimuli-responsive nanoparticles hold great promise for drug delivery to improve the safety and efficacy of cancer therapy. One of the most investigated stimuli-responsive strategies is to induce drug release by heating with laser, ultrasound, or electromagnetic field. More recently, cryosurgery (also called cryotherapy and cryoablation), destruction of diseased tissues by first cooling/freezing and then warming back, has been used to treat various diseases including cancer in the clinic. Here we developed a cold-responsive nanoparticle for controlled drug release as a result of the irreversible disassembly of the nanoparticle when cooled to below ∼10 °C. Furthermore, this nanoparticle can be used to generate localized heating under near infrared (NIR) laser irradiation, which can facilitate the warming process after cooling/freezing during cryosurgery. Indeed, the combination of this cold-responsive nanoparticle with ice cooling and NIR laser irradiation can greatly augment cancer destruction both in vitro and in vivo with no evident systemic toxicity

Dynamic Rheological Studies of Poly(p-phenyleneterephthalamide) and Carbon Nanotube Blends in Sulfuric Acid

We have studied the dynamic scanning of liquid-crystalline (LC) poly(p-phenyleneterephthalamide) sulfuric acid (PPTA-H2SO4) solution, and its blend with single-walled carbon nanotubes (SWNTs), by using a flat plate rotational rheometer. The effects of weight concentration and molecular weight of PPTA, as well as operating temperature, on dynamic viscoelasticity of the PPTA-H2SO4 LC solution system are discussed. The transition from a biphasic system to a single-phase LC occurs in the weight concentration range of SWNTs from 0.1% to 0.2%, in which complex viscosity reaches the maximum at 0.2 wt% and the minimum at 0.1 wt%, respectively, of SWNTs. With increasing SWNT weight concentration, the endothermic peak temperature increases from 73.6 to 79.9 °C. The PPTA/SWNT/H2SO4 solution is in its plateau zone and storage modulus (G′) is a dominant factor within the frequency (ω) range of 0.1–10 rad/s. As ω increases, the G′ rises slightly, in direct proportion to the ω. The loss modulus (G″) does not rise as a function of ω when ω < 1 s−1, then when ω > 1 s−1 G″ increases faster than G′, yet not in any proportion to the ω

Deciphering Spatio-Temporal Graph Forecasting: A Causal Lens and Treatment

Spatio-Temporal Graph (STG) forecasting is a fundamental task in many real-world applications. Spatio-Temporal Graph Neural Networks have emerged as the most popular method for STG forecasting, but they often struggle with temporal out-of-distribution (OoD) issues and dynamic spatial causation. In this paper, we propose a novel framework called CaST to tackle these two challenges via causal treatments. Concretely, leveraging a causal lens, we first build a structural causal model to decipher the data generation process of STGs. To handle the temporal OoD issue, we employ the back-door adjustment by a novel disentanglement block to separate invariant parts and temporal environments from input data. Moreover, we utilize the front-door adjustment and adopt the Hodge-Laplacian operator for edge-level convolution to model the ripple effect of causation. Experiments results on three real-world datasets demonstrate the effectiveness and practicality of CaST, which consistently outperforms existing methods with good interpretability.Comment: To appear at NeurIPS 202

Predicting Transition Temperature of Superconductors with Graph Neural Networks

Predicting high temperature superconductors has long been a great challenge. The difficulty lies in how to predict the transition temperature (Tc) of superconductors. Although recent progress in material informatics has led to a number of machine learning models predicting Tc, prevailing models have not shown adequate generalization ability and physical rationality to find new high temperature superconductors, yet. In this work, a bond sensitive graph neural network (BSGNN) was developed to predict the Tc of various superconductors. In BSGNN, communicative message passing and graph attention methods were utilized to enhance the model's ability to process bonding and interaction information in the crystal lattice, which is crucial for the superconductivity. Consequently, our results revealed the relevance between chemical bond attributes and Tc. It indicates that shorter bond length is favored by high Tc. Meanwhile, some specific chemical elements that have relatively large van der Waals radius is favored by high Tc. It gives a convenient guidance for searching high temperature superconductors in materials database, by ruling out the materials that could never have high Tc

Percutaneous transforaminal endoscopic surgery combined with mini-incision OLIF and anterolateral screws rod fixation vs. MIS-TLIF for surgical treatment of single-level lumbar spondylolisthesis

ObjectiveOblique lumbar interbody fusion (OLIF) has been used to treat lumbar spine spondylolisthesis. However, it usually needs posterior pedicle screws fixation for biomechanical stability and possible posterior direct decompression for relieving neurologic symptoms. We use percutaneous transforaminal endoscopic surgery (PTES) combined with mini-incision OLIF and anterolateral screws rod fixation for surgical treatment of lumbar spondylolisthesis. The purpose of study is to evaluate the feasibility, efficacy, and safety of this method compared with minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF).MethodsFrom July 2016 to May 2018, 65 patients of lumbar spondylolisthesis (L2–4) with neurologic symptoms were treated using PTES combined with mini-incision OLIF and anterolateral screws rod fixation (31 cases, group A) or MIS-TLIF (34 cases, group B) in this study. Operative duration, blood loss, incision length, fluoroscopy frequency, and hospital stay are compared. Preoperative and postoperative visual analog scale (VAS) pain scores of back and legs, Oswestry disability index (ODI), intervertebral space height, lumbar lordotic angle, operative segmental lordotic angle, and complications are recorded. The fusion status is assessed according to Bridwell's fusion grades.ResultsThe VAS score of back and leg pain and ODI significantly dropped after surgery in both groups (p &lt; 0.001). There was no statistical difference of back and leg VAS score and ODI between two groups except that back VAS scores in group A were significantly lower than that of group B immediately after surgery (p = 0.000). Group A had significantly more intervertebral space height and operative segmental lordotic angle than group B postoperatively (p = 0.022, p = 0.002). Twenty-three segments (74.2%) were grade I and 8 segments (25.8%) were grade II in group A; 20 segments (58.8%) were grade I and 14 segments (41.2%) were grade II in group B at a 2-year follow-up (p = 0.194). No difference was observed in the complication rate between the two groups (6.5% vs. 5.9%, p = 0.924).ConclusionThe long-term clinical efficacy and complication rates of both groups are comparable. PTES combined with mini-incision OLIF and anterolateral screws rod fixation is a good choice of minimally invasive surgery for lumbar spondylolisthesis, which hardly destroys the paraspinal muscles and bone structures

Editorial: Epidemiology and clinical researches on neuropsychiatric disorders in aging

 With the rising aging population in a global range, related neuropsychiatric disorders such as depression and dementia, have emerged and caused a tremendous disease burden. Over the past decades, many risk factors have been identified (1–12), and advances have been made in developing prevention and intervention strategies. However, there still exist challenges to be addressed. These challenges include but are not limited to early detection and prediction of neuropsychiatric disorders, comorbidities of both neuropsychiatric and non-neuropsychiatric aspects, identifying novel indicators for disease progression and prognosis, as well as investigating potential mediating mechanisms. Facing unprecedented challenges, we launched this Research Topic to promote healthy aging and longevity from the neuropsychiatric perspective, via collaboration from a number of professional disciplines. </p

How to predict the culprit segment in percutaneous transforaminal endoscopic surgery under local anesthesia for surgical treatment of lumbar degenerative diseases? Radiologic images or clinical symptoms

ObjectivePercutaneous transforaminal endoscopic surgery (PTES) is a novel, minimally invasive technique used to treat lumbar degenerative diseases (LDDs). PTES under local anesthesia was performed to treat the culprit segment of LDDs predicted by radiologic images or clinical symptoms, and the efficacy, security, and feasibility were evaluated.MethodsEighty-seven cases of LDDs with nerve root symptoms, which were not consistent with lumbar degenerative levels and degrees on MRI and CT, were treated with PTES under local anesthesia in a day surgery ward from January 2015 to December 2019. Forty-two patients, whose culprit segments were predicted by radiologic images, were included in group A. The other 45 patients, whose culprit segments were predicted by clinical symptoms, were included in group B. Leg pain VAS and ODI scores before and after PTES were recorded. The outcome was defined according to the MacNab grade at the 2-year follow-up. Postoperative complications were recorded.ResultsIn group A, 2 patients underwent PTES for one segment, 37 patients underwent PTES for two segments, and 3 patients underwent PTES for three segments. One of the one-segment PTES patients had no relief from symptoms and underwent another PTES for other culprit segments 3 months after surgery. In group B, 44 of 45 patients were treated using PTES for one segment and 1 patient was treated for two segments. Group B showed significantly less operative duration, less blood loss, and less fluoroscopy frequency than group A (p &lt; 0.001). The leg pain VAS score and the ODI score significantly decreased after the operation in both groups (p &lt; 0.001), and the excellent and good rates were 97.6% (41/42) in group A and 100% (45/45) in group B at the 2-year follow-up. The leg pain VAS score of group B was significantly lower than that of group A immediately and 1 week, 1 month, 2 months, and 3 months after surgery (p &lt; 0.001). There was no statistical difference in ODI scores and the excellent and good rates between the two groups. No complications, such as wound infection or permanent nerve injury, were observed.ConclusionIt is much more accurate to predict the culprit segment according to clinical symptoms than radiologic images in PTES under local anesthesia for surgical treatment of LDDs

Factors influencing the quality of clinical trials on traditional Chinese medicine— Qualitative interviews with trial auditors, clinicians and academic researchers

Background: As clinical trials evaluating the efficacy of traditional Chinese medicine (TCM) therapies have increased, several empirical studies have shown that the quality of TCM trials are generally low in terms of risk of bias. This qualitative study aimed to investigate the factors influencing the quality of TCM clinical trials to provide strategic advice on trial quality improvement. Methods: One focus group with clinical trial auditors (n=4) and six indepth semi-structured interviews with clinical research organization managers (n=2), lecturers and researchers in TCM academic institutions (n=2), a chief physician in a TCM oncology department and a PhD candidate specialized in non-pharmaceutical TCM interventions were conducted. The interviews were audio-recorded, transcribed verbatim and thematically analyzed. Results: Factors that influenced the quality of TCM clinical trials merged on the following 6 themes: trial design; trialists/ participants; trial conducting; TCM specified problems; trial monitoring, and finally societal influences. The lack of expertise and time inputs of the trialists were repeatedly mentioned. Methodological difficulties experienced when conducting TCM trials included calculating sample size, analyzing the efficacy of TCM decoctions with multiple ingredients, blinding in trials investigating non-pharmaceutical TCM interventions were highlighted. Interviewees agreed that third-party monitoring can help improving trial quality and improved participant welfare and may accelerate recruiting processes and increase compliance; however more comprehensive regulations and funding requirements would be needed. Conclusions: This study identified real-life issues influencing the quality of TCM clinical trials from design to reporting. In addition to mandatory training for TCM trial designers and coordinators, more effective institutional oversight is required. Future studies should explore specific measures to address the methodological problems in TCM trials and explore how the quality of TCM trials can affect further evidence synthesis and clinical practice